Phase 1/2 Study of VIP152, Venetoclax, and Prednisone (VVIP) in Relapsed/Refractory Lymphoid Malignancies
Phase: PHASE1
Conditions: Lymphoma, Non-Hodgkin Lymphoma, NHL, Hematologic Malignancies, Lymphoid Malignancies
Sponsor: National Cancer Institute (NCI)

Abbreviated Title:  VVIP in R/R NHL
Version Date:   11/20/2025
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Abbreviated Title: VVIP in R/R NHL
NIH Protocol #: 000633
Version Date: 11/20/2025
NCT Number: NCT05371054 
Title: Phase 1/2 Study of VIP152, Venetoclax, and Prednisone (VVIP) in 
Relapsed/Refractory Lymphoid Malignancies
NCI Principal Investigator:
Christopher Melani, M.D.
Lymphoid Malignancies Branch (LYMB) Center for Cancer 
Research (CCR) National Cancer Institute (NCI)
National Institutes of Health (NIH) Building 10, Room 
4N115 Bethesda, MD 20892
Phone: 240-760-6057
Email: Christopher.melani@nih.gov
Drug/Device 
Name:
VIP152
venetoclax
prednisone
Vysis LSI MYC Break Apart 
Rearrangement Probe Kit
IND/IDE 
Number:
160533
NSR Device
Sponsor:
Center for Cancer Research, NCI
Manufacturer:
Vincerx, Inc.
AbbVie Inc
generic
Abbott Molecular Inc.
Supplier:
Vincerx, Inc.
CC Pharmacy
CC Pharmacy
Laboratory of Pathology, NCI

Abbreviated Title:  VVIP in R/R NHL
Version Date:   11/20/2025
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PRÉCIS
Background:
•
High unmet medical need for relapsed/refractory non-Hodgkin lymphoma (NHL) after 
exhausting chemotherapy and/or chemo-immunotherapy regimens
•
Targeted therapies aimed at disrupting cell death pathway in hematologic malignancies 
are emerging and showing significant activity in both the relapsed and first-line settings
•
VIP152 is a selective inhibitor of PTEFb/CDK9 and is expected to show efficacy in 
tumor indications that overexpress MYC and MCL-1. VIP152 monotherapy has 
demonstrated a mild toxicity profile and preliminary efficacy in Phase 1 studies in 
advanced cancer
•
The combination of VIP152 with venetoclax and prednisone (VVIP) targets major cell-
death pathways in lymphoid malignancies (BCL-2 and MCL-1) and may overcome 
chemo-resistance and/or single drug resistance to venetoclax
Objectives:
•
Phase 1: To determine the maximum tolerated dose (MTD), recommended Phase 2 dose 
(RP2D), and the safety and toxicity profile of the combination of VIP152 with venetoclax 
and prednisone (VVIP) in relapsed/refractory lymphoid malignancies
•
Phase 2: To determine the complete response (CR) rate of the combination of VIP152 
with venetoclax and prednisone (VVIP) in R/R lymphoid malignancies
Eligibility:
•
Individuals  ≥ 18 years of age
•
ECOG performance status of ≤ 2
•
Histologically or cytologically confirmed relapsed and/or refractory NHL
•
Adequate organ function unless dysfunction secondary to disease effect
Design:
•
Open-label, single-center, non-randomized Phase 1/2 study
•
Phase 1: Standard “3 + 3” design will be used to determine the MTD and RP2D of dose-
escalated VIP152 and venetoclax with fixed dose prednisone in relapsed/refractory 
lymphoid malignancies
•
Phase 2: Expansion cohorts of defined aggressive NHL subtypes will be treated at the 
RP2D to determine the ORR and CR rate in these disease groups
•
Up to 24 cycles of combination targeted therapy given in 21-day cycles with the option to 
stop therapy after 12 cycles if in CR following cycles 6 and/or 12 of therapy.
•
To explore all dose levels of VIP152 and venetoclax in combination prednisone (VVIP) 
in R/R NHL in the Phase 1 study (24 participants max) and to assess the CR rate in 3 
defined cohorts of aggressive NHL in a Phase 2 dose expansion (3 cohorts x 29 
participants = 87 participants max) at RP2D, the accrual ceiling will be set at 130 
participants. 

Abbreviated Title:  VVIP in R/R NHL
Version Date:   11/20/2025
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TABLE OF CONTENTS
PRÉCIS...........................................................................................................................................2
TABLE OF CONTENTS ................................................................................................................3
STATEMENT OF COMPLIANCE ................................................................................................6
1
INTRODUCTION ...................................................................................................................6
1.1
Study Objectives............................................................................................................6
1.2
Background and Rationale.............................................................................................7
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT .......................................................15
2.1
Eligibility Criteria........................................................................................................15
2.2
Screening Evaluation...................................................................................................19
2.3
Participant Registration and Status Update Procedures ..............................................21
2.4
Baseline Evaluation.....................................................................................................22
3
STUDY IMPLEMENTATION .............................................................................................22
3.1
Study Design ...............................................................................................................22
3.2
Drug Administration....................................................................................................26
3.3
Dose Modifications......................................................................................................26
3.4
On Study Assessments/Evaluations.............................................................................31
3.5
Study Calendar ............................................................................................................36
3.6
Cost and Compensation...............................................................................................41
3.7
Criteria for Removal from Protocol Therapy and Off Study Criteria ..........................41
4
CONCOMITANT MEDICATIONS/MEASURES...............................................................42
4.1
Permitted Therapy .......................................................................................................43
4.2
Concomitant Medications to Be Used with Caution.....................................................46
4.3
Prohibited Therapy ......................................................................................................48
5
CORRELATIVE STUDIES FOR RESEARCH....................................................................49
5.1
Biospecimen Collection...............................................................................................49
5.2
Sample Collection, Processing and Analyses ..............................................................50
5.3
Sample Storage, Tracking and Disposition .................................................................54
5.4
Samples for Genetic/Genomic Analysis......................................................................57
6
DATA COLLECTION AND EVALUATION......................................................................57
6.1
Data Collection ............................................................................................................57
6.2
Data Sharing Plans.......................................................................................................58
6.3
Response Criteria.........................................................................................................59
6.4
Toxicity Criteria ..........................................................................................................60
7
NIH REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING PLAN.....60
7.1
Definitions ...................................................................................................................60
7.2
OHSRP Office of Compliance and Training / IRB Reporting......................................60
7.3
NCI Clinical Director Reporting..................................................................................60

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7.4
NIH Required Data and Safety Monitoring Plan..........................................................60
8
SPONSOR SAFETY REPORTING......................................................................................61
8.1
Definitions ...................................................................................................................61
8.2
Assessment of Safety Events.......................................................................................62
8.3
Reporting of Serious Adverse Events..........................................................................62
8.4
Waiver of Expedited Reporting to CCR.......................................................................63
8.5
Safety Reporting Criteria to the Pharmaceutical Collaborators...................................63
8.6
Reporting Pregnancy....................................................................................................63
8.7
Regulatory Reporting for Studies Conducted Under CCR-Sponsored IND ...............64
8.8
Sponsor Protocol Deviation Reporting........................................................................64
9
CLINICAL MONITORING..................................................................................................64
10
STATISTICAL CONSIDERATIONS ...............................................................................65
10.1
Objectives and Endpoints............................................................................................65
10.2
Sample Size Determination .........................................................................................67
10.3
Populations for Analyses.............................................................................................69
10.4
Statistical Analyses......................................................................................................69
11
COLLABORATIVE AGREEMENTS...............................................................................71
11.1
Cooperative Research and Development Agreement..................................................71
12
HUMAN SUBJECTS PROTECTIONS.............................................................................72
12.1
Rationale For Participant Selection.............................................................................72
12.2
Participation of Children .............................................................................................72
12.3
Risk/Benefit Assessment.............................................................................................72
12.4
Consent Process and Documentation ..........................................................................74
13
REGULATORY AND OPERATIONAL CONSIDERATIONS.......................................75
13.1
Study Discontinuation and Closure.............................................................................75
13.2
Quality Assurance and Quality Control.......................................................................76
13.3
Conflict of Interest Policy............................................................................................76
13.4
Confidentiality and Privacy.........................................................................................76
14
PHARMACEUTICAL INFORMATION/ DEVICE INFORMATION.............................77
14.1
Venetoclax...................................................................................................................77
14.2
Prednisone ...................................................................................................................78
14.3
VIP152.........................................................................................................................79
14.4
Additional Information................................................................................................79
14.5
Vysis LSI MYC Break Apart Rearrangement Probe Kit ............................................80
15
REFERENCES ...................................................................................................................81
16
ABBREVIATIONS ............................................................................................................84
17
APPENDIX.........................................................................................................................87
17.1
Appendix A: Performance Status Criteria...................................................................87

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17.2
Appendix B: Inhibitors and Inducers of CYP3A.........................................................88
17.3
Appendix C: Electrolyte Imbalances Management and Tumor Lysis Syndrome 
Prevention..................................................................................................................................89
17.4
Appendix D: Lugano Classification Criteria...............................................................93
17.5
Appendix E: Study Drug Diary ...................................................................................95

Abbreviated Title:  VVIP in R/R NHL
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STATEMENT OF COMPLIANCE
The trial will be carried out in accordance with International Council for Harmonisation Good 
Clinical Practice (ICH GCP) and the following: 
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812) 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training.
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; an 
IRB determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form.
1
INTRODUCTION
1.1
STUDY OBJECTIVES
1.1.1
Primary Objective
•
Phase 1: To determine the MTD, RP2D, and the safety and toxicity profile of the 
combination 
of 
VIP152 
with 
venetoclax 
and 
prednisone 
(VVIP) 
in 
relapsed/refractory lymphoid malignancies
•
Phase 2: To determine the complete response (CR) rate of the combination of VIP152 
with venetoclax and prednisone (VVIP) in R/R lymphoid malignancies
1.1.2
Secondary Objective
•
To assess the activity (overall response rate (ORR), time to response [TTR], duration 
of response [DOR], event-free survival [EFS], progression-free survival [PFS] and 
overall survival [OS]) of VIP152 in combination with venetoclax and prednisone 
(VVIP) in relapsed/refractory lymphoid malignancies
1.1.3
Exploratory Objectives
•
To assess the ORR and CR rate to VVIP rechallenge in participants who achieve CR, 
discontinue therapy after 12 cycles and subsequently relapse more than 6 months after 
initial study drug discontinuation
•
To assess circulating tumor DNA (ctDNA) response and correlate with molecular 
tumor analysis
•
To evaluate biomarkers of sensitivity or resistance to VIP152, venetoclax and 
prednisone
•
To assess the pharmacokinetics and pharmacogenomics of VIP152, venetoclax, and 
prednisone when given in combination

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1.2
BACKGROUND AND RATIONALE
1.2.1
Disease background
Relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) remain incurable and represent a high 
unmet medical need. 
1.2.1.1
Diffuse large B-cell lymphoma (DLBCL)
DLBCL is the most common aggressive B-cell non-Hodgkin lymphoma (NHL), accounting for 
30–40% of B-cell lymphoma in the United States. Although much progress has been made since 
the advent of chemoimmunotherapy, patients with relapsed or refractory DLBCL have limited 
treatment options and an overall poor prognosis. 
Based on gene expression profiling (GEP) studies, DLBCL can be classified based on the cell of 
origin (COO) into two major groups: germinal center B-cell (GCB) subtype, and the activated B-
cell (ABC) subtype. Approximately 15%–20% do not fit into these two categories, and therefore, 
are molecularly unclassifiable. Different immunohistochemistry (IHC) methods are also used to 
classify DLBCL based on the COO. The most widely used algorithm is based on publication by 
Hans et al. (1), which evaluates the expression of 3 cellular proteins: CD10, BCL6, and 
MUM1/IRF4. Using this algorithm, DLBCL is classified as GCB or non-GCB. In general, DLBCL 
of the non-GCB subtype is associated with an unfavorable outcome when treated with standard R-
CHOP chemotherapy regardless of how they are defined. 
In addition to the COO, recent genetic and proteomics studies identified a prognostic role for MYC 
and BCL2 genetic translocations and/or protein co-expression. Approximately 10% of diffuse 
large B-cell lymphomas (DLBCLs) harbor an MYC oncogene rearrangement (MYC+). MYC 
rearrangement was associated with significantly worse overall survival, especially for the cases 
with GCB phenotype (2-4). Earlier studies using fluorescent in situ hybridization (FISH) reported 
that 7% to 10% of DLBCL harbored MYC, BLC2 and/or BCL6 translocations, and were called 
“double hit” lymphoma (DHL), or triple hit lymphoma. In the most recent World Health 
Organization (WHO) revision of lymphoma classification, this category is now recognized as 
“high grade B-cell lymphoma (HGBCL) with rearrangements of MYC and BCL2 and/or BCL6”. 
The vast majority of the cases of DLBCL with DH genetics are observed in the GCB subtype. The 
aggressive clinical course and poor response to therapy seen with DHL is in direct contrast to the 
favorable prognosis typically associated with GCB subtype. 
Front-line combination chemo-immunotherapy regimens such as R-CHOP or dose-adjusted 
EPOCH-R can cure approximately 65-70% of patients with DLBCL (5). Additionally, in a 
prospective study of dose-adjusted EPOCH-R in patients with MYC-rearranged DLBCL or DHL, 
approximately 71% of patients were cured with front-line DA-EPOCH-R chemo-immunotherapy 
(6). Standard therapy for relapsed/refractory disease often includes salvage chemotherapy 
followed by autologous stem cell transplant (ASCT), but less than 20% of patients achieve durable 
remission with this treatment approach, especially those who have received prior rituximab therapy 
and those who relapse within 12 months of diagnosis (7). Chemotherapy refractory patients and 
those with early relapse following ASCT have a dismal prognosis with an ORR and CR rate of 
26% and 7%, respectively, to next line of therapy and a median survival of only 6.3 months (8). 
Anti-CD19 CAR-T therapy has been shown to result in durable remission in approximately 30-
40% of these chemotherapy-refractory patients but can be associated with significant cost and 
toxicity and is not readily available or accessible for all patients (9, 10). Novel treatment options 
are desperately needed to improve outcome in these poor-risk patients.

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1.2.1.2
Peripheral T-cell lymphoma (PTCL)
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of rare neoplasms counted among 
the mature T-cell malignancies (TCM), and accounts for 5-10% of all lymphomas. Currently, the 
World Health Organization (WHO) classification combines mature T- and NK-cell neoplasms 
under the umbrella term PTCL and the category is composed of 24 different entities, based on the 
different morphologic, phenotypic, molecular, and clinical features, including disease site (11). 
Compared with B-cell lymphomas, many types of PTCL develop not in lymph nodes, but in 
specific extranodal sites such as extranodal NK/T cell lymphoma, nasal type (ENKL) in the nasal 
cavity, enteropathy-associated T-cell lymphoma (EATL) in the small intestine and hepatosplenic 
T-cell lymphoma (HSTL) in the liver and spleen. The most common histologic subtype is 
peripheral 
T-cell 
lymphoma, 
not 
otherwise 
specified 
(PTCL-NOS), 
followed 
by 
angioimmunoblastic T-cell lymphoma (AITL) or anaplastic large cell lymphoma (ALCL), either 
ALK positive (ALK+) or ALK negative (ALK-) and these three types account for about 60% of 
all cases of PTCLs (12); however, it is still rare and the age-adjusted incidence in the U.S. for 
PTCL-NOS, AITL and ALCL is 0.30, 0.05 and 0.25 per 100,000 person-years, respectively (13-
15).
The presentation of patients with PTCL largely depends on the subtype. PTCL-NOS, AITL, and 
ALCL often present with generalized lymphadenopathy, and there is also frequent involvement of 
the skin, gastrointestinal tract, liver, spleen, and bone marrow. In contrast, a number of rare specific 
subtypes, such as ENKL, HSTL, and EATL, present primarily with extranodal disease, and other 
subtypes, such as adult T-cell leukemia (ATL) and T prolymphocytic leukemia (T-PLL), may have 
a leukemic presentation. Advanced stage disease (stages III and IV) is common: PTCL-NOS 69%, 
AITL 89%, ALK+ALCL 65%, ALK-ALCL 58%, EATL 69%, HSTL 90%. 
Although front-line anthracycline-containing chemotherapy can cure approximately 36-60% of 
patients with ALCL, durable remission with such therapy is achieved in less than 1/3 of patients 
diagnosed with other subtypes of PTCL (12). In previously untreated CD30+ PTCL, the addition 
of brentuximab to CHP chemotherapy improved median progression-free survival over CHOP 
(48.2m vs 20.8m, p=0.0110) and has become a standard up-front treatment approach for CD30+ 
tumors (16). Although chemotherapy remains the standard front-line treatment for PTCL, a 
majority of patients will relapse following or are refractory to treatment and require additional 
therapy.
Since 2009, the U.S. Food and Drug Administration approved several drugs with novel 
mechanisms of action for the treatment of patients with recurrent PTCL); these included 
pralatrexate in 2009, brentuximab vedotin (BV) for ALCL in 2011, romidepsin in 2011, and 
belinostat in 2014. With the exception of BV, all of the approvals were based on response rates 
without demonstration of survival benefit, even though the response rates were less than 30% and 
any survival benefit is yet to be demonstrated. MD Anderson Cancer Center retrospectively 
analyzed 321 patients with PTCL-NOS and AITL and found that the median PFS after pralatrexate 
and romidepsin as single agents were 3.0 and 2.5 months respectively, which was not significantly 
different from chemotherapy approach (14). A meta-analysis of available treatments for 
relapsed/refractory PTCL showed that even though approved, belinostat and pralatrexate have 
lower safety than several other regimens (17). New therapeutic approaches with higher efficacy 
and better safety profile are therefore needed.

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1.2.1.3
Disease background summary
In summary, while significant advances in the cure of aggressive B-cell malignancies have 
occurred in the past decades, R/R DLBCL of above-mentioned COO or molecular subtype and 
R/R PTCL represent patient populations with highly unmet medical need. Identification of key 
survival pathways in lymphoid malignancies and development of drugs that target those pathways 
have resulted in recent therapeutic advances. Whereas chemo-immunotherapy combinations are 
empirically driven- as cytotoxic drugs do not target specific pathogenetic pathways- 
mechanistically based combinations of targeted agents will likely further leverage their benefits. 
Insights into the molecular pathogenesis of these tumor types have identified abnormalities in key 
survival pathways. Regulation of apoptosis by BCL-2 family proteins is a central regulator of 
normal B and T cells and lymphoid tumors have acquired multiple mechanisms of deregulation 
including translocation, amplification, and elevated gene expression from loss of endogenous 
MiRs that repress BCL-2, BCL-XL and MCL-1 expression and gene hypomethylation. 
1.2.2
Drug background
1.2.2.1
Venetoclax
Venetoclax (GDC-0199, ABT-199, A-1195425.0, or RO5537382) is a selective, orally 
bioavailable, small-molecule Bcl-2 family protein inhibitor being developed by AbbVie and 
Roche/Genentech for oncology and immunology indications. In vitro, venetoclax demonstrated 
cell-killing activity against patient-derived CLL and acute myeloid leukemia (AML) cells and a 
variety of lymphoma and leukemia cell lines, including B-cell FL, mantle cell lymphoma (MCL), 
DLBCL, and multiple myeloma (MM). Venetoclax was especially potent against NHL cell lines 
expressing high levels of Bcl-2. Leukemia and lymphoma cell lines bearing the t(14;18) 
translocation were significantly more sensitive to venetoclax than non-mutated lines.
Venetoclax is currently undergoing evaluation in NHL and MM and is approved as monotherapy 
or in combination with rituximab or obinutuzumab for the treatment of CLL/small lymphocytic 
lymphoma (SLL) and is approved in combination with azacytidine, decitabine or low-dose 
cytarabine in older individuals with AML. Rapid reductions of peripheral lymphocytes and 
lymphoid masses observed after initial dosing with venetoclax has provided support for 
evaluation of a non-chemotherapy combination treatment regimen as well as for future 
combinations with myelosuppressive chemotherapy as part of the overall clinical development 
plan. Venetoclax is also undergoing evaluation in systemic lupus erythematosus.
For detailed information of Venetoclax clinical data please refer to venetoclax prescribing 
information. 
1.2.2.1.1 Safety of Venetoclax
A total of 106 patients with relapsed or refractory NHL were treated with venetoclax 200 to 1200 
mg daily in dose-escalation and safety expansion cohorts of a phase 1 study (18). Venetoclax 
monotherapy was overall well tolerated with no clinical TLS observed and 3 patients with 
laboratory evidence of TLS only. Treatment-emergent adverse events (AEs) were reported in 103 
(97%) patients, most being grade 1-2 in severity. Grade 3-4 AEs occurred in 59 (56%) patients, 
most commonly hematologic, including anemia (15%), neutropenia (11%), and thrombocytopenia 
(9%).  Less common grade 3-4 AEs included fatigue (7%), diarrhea (3%), constipation (2%), 
decreased appetite (1%), cough (1%), back pain (1%), and URI (1%).
1.2.2.1.2 Efficacy of Venetoclax monotherapy

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A phase 1 trial of venetoclax monotherapy was performed in 106 patients with relapsed and or 
refractory NHL. In 34 patients with DLBCL, ORR was 18% with CR rate of 12% and a median 
PFS of only 1 month (18). Venetoclax 1200 mg daily was determined to be the recommended 
single-agent dose for future studies in FL and DLBCL, with 800 mg being sufficient to consistently 
achieve durable response in patients with MCL.
1.2.2.2
VIP152
VIP152, previously known as BAY 1251152, is a potent and selective inhibitor of positive 
transcription elongation factor b (PTEFb) / cyclin-dependent kinase 9 (CDK9). CDK9 is the key 
factor regulating eukaryotic messenger ribonucleic acid (mRNA) transcription at the level of 
elongation. Cyclin-dependent kinases (CDKs) belong to a family of serine / threonine kinases, 
which associate with an activating cyclin regulatory sub-unit. Cell cycle CDKs (CDK1, CDK2, 
CDK4, and CDK6) are required for the correct timing and order of the events of the cell division 
cycle, whereas several non-cell cycle CDKs, including CDK9, have been shown to be involved in 
gene transcription. De-regulated CDK activity results in loss of cell cycle checkpoint function and 
increased expression of anti-apoptotic proteins, which has been directly linked to the molecular 
pathology of cancer.  CDK9 has been shown to have several binding partners including cyclin T1, 
cyclin T2, and cyclin K.   CDK9 and cyclin T1 form the PTEFb complex that is essential to mRNA 
elongation. 
Selective PTEFb inhibition is expected to show efficacy in tumor indications, which exhibit 
increased activity of PTEFb due to upstream alterations or those that are addicted to transcription 
of short-lived RNAs encoding for anti-apoptotic survival proteins downstream of PTEFb, like 
MYC, MCL1 (myeloid cell leukemia 1 protein), and CCND1 (cyclin D1). VIP152 has exhibited 
convincing single agent in vivo antitumor efficacy and good tolerability in c-myc amplified models 
of TNBC and gastric cancer in mice and partial or complete remissions in various models of AML, 
DLBCL and multiple myeloma (MM) in mice and rats (19). Other inhibitors of CDK9 have shown 
similar in vitro and in vivo activity across various ABC and GCB DLBCL cell lines and xenografts 
as well as in DLBCL cell lines with elevated MYC expression (20). Also, non-GCB DLBCL is 
more commonly associated with high MCL1 expression and frequent co-expression of MCL1 and 
BCL2 is seen in DLBCL cell lines suggesting that therapeutic strategies that target only one will 
lead to treatment failure due to compensatory upregulation of the other (21). Based on these data, 
VIP152 is planned to be developed as an innovative, novel treatment of select solid cancers and 
hematologic malignancy, which may be dependent on MYC, MCL1, and CCND1.  For more 
information in the preclinical results of VIP152 refer to the IB. 
1.2.2.2.1 Safety of VIP152
Safety for VIP152 is based on clinical experience in completed and ongoing studies (22, 23).  In 
Study VNC-152-101, a total of 37 subjects were evaluated at five VIP152 dose levels (5, 10, 15, 
22.5, and 30 mg). The MTD for this study was declared as 30 mg; neutropenia was the dose-
limiting toxicity. Data for 21 subjects are available at 4 dose levels (5, 10, 20 and 30 mg) in the 
clinically complete Study 18117. VIP152 was well tolerated, and AEs were relatively mild.  No 
MTD was determined for Study 18117.
The most commonly reported toxicities were neutropenia and gastrointestinal toxicity. The 
observed toxicity seen so far has been manageable with anti-emetics and G-CSF.  Administration 
of G-CSF has led to a fast recovery of neutropenia in all treated patients.

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Based on the pooled analysis of both studies (VNC-152-101 and 18117), the most commonly 
reported drug-related treatment-emergent adverse events (>20% of subjects) were nausea (58.6%), 
vomiting (39.7%) and neutropenia (20.7%). In >10% of subjects, anemia, diarrhea, and fatigue 
were observed.
In Study VNC-152-101, the most commonly (occurring in >10% of subjects) reported drug-related 
treatment-emergent adverse event (TEAEs) were nausea (70.3%), vomiting (48.6%) neutropenia 
(35.1%), fatigue (21.6%), anemia (18.9%), and diarrhea (16.2%). In Study 18117, the most 
commonly reported drug-related TEAEs (occurring in >10% of subjects) were nausea (38.1%), 
vomiting (23.8%), and fatigue (14.3%).
To date, no tumor lysis syndrome or cytokine release syndrome has been reported in patients with 
AML, NHL or solid tumors who have received VIP152. No drug-related deaths have been reported 
for VIP152 to date.
1.2.3
Preclinical synergy with VIP152 and venetoclax
Preclinical synergy has been demonstrated with another CDK9 inhibitor (BAY 114-3572) which 
possesses similar selectivity to VIP152 in combination with venetoclax (ABT-199).  In this SU-
DH-10 cell line xenograft in vivo mouse model, the tumor cells are resistant to venetoclax (ABT-
199) alone, while combination with the CDK9 inhibitor (BAY 114-3572), shows complete tumor 
regression (Figure 1).

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Figure 1
Other inhibitors of CDK9, such as AZD4573, have shown similar in vitro and in vivo activity with 
the combination of CDK9 inhibitors with the BCL2 inhibitor ventoclax in DLBCL cell lines and 
xenograft models (24).  Furthermore, inhibition of MCL1 with agents such as AZD5991 in 
addition to treatment with BH3 mimetics such as venetoclax and navitoclax have also 
demonstrated in vitro and in vivo activity across a number of PTCL cell lines and xenografts, 
suggesting a potential therapeutic benefit for combination therapy simultaneously targeting both 
pathways (25).
1.2.4
Preclinical synergy with venetoclax and prednisone
Prednisone has been included in this study as well as other combination targeted therapy studies 
(i.e., ViPOR) as an inducer of genotoxic stress to the lymphoma cells. In vitro data in DLBCL cell 
lines supports this concept showing significant synergy (as measured by %Response or Bliss) 
with the combination of corticosteroids and targeted agents such as venetoclax (Figure 2).

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Figure 2
1.2.5
Justification of dosing
A major limiting factor for targeted therapy is the need for long-term continuous dosing schedules, 
which precludes the ability to give multiple agents at once due to overlapping toxicities. Recent 

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combination targeted therapy studies have utilized an intermittent dosing strategy and/or fixed 
duration schedule in order to maximize efficacy as well as reduce potential toxicity.
An ongoing phase 1b/2 study of ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, and 
lenalidomide) is being conducted at the NCI with preliminary safety and efficacy demonstrated in 
patients with relapsed and/or refractory B-cell non-Hodgkin lymphomas (26). A phase I “3+3” 
design was used to determine the maximum tolerated dose (MTD) of 4 dose-levels (DLs) of dose-
escalated venetoclax (200mg, 400mg, 600mg, and 800mg) PO D2-14 (starts cycle 2 for DL1) in 
combination with fixed-dose ibrutinib 560mg PO D1-14, prednisone 100mg PO D1-7, 
obinutuzumab 1000mg IV D1-2, and lenalidomide 15mg PO D1-14. A phase II expansion in R/R 
DLBCL and FL was included at the MTD. Up to 6 cycles of ViPOR every 21-days was given 
without maintenance or consolidation. A single dose-limiting toxicity (DLT) of G3 intracranial 
hemorrhage occurred at DL1 with concomitant enoxaparin and ASA. No other DLTs occurred and 
venetoclax 800mg was used in expansion. Hematologic AEs (% cycles) were most common and 
included thrombocytopenia (23%), neutropenia (23%) and anemia (7%). G-CSF was used in 92% 
of pts and 89% of cycles with only 3 (6%) cases of febrile neutropenia. Non-hematologic AEs (% 
pts) were mainly G1-2 and included diarrhea (67%), hypokalemia (56%), nausea (52%), and rash 
(42%). Most common G3-4 non-hematologic AEs included hypokalemia (19%), diarrhea (8%), 
and a.fib/flutter (6%). G4 TLS occurred in 1 patient with HGBCL after the first venetoclax dose 
and was successfully treated without further TLS upon continued treatment. Dose reductions and 
delays occurred in only 8% and 9% of cycles, respectively. Tumor reduction occurred in 90% of 
patients overall with responses observed across all DLs and NHL subtypes. In all evaluable 
patients, ORR was 70% with 49% CR; including an ORR of 56% with 37% CR in aggressive NHL 
and an ORR of 94% with 69% CR in indolent NHL. Despite the intermittent, fixed-duration dosing 
of all study agents, 25 (69%) of 36 responses remained ongoing at the time of presentation.
Venetoclax as monotherapy or in combination with anti-CD20 antibody therapy is FDA-approved 
for use in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) 
using a 5-week ramp-up schedule from an initial dose of 20 mg daily to a maximum dose of 400 
mg daily. This 5-week ramp-up schedule; however, has been shown to be unnecessary in other 
lymphoid malignancies with a lower risk of TLS development. The phase Ib/II CAVALLI study 
assessed the combination of venetoclax with R-CHOP or G-CHOP in patients with B-cell NHL 
and DLBCL(27). In the dose finding phase I portion of the study, venetoclax at doses ranging from 
200 to 800 mg (without initial ramp-up) in 4 cohorts were tested in combination with R-CHOP 
and G-CHOP and the MTD was not reached and thus 800 mg was taken forward to the phase II 
portion of the study. Due to greater than expected hematologic toxicity, the continuous daily 
dosing regimen starting at day 3 was modified after cohort 1 (200 mg of venetoclax) to a non-
continuous 10-day dosing schedule using venetoclax (400 mg, 600 mg, and 800 mg) on days 4-10 
of cycle 1 and days 1-10 of cycles 2-8.
Given the safety and efficacy shown with time-limited, cyclic dosing of targeted agents as well as 
fixed venetoclax dosing without ramp-up in several lymphoid malignancies including DLBCL, 2 
dose levels of venetoclax (600mg and 800mg) daily given days 1 through 10 in 21-day cycles will 
be utilized in this phase 1/2 study in combination with VIP152.  Weekly dosing of VIP152 in 3 
dose levels (15mg, 22.5mg, and 30mg) will be given IV on days 2 and 9 of each 21-day cycle as 
weekly IV dosing was shown to be safe in the phase 1 monotherapy study (22).

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1.2.6
Rationale for combination
Given the pathogenesis and preclinical/clinical data available, we hypothesize that inhibiting 
multiple pathogenic survival pathways will leverage the efficacy of targeted agents in lymphoid 
malignancies and may overcome single agent resistance of BH3 mimetics. Combining venetoclax 
and VIP152 may provide a chemotherapy-sparing option to patients with certain lymphoid 
malignancies. Strong scientific rationale supports combined treatment with venetoclax and 
VIP152, as the two agents may have complementary activity that target different cellular proteins 
expressed on malignant lymphoid cells. Both agents have demonstrated potent reductions of 
malignant B cells after single- agent administration in early phase clinical studies in R/R DLBCL. 
Venetoclax has been associated with laboratory and clinical TLS, as well as neutropenia and 
thrombocytopenia. VIP152, in early phase 1 studies, has been associated with neutropenia. Such 
cell-killing effects are familiar to oncologists, and intensive management measures have been 
incorporated into the combination studies, including prophylactic treatment to prevent or reduce 
the severity of effects, adjustment of initial dose and schedule, and careful monitoring. In this 
combination study, prednisone will be given as another mechanism of genotoxic stress and 
granulocyte-colony-stimulating factor (G-CSF) will be included to mitigate the overlapping risk 
of neutropenia. Also, a major limiting factor for targeted therapy is the need for long-term 
continuous dosing schedules, which will likely preclude the ability to give multiple agents at once. 
Thus, intermittent dosing will almost certainly be necessary. Indeed, if these targeted agents 
undermine multiple essential survival mechanisms in the tumor cells and retard the emergence of 
resistance, combination targeted treatment may significantly improve the outcome of lymphoid 
malignancies. 
The overlapping toxicities of the regimen include hematologic toxicity, mainly neutropenia, and 
GI toxicity (i.e., nausea, vomiting, and diarrhea). These toxicities in monotherapy studies have 
generally been mild and manageable with G-CSF as well as anti-emetics and anti-diarrheals.  As 
this is a phase 1/2 study, the safety of the combination is not yet known and is being determined 
in the current protocol. The safety and toxicities of each individual agent when given as 
monotherapy is listed above.
Given the rationale and considerations above, we propose a Phase 1/2 study of VIP152 in 
combination with venetoclax and prednisone (VVIP) in relapsed/refractory lymphoid 
malignancies. The phase 1 portion of the study includes inter-patient dose escalation of VIP152 at 
3 dose levels (15 mg, 22.5 mg and 30 mg) and venetoclax at 2 dose levels (600mg and 800mg) in 
combination with fixed doses of prednisone in 21-day cycles. 
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT 
2.1
ELIGIBILITY CRITERIA
2.1.1
Inclusion Criteria
2.1.1.1
Participants must have a histologically or cytologically confirmed lymphoid malignancy 
as listed below, confirmed by the Laboratory of Pathology, NCI, as follows:
•
R/R MYC-rearranged DLBCL/HGBCL (MYC aberration must be confirmed by 
NCI Laboratory of Pathology to enroll)
•
R/R non-GCB DLBCL without MYC-rearrangement (COO and non-MYC 

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16
aberration must be confirmed by NCI Laboratory of Pathology to enroll. COO 
determination at enrollment will utilize immunohistochemistry and Han’s 
algorithm (28))
•
R/R PTCL (PTCL-NOS, PTCL-TFH, follicular TCL, AITL, ATLL, ALK+ ALCL 
and ALK- ALCL per 2016 WHO classification)
2.1.1.2
Relapsed and/or refractory disease, as defined below: 
•
Aggressive B-cell lymphoma: relapsed after and/or refractory to at least 2 prior 
systemic therapies, 1 or more which includes an anthracycline and anti-CD20 
targeting agent 
•
PTCL: relapsed after and/or refractory to at least 2 prior systemic therapies, 1 or 
more which includes an anthracycline (and a brentuximab vedotin-containing 
regimen for participants with ALK+ or ALK- ALCL)
2.1.1.3
Must have evaluable disease by clinical exam (i.e., palpable lymphadenopathy, 
measurable skin lesions, etc.), laboratory assessment (i.e., disease involvement of bone 
marrow or peripheral blood by morphology, cytology or flow cytometry), and/or imaging 
(measurable lymph nodes, masses, or bony lesions on CT or MRI and/or evaluable FDG- 
avid lesions on PET). 
NOTE: Lesions that have been irradiated cannot be included in the tumor assessment 
unless unequivocal tumor progression has been documented in these lesions after 
radiation therapy.
2.1.1.4
Age >18 years
2.1.1.5
ECOG performance status <2 (see Appendix A).
2.1.1.6
Adequate organ and marrow function as defined below unless dysfunction is secondary to 
disease:
Absolute neutrophil count*
>1,000/mcL
Hemoglobin*
>8 g/dL
Platelets
>75,000/mcL
INR
<1.5 X institutional upper limit of normal (ULN) for 
participants not receiving therapeutic anticoagulation
PTT/aPTT
<1.5 X institutional ULN normal except if the aPTT is 
elevated because of a positive Lupus Anticoagulant
Total bilirubin**
<1.5 X institutional ULN (or <3 X institutional ULN for 
participants with documented Gilberts syndrome)
AST(SGOT)/ALT(SGPT)***
<2.5 X institutional ULN
Serum creatinine
< 2.0 mg/dL
OR
Creatinine clearance****
>40 mL/min/1.73 m2 for participants with creatinine levels 
above 2 mg/dL

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17
Cr Cl will be calculated with the use of the 24-hour creatinine clearance or modified 
Cockcroft-Gault equation (eCCR; with the use of ideal body mass [IBM] instead of mass):
(140  Age) x IBM (kg)  [0.85 if female] 
72 x serum creatinine (mg/dL)
*RBC transfusions and use of G-CSF will be allowed in order to meet eligibility parameters.
**Total bilirubin must be <3 X institutional ULN for eligibility even if secondary to disease.
***AST(SGOT)/ALT(SGPT) must be <5 X institutional ULN for eligibility even if secondary to 
disease.
****Creatinine clearance must be >30 mL/min for eligibility even if secondary to disease.
2.1.1.7
Negative serum or urine pregnancy test must be obtained within 7 days before the first 
dose of study drug in individuals of childbearing potential. Postmenopausal individuals 
as defined below, are allowed to enroll without a pregnancy test: 
•
Age >50 years with amenorrhea for at least 12 months or  
•
Age ≤50 years with 6 months of spontaneous amenorrhea and follicle stimulating 
hormone (FSH) level within postmenopausal range (>40 mIU/mL) OR 
•
Permanently 
sterilized 
(e.g., 
tubal 
occlusion, 
hysterectomy, 
bilateral 
salpingectomy, uterine ablation)
2.1.1.8
Individuals of reproductive potential must agree to use highly effective contraception 
when sexually active. This applies for the period between signing of the informed consent 
and 90 days after the last administration of study drug.
Highly effective contraception includes: 
•
Established use of oral, injected or implanted hormonal methods of contraception
•
Placement of certain intrauterine devices (IUD) or intrauterine systems (IUS) 
•
Hysterectomy, oophorectomy, salpingectomy or vasectomy of the partner 
(provided that partner is the sole sexual partner of the individual of childbearing 
potential trial participant and that the vasectomized partner has received medical 
assessment of the surgical success) 
In addition, participants must agree to use condoms.
2.1.1.9
Participants that are positive for hepatitis B core antibody (HBcAb), hepatitis B surface 
antigen (HBsAg), or hepatitis C antibody (HCVAb) must have a negative hepatitis B 
and/or C viral load by polymerase chain reaction (PCR), and agree to additional 
monitoring as listed in Section 4.1.7.
2.1.1.10 Ability of participant to understand and the willingness to sign a written informed consent 
document.
2.1.1.11 Nursing participants must be willing to discontinue nursing from study treatment 
initiation through 90 days after the last administration of study drug.
2.1.2
Exclusion Criteria
2.1.2.1
The following restrictions apply to current or prior anti-cancer treatment, prior to the first 
dose of study drug:
•
Participants who are actively receiving any other anti-cancer investigational agents.

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18
•
Any chemotherapy, targeted therapy, or anti-cancer antibodies within 2 weeks 
prior to the first dose of study drug
•
Radio- or toxin-immunoconjugates within 10 weeks prior to the first dose of 
study drug
•
Prior allogeneic stem cell (or other organ) transplant within 6 months or any 
evidence 
of 
active 
graft-versus-host 
disease 
or 
requirement 
for 
immunosuppressants within 28 days prior to first dose of study drug
•
Not recovered (i.e., ≤ Grade 1 or baseline) from adverse events due to 
previously administered anti-cancer treatment, surgery, or procedure. NOTE: 
Exceptions to this include events not considered to place the participant at 
unacceptable risk of participation in the opinion of the PI (e.g., alopecia).
2.1.2.2
Participants requiring the following agents within 14 days or 5 half-lives of the drug 
(whichever is shorter) prior to the first dose of venetoclax and VIP152 are excluded:
•
Strong CYP3A inhibitors (see Appendix B)
•
Strong CYP3A inducers (see Appendix B)
•
Moderate CYP3A inhibitors (dose-escalation cohort only)
•
Moderate CYP3A inducers (dose-escalation cohort only)
NOTE: Moderate CYP3A inhibitors and inducers should be used with caution 
(see Section 4.2) for participants in the dose-expansion cohorts and an alternative 
medication used, whenever possible.
2.1.2.3
Known allergy to both xanthine oxidase inhibitors and rasburicase; or, known hypersensitivity 
to any of the study drugs
2.1.2.4
Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection 
(excluding fungal infections of nail beds) at study enrollment, or any major episode of 
infection requiring treatment with IV antibiotics or hospitalization (relating to the 
completion of the course of antibiotics) within 2 weeks prior to first dose of study drug
2.1.2.5
HIV-positive participants 
2.1.2.6
Active CMV infection as determined by a positive CMV PCR
2.1.2.7
Active SARs-CoV-2 infection based on PCR assay; prior SARs-CoV-2 infection 
allowed if completely recovered from infection and negative PCR testing
2.1.2.8
Clinically significant history of liver disease, including viral or other hepatitis, current 
alcohol abuse, or cirrhosis; as well as active infection with HBV or HCV except as noted 
above in inclusion criteria 2.1.1.9
•
Participants with occult or prior HBV infection (defined as positive hepatitis B 
surface antigen (HBsAg) or positive hepatitis B core antibody (HBcAb)) may be 
included if HBV DNA is undetectable (i.e., “none detected” in copies/mL or IU/mL). 
These individuals must be willing to undergo HBV DNA testing during treatment 
and in surveillance for at least 12 months after completion of study therapy.
•
Participants who are positive for HCV antibody must be negative for HCV by 
polymerase chain reaction (PCR) to be eligible for study participation
2.1.2.9
Malabsorption syndrome or other condition that precludes enteral route of 

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administration
2.1.2.10 History of other active malignancy requiring therapy that could affect compliance with 
the protocol or interpretation of results
2.1.2.11 Symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
2.1.2.12 Left ventricular ejection fraction (LVEF) < 45%
2.1.2.13 Clinically relevant findings on electrocardiogram (ECG) such as a second- or third-degree 
AV block or prolongation of the QTc interval (Fridericia) over 470 msec (participants 
with AV block and pacemaker in place for >1 year and checked by a cardiologist within 
<6 months before the first dose of study drug, will not be excluded).
2.1.2.14 Uncontrolled intercurrent illness (including psychiatric) or social situations that may 
limit interpretation of results or that could increase risk to the participant
2.1.3
Recruitment Strategies
This protocol may be abstracted into a plain language announcement posted on NIH websites and 
on NIH social media platforms. Study participants will be recruited from the population of 
participants screened in the lymphoid malignancies clinic of the National Institutes of Health. 
These will include both referrals from outside physicians as well as participant self -referrals.
2.2
SCREENING EVALUATION
2.2.1
Screening activities performed prior to obtaining informed consent
Minimal risk activities that may be performed before the participant has signed a consent include 
the following: 
•
Email, written, in person or telephone communications with prospective participants 
•
Review of existing medical records to include H&P, laboratory studies, etc.  
•
Review of existing MRI, x-ray, or CT images
•
Review of existing photographs or videos
•
Review of existing pathology specimens/reports from a specimen obtained for diagnostic 
purposes
2.2.2
Screening activities performed after a consent for screening has been signed
The following activities will be performed only after the participant has signed the study consent 
or the consent for study 01-C-0129 (provided the procedure is permitted on that study) on which 
screening activities may also be performed. Assessments performed at outside facilities or on 
another NIH protocol within the timeframes below may also be used to determine eligibility once 
a participant has signed the consent unless otherwise specified below.
Assessments and procedures to confirm study eligibility should be completed within 28 days prior 
to the start of treatment unless otherwise indicated. See also the Section 3.5, Study Calendar.
2.2.2.1
Clinical Assessments
•
Medical history, including: diagnosis, treatment (e.g., systemic treatments, radiation 
and surgeries), status, and significant prior/ongoing side effects and symptoms
•
Physical examination, including: height (screening only), weight, vital signs (i.e., 
temperature, pulse, respiratory rate, and blood pressure), and assessment of 

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performance status using the ECOG scale
•
Review of concomitant medications
2.2.2.2
Laboratory Evaluations
•
CBC with differential- to assess bone marrow function.
•
Chemistry panels including: Acute Care Panel (Sodium (NA), Potassium (K), 
Chloride (CL) Total CO2 (Bicarbonate), Creatinine, Glucose, Urea nitrogen, eGFR); 
Mineral Panel (Albumin, Calcium, Magnesium, Phosphorus); Hepatic Panel 
(Alkaline Phosphatase, ALT/GPT, AST/GOT, Total Bilirubin, Direct Bilirubin); and 
24 -hour urine creatinine clearance (if needed to measure CrCl in cases where serum 
creatinine >2.0 mg/dl)- to assess organ function and rule-out active TLS.
•
Others: Lactic dehydrogenase (LDH) and Uric acid- to assess tumor burden and rule-
out active TLS.
•
Coagulation panel, including: PT/INR and aPTT- to assess liver synthetic function 
and rule out DIC.
•
Urinalysis- to rule out active infection and assess for underlying renal dysfunction.
•
CMV serology and PCR- to rule out active infection
•
SARs-CoV-2 PCR (All COVID testing will be done under an EUA)- to rule out active 
infection
•
HIV 1/2 antibody, Hepatitis B surface antigen (HBsAg), Hepatitis B surface antibody 
(HBsAb), Hepatitis B core antibody (HBcAb), and Hepatitis C antibody (HCVAb) 
(within 3 months)- to rule out active infection
o
Participants who are HBsAg positive or HBcAb positive are required to have 
viral load testing by HBV DNA PCR. If HBV DNA > 100 they are ineligible 
and should be referred to hepatology for HBV treatment prior to study 
enrollment. If HBV DNA < 100 they should have repeat testing approximately 
1-2 weeks later and if continued positivity should be referred to hepatology for 
HBV treatment prior to retesting for eligibility  (See Section 4.1.7).
o
Participants who are HCV Ab positive should have viral load check by HCV 
PCR. If HCV PCR positive they are ineligible and should be referred to 
hepatology for HCV treatment prior to retesting for eligibility.
•
Urine and/or serum HCG in individuals of childbearing potential. Note: Individuals 
of reproductive potential must agree to use highly effective contraception when 
sexually active. These methods should be documented in source documents. The 
investigator or a designated associate is requested to advise the participant on how to 
achieve highly effective birth control- to rule out active pregnancy
•
PTCL cohort only: T-cell receptor gene rearrangement (peripheral blood), HTLV-
I serology- to diagnosis PTCL
2.2.2.3
Imaging Studies
NOTE: Results from NIH only.
•
CT neck, chest, abdomen and pelvis (with IV and PO contrast unless contraindicated)
o
Lesions in other anatomic locations or locations that are not well visualized by 
the above listed CT may be measured at baseline by an alternative CT and/or 
MRI instead and should continue to be measured by CT and/or MRI until 

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disease progression.
o
In the case where CT with contrast is contraindicated, an alternative would be 
MRI of the abdomen and pelvis and CT of the chest and neck without contrast. 
In this case, neck nodes cannot be used as target lesions.
•
PET Imaging (i.e., whole body 18F-FDG PET/CT)
2.2.2.4
Other Assessments and Procedures
•
Pathologic review of archival sample for confirmation of diagnosis by Laboratory of 
Pathology, NCI (any time prior to enrollment). If the sample is not available, and 
there is an accessible tumor, a biopsy will be done to confirm the diagnosis.
•
Electrocardiogram (EKG)
•
ECHO for LVEF determination
2.3
PARTICIPANT REGISTRATION AND STATUS UPDATE PROCEDURES
Registration and status updates (e.g., when a participant is taken off protocol therapy and when a 
participant is taken off-study) will take place per CCR SOP ADCR-2, CCR Participant 
Registration & Status Updates found at: https://nih.sharepoint.com/sites/NCI-CCR-OCD-
Communications/SitePages/OEC-Administrative---Clinical-Research-(ADCR).aspx?Mode=Edit.
2.3.1
Screen Failures
A screen failure occurs when a participant who consents to participate in the clinical study is not 
subsequently treated on the protocol. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, and eligibility 
criteria.
Individuals who do not meet the criteria for participation in this trial (screen failure) because of a 
transient underlying condition not related to the condition under study may be rescreened once 
after the underlying condition has resolved.
2.3.2
Treatment Assignment and Randomization/Stratification Procedures
2.3.2.1
Cohorts
Number
Name
Description
1
Phase 1-Dose 
Escalation
Participants with either R/R MYC-rearranged 
DLBCL/HGBCL, R/R non-GCB DLBCL (no MYC 
rearrangement) and/or R/R PTCL  
2
Phase 2- R/R 
MYC-rearranged 
DLBCL/HGBCL
Participants with R/R MYC-rearranged DLBCL/HGBCL for 
Phase 2 dose expansion 
3
Phase 2-R/R 
non-GCB 
DLBCL
Participants with R/R non-GCB DLBCL (no MYC-
rearrangement) for Phase 2 dose expansion 
4
Phase 2-R/R 
PTCL
Participants with R/R PTCL for Phase 2 dose expansion 

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2.3.2.2
Arms
Number
Name
Description
1
Phase 1: Arm 1 
– Dose 
Escalation
VVIP-VIP152 and venetoclax at escalating doses with 
prednisone at fixed doses to determine the MTD and RP2D of 
VIP152 and venetoclax 
2
Phase 2: Arm 2 
– Dose 
Expansion
VVIP- VIP152 and venetoclax at the RP2D with prednisone at 
fixed doses 
2.3.2.3
Treatment Assignment
Participants in cohort 1 will be directly assigned to Arm 1. Participants in cohorts 2, 3, and 4 will 
be directly assigned to arm 2. 
2.4
BASELINE EVALUATION
The baseline evaluations should be performed within 28 days prior to the first dose of study drug 
unless otherwise noted; tests performed as part of screening do not need to be repeated if they were 
performed within the specified window. NOTE: See Study Calendar, Section 3.5 for details and 
tests required within 7 days of first dose of study drug.
It should be noted that some participants are admitted prior to the initiation of the first dose of 
venetoclax for prophylaxis for TLS (Section 4.1.3). In the event that labs are repeated after 
initiation of TLS prophylaxis and prior to drug, and any value(s) falls outside of the eligibility 
criteria (e.g., dilutional changes from hydration for TLS prophylaxis, etc.), the participant may still 
initiate treatment if it is determined that the change in value(s) is related to this intervention and 
documented in the records by the investigator.
3
STUDY IMPLEMENTATION
3.1
STUDY DESIGN
To determine the MTD, RP2D, and the safety and toxicity profile of VIP152 and venetoclax in 
combination with prednisone (VVIP) in relapsed/refractory NHL, a standard “3 + 3” design will 
be used to determine the MTD and RP2D of dose-escalated VIP152 and venetoclax with fixed dose 
prednisone in the phase 1 portion of the study. Phase 2 expansion cohorts of participants with 
relapsed/refractory aggressive NHL (3 different subgroups) will be treated at the RP2D for a 
further assessment of safety and efficacy. Transition from phase 1 to phase 2 will occur after 
interim analysis as described in section 10.4.6.1. 

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Combination targeted therapy will be given in cycles every 21 days:
•
VIP152 dose escalation in 3 dose levels (DL) IV on day 2 and day 9 (see dose levels 
below)
•
Venetoclax dose escalation in 2 dose levels (DL) by mouth daily days 1-10 (see dose 
levels below)
•
Prednisone 100 mg by mouth daily days 1-10
•
Pegfilgrastim 6 mg SQ one time dose on day 11 
Study treatment will continue as long as:
•
Participant is deriving clinical benefit (complete remission [CR], partial remission 
[PR], or stable disease [SD]) and
•
Participant is not experiencing any unacceptable toxicity
It is anticipated that treatment will be given primarily on an outpatient basis; however, treatment 
may be initiated as inpatient in participants at high-risk of tumor lysis syndrome (TLS). See section 
4.1.3 for details. Treatment may also be given on an inpatient basis for other reasons as clearly 
documented in the medical record (e.g., pre-planned decision for increased participant 
monitoring/follow-up, participant/scheduling convenience, etc.); see also Section 8.1.2.
Restaging CT scans will be performed after cycles 1 and 2 of therapy and then every other cycle 
as an early assessment of disease response to combination therapy.  Full disease restaging with 
CT, FDG-PET and bone marrow (as clinically indicated) will be performed following cycles 6 and 
12 of study therapy. Participants who achieve CR will stop study therapy after completion of cycle 
12 and will enter follow-up. These participants may be rechallenged with study therapy if relapse 
occurs ≥ 6 months after stopping study therapy (see Section 3.2.3). Participants who do not achieve 
such responses will continue therapy until disease progression (PD), unacceptable toxicity, or a 
maximum of 24 total cycles of therapy.
3.1.1
Dose Limiting Toxicity
A DLT (dose-limiting toxicity) is defined as a grade 3 or higher adverse event (AE) that occurs 
in the dose-escalation cohort within the first 22 days after initiation of VVIP (i.e., Cycle 1, Day 1 to 
Cycle 2, Day 1 pre-dose) and is considered related to study drug (i.e., VIP152, venetoclax, and/or 

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prednisone) or a treatment delay of cycle 2 of > 7 days for hematologic or non-hematologic 
toxicities with the following exceptions:
3.1.1.1
Non-Hematologic DLT exceptions to above  definition
•
Grade 3 nausea with maximum medical supportive care and persisting ≤ 7 days
•
Grade 3 vomiting or diarrhea if the participant does not require total parenteral nutrition 
(TPN) or tube feeding, and the toxicity improves to < grade 3 within 72 hours
•
Grade 3 fatigue persisting ≤ 7 days
•
Grade 3 fever or infection
•
Grade 3 rash or dry skin with maximum medical supportive care and persisting ≤ 7 days
•
Grade 3 hypo- or hypernatremia, hypo- or hyperkalemia, hypo- or hypercalcemia, hypo- 
or hypermagnesemia, and/or hypo- or hyperphosphatemia that improves to < grade 3 
within ≤ 7 days
•
Grade 3 atrial fibrillation that is adequately controlled with medical management
3.1.1.2
Hematologic DLT exceptions to above definition:
•
Grade 3 febrile neutropenia (ANC <1000/mm3 with a temperature of >38.3°C [single] or 
≥38°C [sustained ≥1 hour]) that is uncomplicated and not associated with infection
•
Grade 3 neutropenia (ANC <1000/mm3) with maximal G-CSF use persisting for ≤ 7 days
•
Grade 4 neutropenia (ANC <500/mm3) with maximal G-CSF use persisting for ≤ 7 days
•
Grade 4 thrombocytopenia (<25,000/mm3) persisting for ≤ 7 days and not associated with 
grade 2 or greater bleeding
•
Grade 3 thrombocytopenia not associated with grade 2 or greater bleeding
•
Grade 3 anemia persisting for ≤ 7 days
3.1.2
Dose Escalation
Dose escalation of VIP152 and venetoclax with fixed doses of prednisone will proceed in cohorts 
of 3–6 participants at each dose level. The MTD is the dose level at which no more than 1 of up 
to 6 participants experience DLT during the DLT evaluation window(s), or the dose below that at 
which at least 2 (of ≤6) participants have DLT. If a participant did not experience a DLT and did 
not finish treatment during the DLT window, he or she will not be evaluable for toxicity and will 
be replaced in that dose level.
No new participants will initiate study treatment at the next higher (or lower) dose level until the 
required number of participants have completed DLT evaluation.  
Each dose-escalation or de-escalation decision will be documented in the study file. 
The report including the supporting safety data and delineation of each criteria met, with the dose-
escalation/de-escalation 
decisions 
will 
be 
provided 
to 
the 
Sponsor 
by 
email 
(OSROSafety@nih.gov) before additional participants will be enrolled onto the study. Sponsor 
approval will be required prior to continued enrolllment of participants on study. The Dose 
Escalation Determination form on the sponsor website: https://nih.sharepoint.com/:u:/r/sites/NCI-
CCR-OCD-Communications/SitePages/Forms-and-
Instructions.aspx?csf=1&web=1&e=uWBXtI  may be used for this purpose. 
Dose level 4 (VIP152 given at 30 mg IV weekly and Venetoclax 800 mg by mouth daily days 1-
10) is the RP2D based on a Phase 1 monotherapy studies in advanced cancers (lymphoma and 

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solid tumors) and is the maximum administered dose (MAD) in this study. If in dose level 4, 
DLTs occur in <33% of the participants, then the MTD will not be identified. In that case, the 
MAD of VIP152 at 30 mg IV and Venetoclax 800mg PO from dose level 4 will be used for further 
study as RP2D for this combination therapy.
NOTE: The dose of VIP152 and venetoclax selected for further evaluation may not be the MTD 
identified in the dose-escalation portion of the trial. The RP2D evaluated in the dose-expansion 
phase will be the dose or doses showing a maximal efficacy potential and minimal toxicity 
potential.
Table 1: VIP152 dose escalation
Dose Level
Dose of VIP152
Dose of Venetoclax
1
15 mg IV on day 2 and day 9
600 mg PO daily days 1-10
2
22.5 mg IV on day 2 and day 9
600 mg PO daily days 1-10
3
30 mg IV on day 2 and day 9
600 mg PO daily days 1-10
4
30 mg IV on day 2 and day 9
800 mg PO daily days 1-10
Table 2: Dose escalation rules
Number of Participants 
with DLT at a Given Dose 
Level
Escalation Decision Rule
0 out of 3
Enter up to 3 participants at the next dose level
> 2
Dose escalation will be stopped. This dose level will be declared the 
maximally administered dose (highest dose administered). Up to three
(3) additional participants will be entered at the next lowest dose level if
only 3 participants were treated previously at that dose.
1 out of 3
Enter up to 3 more participants at this dose level.
• If 0 of these 3 participants experience DLT, proceed to the next 
dose level.
• If 1 or more of this group experience DLT, then dose escalation is 
stopped, and this dose is declared the maximally administered dose. 
UP to three (3) additional participants will be entered at the next 
lowest dose level if only 3 participants were treated previously at 
that dose. 
<1 out of 6
This is the MTD and is generally the recommended Phase 2 dose. At 
least 6 participants must be entered at the recommended Phase 2 dose.
NOTE: If <1 out of 6 participants with DLT occurs at DL4, the MTD 
will not have been identified and DL4 will be declared the MAD for 
further study.
Participants will be monitored through all cycles of treatment for related toxicities. Dose-limiting 
toxicities are defined in Section 3.1.1 

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3.2
DRUG ADMINISTRATION
3.2.1
All Cycles
•
Venetoclax per specified dose level by mouth daily days 1-10a
•
VIP152 per specified dose level IV days 2 and 9
•
Prednisone 100mg by mouth daily days 1-10
•
Pegfilgrastim 6mg SQ on time dose on day 11b as supportive care
aVenetoclax tablets should be taken orally once daily with a meal and water. Do not chew, crush, 
or break tablets.
bPegfilgrastim may be self-administered by the participant.
Participants will be asked to complete and return a drug diary as a memory aid to help document 
the date and time of all self-administered study drugs. This drug diary as well as study drug 
containers and any unused study drug should be returned to the research team at the end of each 
cycle of therapy. Study drug accountability will be assessed per CCR SOP #PM-8 f.
3.2.2
Criteria for Starting a New Cycle of Study Therapy
A new course of study treatment may begin on Day 1 of a new cycle if:
•
ANC ≥ 1,000/μL and
•
Platelet count ≥ 50,000/μL and
•
No study drug-related ≥ Grade 3 toxicity 
If the criteria are not met, per investigator’s discretion, assessments may be repeated. The initiation 
of a new cycle of study therapy should be delayed until participant meets criteria to receive study 
drug as planned. 
3.2.3
Discontinuation of Treatment after CR
Participants who attain a CR following cycles 6 and/or 12 of study therapy will discontinue VVIP 
after completing 12 cycles of treatment. Participants who later experience disease 
relapse/progression >6 months following discontinuation of study therapy will be eligible for 
retreatment with VVIP if no additional cancer treatment was administered since the last dose of 
study therapy, the participant meets the safety parameters listed in the Inclusion/Exclusion criteria, 
and the trial is open. Participants will resume therapy at the same dose level and schedule that they 
were receiving at the time of initial treatment discontinuation and may receive up to a maximum 
of 12 additional cycles of study therapy (i.e., 24 cycles total). Participants who fail to achieve CR 
following cycles 6 and/or 12 of study therapy will continue VVIP therapy without interruption for 
up to a maximum of 24 total cycles of therapy.  
3.3
DOSE MODIFICATIONS
The following sections detail dose modifications guidelines for VIP152 and venetoclax based on 
documented toxicity. Dose modifications of prednisone will not be permitted. In general if 
overlapping toxicities occur with unclear attribution to study agent, dose reductions of venetoclax 
will be performed first with dose reductions of VIP152 performed second for recurrent toxicity.  
Recurrent toxicities or toxicities that are prolonged or severe may require dose modification of 
both study agents as applicable.

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3.3.1
Exceptions During DLT Evaluation Windows
In general, dose modifications should follow the schedule and guidelines below with the exception 
of the DLT evaluation window. Dose modifications of VIP152 and venetoclax should be avoided 
during the DLT evaluation window (i.e., Cycle 1) in order to allow identification of toxicities 
during the dose escalation phase (phase 1). A participant who experiences a DLT should be 
removed from protocol therapy (see Section 3.7.1) but will remain on study for all follow-up 
visits (safety, progression and survival).
In the case of an event otherwise meeting the DLT definition but occurring outside of the DLT 
window or any non-DLT that would require a dose modification, the offending drug(s) should be 
held for the remainder of the DLT evaluation window and consideration given to restarting it 
with dose modification in the next cycle.
3.3.2
Dose Modifications for VIP152
Every effort should be made to administer study intervention on the planned dose and schedule in 
the dose escalation cohort (phase 1). When clinically significant study intervention related 
toxicities are observed, appropriate and optimal treatment of the toxicity is assumed prior to 
considering dose modification as per Tables 4-7 below. For all treatment-emergent adverse events 
(TEAEs) the NCI CTCAE v5.0 will be used to assess the severity of TEAEs. 
The principles of the assessment of causal relationship between the adverse events and study drug 
are listed in Section 12.3 and 8.1.5.  If a participant experiences a TEAE that requires dose delay 
or modification, the next dose of VIP152 may be delayed for up to 21 days. If treatment is delayed 
for more than 21 days (except for hepatitis B reactivation), the participant should be withdrawn 
from study treatment. Dose will not be re-escalated to the original dose level after reduction for 
toxicity. Table 3 assumes 30 mg weekly IV is identified as the MTD/RP2D. If MTD/RP2D is 
identified as 22.5 mg, then the next lower dose (when “decrease 1 dose level” is called for) would 
be 15 mg. 
Table 3: Scheme for dose reduction of VIP152
Dose Reduction
Action
0
30 mg as a 30-minute IV infusion on day 2 and 9 of each cyclea
1
22.5 mg as a 30-minute IV infusion on day 2 and 9 of each cyclea
2
15.0 mg as a 30-minute IV infusion on day 2 and 9 of each cyclea
3
Discontinue study drug permanently
aThe dose will not be re-escalated after reduction for toxicity.  If more than 2 dose reductions are 
required, study drug will be discontinued permanently
Table 4: Platelet Criteria  for dose delay and dose modification
Grade
Platelets
(x109/L)
Dose Delay
Dose Modification
0 - 2
50
Treat on time
No change

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Grade
Platelets
(x109/L)
Dose Delay
Dose Modification
3 >7 days or 
with >G3 
bleeding
<50 – 25
Delaya until ≤ Grade 2 or 
baseline before treatment
Decrease 1 dose levelb
4
<25
Delaya until ≤ Grade 2 or 
baseline before treatment
Decrease 1 dose levelb
aIf no recovery to Grade ≤2 after 21 days delay, VIP152 treatment will be discontinued
bDose will not be re-escalated to original dose level after reduction for toxicity.  If more than 2 
dose reductions are required, treatment will be discontinued.
Table 5: ANC criteria for dose delay and dose modification
Grade
ANC
(x109/L)
G-CSF/ Dose delay
Dose modification
0 - 2
>1.0
No additional G-CSF required; 
Treat on time
No change
3 >7 days
<1.0 - 0.5
Consider additional G-CSF if 
neutropenia persists >3 days;
Delay VIP152a until Grade ≤2 
or baseline before treatment
No changeb
If the primary cause of neutropenia 
is thought to be lymphoma 
infiltration into the bone marrow, 
the investigator may elect not to 
reduce the dose of VIP152. 
Decisions must be made in 
consultation with and with approval 
of the Principal Investigator.
3
with fever 
≥38.5ºC and / 
or infection 
<1.0 -0.5
Consider additional G-CSF if 
neutropenia persists >3 days;
Delay VIP152a until Grade ≤2 
or baseline before treatment 
First occurrence:
No changeb
Second occurrence:
Decrease 1 dose level
Third occurrence:
Decrease 2 dose levelsc
If the primary cause of neutropenia 
is thought to be lymphoma 
infiltration into the bone marrow, 
the investigator may elect not to 
reduce the dose of VIP152. 
Decisions must be made in 
consultation with and with approval 
of the Principal Investigator.
4 >7 days
<0.5
Consider additional G-CSF if 
neutropenia persists >3 days;
Delay VIP152a until Grade ≤2 
or baseline before treatment
First occurrence: 
Decrease 1 dose level
Second occurrence: 

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Grade
ANC
(x109/L)
G-CSF/ Dose delay
Dose modification
If the primary cause of 
neutropenia is thought to be 
lymphoma infiltration into the 
bone marrow, the investigator 
may elect not to reduce the 
dose of VIP152. Decisions 
must be made in consultation 
with and with approval of the 
Principal Investigator.
Decrease 2 dose levelsc
ANC = absolute neutrophil count
aIf no ANC recovery to Grade ≤2 or baseline before treatment after 21 days dose delay: discontinue 
study treatment. 
bThe option to reduce 1 dose level may be discussed between the investigator and sponsor at any 
time. 
cDose will not be re-escalated to original dose level after reduction for toxicity.  If more than 2 
dose reductions are required, treatment will be discontinued.
Table 6: Hematological criteria (except for ANC and platelets) for dose delay and dose 
modification
Grade
Dose Delay
Dose Modification
0 - 2
Treat on time
No change
3 >7 days
Delaya until ≤ Grade 2 or baseline 
before treatment
Decrease 1 dose levelb
4
Delaya until ≤ Grade 2 or baseline 
before treatment
Decrease 1 dose levelb
aIf no recovery to Grade ≤2 after 21 days delay, VIP152 treatment will be discontinued
bDose will not be re-escalated to original dose level after reduction for toxicity.  If more than 2 
dose reductions are required, treatment will be discontinued.

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Table 7: Non-hematological criteria for dose delay and dose modification
Gradea
Dose delay
Dose modification
0 – 2
Treat on time
No change
3
Delayb until ≤ Grade 2
Decrease 1 dose levelc
4
Discontinue study drug permanently
Discontinue study drug permanently
aExcludes alopecia, non-refractory nausea / vomiting, and non-refractory diarrhea.
bIf no recovery to Grade ≤2 after 21 days delay, VIP152 treatment will be discontinued
cDose will not be re-escalated after reduction for toxicity.  If more than 2 dose reductions are 
required, treatment will be discontinued.
3.3.3
Dose modification for venetoclax
Every effort should be made to administer study intervention on the planned dose and schedule in 
the dose escalation cohort (phase 1). Sample guidelines for dose delay and/or modification of 
venetoclax are shown in Table 8. Venetoclax dose may be re-escalated (even to the full dose) if 
resolution of TEAEs occur following initial dose modification. See Table 9 for the dose levels for 
venetoclax dose reduction. Table 9 assumes 800 mg PO daily days 1-10 is identified as the 
MTD/RP2D. If MTD/RP2D is identified as 600 mg, then the next lower dose (when “decrease 1 
dose level” is called for) would be 400 mg.
A dose delay of 21 days is generally permitted for study therapy to allow recovery of hematologic 
toxicities to Grade  2 or non-hematologic toxicities to Grade  1. Actions for recurrent 
hematologic adverse events are described in Table 8. If treatment is delayed for more than 21 days 
(except for hepatitis B reactivation), the participant should be withdrawn from study treatment. 
Participants who discontinue all study treatment for adverse events should remain in the study and 
continue to have disease assessments through progression and standard follow-up.
Dose-modification guidelines should be evaluated and revised, as appropriate, based on the risk 
associated with the regimen employed.
Table 8: Guidelines for Dose Delay or Modification of Venetoclax
Event(s)
Dose Delay or Modification
Neutropenia: 
• Grade 3 (ANC <1,000/μL) 
for > 7 days, OR
• Grade 4 (ANC <500/μL) 
for any duration
•
Hold further doses of venetoclax.
•
Consider additional G-CSF if neutropenia persists >3 days.
-If ANC < 1000/L for < 7 days, administer full dose of study 
treatment for the next cycle.
-If ANC < 1000/L for > 7 days, reduce the dose of venetoclax 
by 1 dose level.
•
For subsequent episodes, further dose reduction of venetoclax 
and consideration of drug discontinuation will be considered.
•
If the primary cause of neutropenia is thought to be lymphoma 
infiltration into the bone marrow, the investigator may elect not 
to reduce the dose of venetoclax.  Decisions must be made in 
consultation with and with approval of the Principal 
Investigator.

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Event(s)
Dose Delay or Modification
Febrile neutropenia or 
neutropenia with infection
•
Hold further doses of venetoclax until resolution.
Thrombocytopenia: 
• Grade 3 (decrease to 
<50,000/ μL) associated 
with > Grade 2 bleeding, 
OR
• Grade 4 (decrease to 
<25,000/ μL) with or 
without bleeding
•
Hold further doses of venetoclax.
-If platelet count < 50,000/L for < 7 days, administer full dose 
of study treatment for the next cycle.
-If platelet count < 50,000/L for > 7 days, reduce the dose of 
venetoclax by 1 dose level.
•
For subsequent episodes, further dose reduction of venetoclax 
and consideration of drug discontinuation will be considered.
•
If the participant had baseline thrombocytopenia and the 
primary cause of thrombocytopenia is thought to be lymphoma 
infiltration into the bone marrow, the investigator may elect not 
to reduce the dose of venetoclax. Decisions must be made in 
consultation with and with approval of the Principal 
Investigator.
Grade 1 or 2 neutropenia 
and/or thrombocytopenia
•
No dose reduction or delay.
Any other Grade 4 toxicity 
or unmanageable Grade 3 
toxicity attributed to 
venetoclax
•
Hold further doses of venetoclax.
-If improves to < Grade 2 in < 7 days, administer full dose of 
study treatment for the next cycle.
-If improves to < Grade 2 in > 7 days, reduce the dose of 
venetoclax by 1 dose level.
•
For subsequent episodes, further dose reduction of venetoclax 
and consideration of drug discontinuation will be considered.
ANC = absolute neutrophil count; G-CSF = granulocyte colony-stimulating factor.
Table 9: Venetoclax Dose Reduction 
Dose Reduction
Venetoclax Dose
0
800 mg
1
600 mg 
2
400 mg 
3
200 mg 
4
Discontinue venetoclax
3.4
ON STUDY ASSESSMENTS/EVALUATIONS
The following describes all tests and procedures to be conducted on study and during treatment. 
Assessments will be performed according to the Study Calendar (Section 3.5). NOTE: Laboratory 
results from outside NIH are accepted unless otherwise requested or specified by the investigator 
due to safety concerns.

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3.4.1
Timing of Procedures
For each time period, consider the following order of assessments:
•
Screening: Refer to section 2.2
•
Baseline: Baseline assessments should be performed within 28 days of initiating treatment 
unless otherwise specified on the Study Calendar. Tests performed as part of screening do 
not need to be repeated if they were performed within the specified window prior to 
initiating treatment.
•
Study Drug Administration: See Section 3.2. Treatment will be given until confirmed 
progression, unacceptable toxicity (those TEAEs that require drug discontinuation as listed 
in the Dose Modification Section, Section 3.3 and in the DLT criteria, Section 3.1.1), or 
any criterion in Section 3.7.1 are met. Aggressive NHL participants who achieve CR 
following cycles 6 and/or 12 may discontinue therapy after completing 12 cycles (see 
Section 3.2.3). Dose administration may be delayed up to 21 days. If treatment is delayed 
for more than 21 days (except for hepatitis B reactivation), the participant should be 
withdrawn from study treatment. 
•
Treatment Cycles
o
Pre-Cycle Assessments: Assessments are to be performed on Day 1 of each cycle 
(-7 days for Cycle 1 and for all other cycles -3 days). If any baseline procedures are 
conducted within the timeframe necessary for Day 1 of Cycle 1 of trial treatment 
then the assessments scheduled on Cycle 1, Day 1 does not need to be repeated.
o
All Other On-Cycle Assessment Windows: A time window of ±1 day (except for 
Cycle 1 Day 2 PK testing). 
•
Disease Progression/ End of Treatment: When a participant who achieves CR completes 
all 12 cycles of treatment or for all other participants when meeting any of the other criteria 
listed in Section 3.7.1, all applicable activities of the Disease Progression/End of Treatment 
visit should be performed at the time of discontinuation ± 1 day. Any adverse events which 
are present at the time of discontinuation should be followed in accordance with the safety 
requirements outlined in Section 6.1. 
•
Unscheduled Visits: In the event of an unscheduled/unplanned visit (e.g., additional 
clinical assessment(s) due to toxicity), the investigator should use best clinical judgement 
as to the necessary assessments. In the event that the decision is made to continue treatment, 
all tests/assessments as required by the next visit on the Study Calendar (Section 3.5) 
should still be conducted (or repeated) within the applicable windows. If a decision is made 
to discontinue treatment, the participant should have a Disease Progression/End of 
Treatment Visit followed by post-therapy follow-up with tests/assessments completed (or 
repeated) within the applicable windows.
•
Safety Follow-up visit: The safety follow-up visit should occur 30 days (-2/+7 days) after 
the last dose of study drug.
•
Long-term Follow-up: All post-treatment visit(s) may be completed by remote visit (NIH 
approved remote platform used in compliance with local policy, including HRPP policy 
303) with a member of the study team (e.g., if the participant is not able to return to the 
NIH CC). Required labs/scans can be obtained by a local provider, with results sent in. A 

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participant may be referred to their local provider or asked to come to the NIH CC for an 
in-person assessment, if clinically indicated.
o
Prior to Disease Progression: Participants who discontinue trial treatment for a 
reason other than disease progression will move into the Follow-Up Phase and 
should be assessed as per the Study Calendar by clinical evaluation and radiologic 
imaging to monitor status. Every effort should be made to collect information 
regarding disease status until the start of new anti-neoplastic therapy, disease 
progression, death, or withdrawal/end of the study. All required testing is as noted 
in the Study Calendar. Follow-up will be every 3 months ±14 days for years 1, 
every 4 months ±14 days for year 2, every 6 months ±21 days for year 3, and every 
12 months  ±28 days for years 4 and 5. After 5 years of monitoring without disease 
progression the decision to continue further follow-up imaging, including any 
assessments and procedures, will be left to the discretion of the investigator. 
o
Survival/Post-Disease Progression: Once participant progress or start use of 
alternative antineoplastic therapy, they will be contacted approximately every 6 
months (± 28 days) from last dose by clinic visit or telephone to assess survival and 
the use of alternative antineoplastic therapy and stem cell transplant. Participants 
will be contacted until death, participant withdrawal, lost to follow-up, or study 
termination, whichever occurs first.
3.4.2
Description of Procedures
•
Medical history: a review of treatment history, any ongoing medical conditions and 
medical history pertaining to eligibility on study and involvement during study to 
determine eligibility as well as to assess safety.
•
Physical exam:  review of organ systems, height (at screening only), weight, and vital signs 
(i.e., temperature, pulse, respirations, blood pressure). After initiation of study drug, 
symptom-directed physical examinations will be performed. Exam conducted to determine 
eligibility, assess safety and assess efficacy of study regimen.
•
Performance status (ECOG):  an assessment of activities of daily living to determine 
eligibility and clinical benefit; see Appendix A
•
Laboratory assessments: The following comprises the required tests/analytes per panel.  
These may be performed outside NIH and results forwarded to the study team for review 
and management. Given that the methodologies utilized are similar across all laboratories, 
no significant variability is expected and there is no anticipation that study data will be 
affected.  
o
CBC with differential:  includes Neutrophils, Lymphocytes, Monocytes, 
Eosinophils, Basophils, WBC, RBC, Hemoglobin, Hematocrit, RBC Indices, 
MCV, RDW, Platelet. Performed to determine eligibility and to assess safety of 
regimen.
o
Acute care panel includes Sodium (NA), Potassium (K), Chloride (CL) Total CO2 
(Bicarbonate), Creatinine, Glucose, Urea nitrogen, eGFR. Performed to determine 
eligibility and to assess safety of regimen.

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o
Hepatic panel includes Alkaline Phosphatase, ALT/GPT, AST/GOT, Total 
Bilirubin, Direct Bilirubin. Performed to determine eligibility and to assess safety 
of regimen.
o
Mineral panel includes Albumin, Calcium, Magnesium, Phosphorus. Performed to 
assess safety of regimen.
o
LDH, uric acid, total protein – to assess safety of the regimen.
o
Urinalysis- to rule out infection and renal dysfunction at baseline.
o
24-hour urine creatinine – performed to determine eligibility if serum creatinine 
levels high. (Note: CrCl may also be calculated)
o
CMV serology and PCR – to establish eligibility and safety (reactivation)
o
EBV serology- for safety (reactivation) 
o
SARs CoV-2 PCR – to determine eligibility 
o
HIV, HBV and HCV testing – to determine eligibility and to monitor Hep B 
recurrence during the study in participants that screened positive
o
T-cell receptor gene arrangement, HTLV-1 serology (PTLC cohort only) – to 
determine eligibility 
o
IL-2R𝛼 (PTLC cohort only)- to determine efficacy
o
PT/INR, PTT – to determine eligibility 
o
Lymphocyte phenotype TBNK- to assess safety
o
Pregnancy test:  Urine or serum HCG - for individuals of child-bearing potential to 
determine eligibility, to determine pregnancy status prior to study drug 
administration and potential fetal drug exposure at safety visit
•
Optional tumor biopsy – correlative research studies (see section 5) 
•
Bone marrow aspiration and biopsy with flow cytometry – to assess disease status
•
EKG, ECHO – to determine eligibility 
•
CT scans- neck, chest, abdomen and pelvis; may be adjusted to assess additional known 
sites of disease, as needed, and/or MRI – to determine eligibility and assess disease status 
Scans during follow up may be performed at other sites. Given that the methodologies and 
machinery utilized are similar across all laboratories/providers, no significant variability is 
expected and there is no anticipation that study data will be affected.
•
Whole body 18F-FDG PET/CT or as clinically indicated – to determine eligibility and 
assess disease status
•
Adverse events and concomitant medication review:  Adverse events and concomitant 
medication will be continuously monitored throughout the study until disease progression 
or end of treatment visit. Adverse events that occur beyond 30 days after the last 
administration will be recorded per Section 6.1. 
•
Correlative studies: Refer to section 5
3.4.3
Additional Information
3.4.3.1
Pregnancy Testing
Individuals of childbearing potential (ICBP) must have a pregnancy test prior to day 1 of each 
cycle.

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3.4.3.2
Response Assessments
Tumor response will be assessed by the investigator using the Lugano Classification Response 
Criteria for NHL (Appendix D).
NOTE: For participants who continue on  active treatment, refer to the Study Calendar for the 
imaging to be done as well as for other assessments and testing required at the time of each 
response assessment, including applicable pre-cycle windows. If a participant stops treatment 
for any reason other than disease progression, response assessments should still be performed at 
the similar time frames noted. If restaging imaging is performed per the above schedule and a 
participant’s treatment is then delayed for toxicity, repeat imaging does not need to be performed 
again prior to the new day 1 of the delayed treatment cycle.
3.4.3.3
Suspected CR
If the investigator suspects CR based on clinical, radiographic and/or laboratory evaluation 
during treatment, the following procedures are also required to confirm CR:
In NHL participants: 
•
Imaging by CT or MRI; and PET if applicable (i.e., clinically indicated)
•
Bone marrow aspirate and biopsy with flow cytometry (only if biopsy at screening was 
positive)
3.4.3.4
Disease Progression
At the time of suspected or confirmed disease progression either during or following treatment as 
part of post-treatment follow-up prior to first disease progression, the following are required:
•
Imaging by CT or MRI; and PET if applicable (i.e., clinically indicated)
•
Soluble IL-2R𝛼 (PTCL cohort)
•
Bone marrow aspirate and biopsy with flow cytometry if applicable (i.e., clinically 
indicated)
The following assessments should also be performed:
•
Symptom-guided clinical assessment with physical exam
•
T/B/NK cell count
•
Research blood samples (see Section 5)
•
Optional tumor biopsy (if accessible)
NOTE: In the event that disease progression is not confirmed, yet a decision is made to initiate a 
new anti-cancer treatment for any reason, all of these assessments should be done prior to start 
of the new therapy.

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3.5
STUDY CALENDAR 
3.5.1
Screening, Baseline, and Treatment
Treatment Cycle
Procedure
Cycle 1
Cycle 2
Cycles 3+ 
Study Cycle/Day/Time point:
(1 cycle = 21 days)
Screening1
Baseline2
1
2
3
9
15
1
2
9
15
1
2
9
15
Scheduling Window (Days)
-28/+0
-7
0
0
±1
±1
-3
0
±1
±1
-3
0
±1
±1
Venetoclax
D1-10
D1-10
D1-10
Prednisone
D1-10
D1-10
D1-10
VIP152
X
X
X
X
X
X
Tissue/Pathologic Review3
X
Medical History
X
Physical Exam and ECOG PS
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
X
X
X
X
X
X
EKG
X
ECHO
X
Bone Marrow Aspiration/Biopsy4
X
X (post-C6 & C12)
Symptoms/Adverse Events
X
X
X .............................................................................X
Concomitant Medications
X
X
X .............................................................................X
CBC/differential
X
X
X
X
X
X
X
X
X
X
X
Acute Care and Mineral Panels
X
X
X
X
X
X
X
X
X
X
X
X
X
Hepatic Panel
X
X
X
X
X
X
X
X
X
X
X
LDH and Uric acid
X
X
X
X
X
X
X
X
X
X
X
X
X
Total protein
X
X
X
X
24-hour urine for CrCl if needed per 2.2.2.2
X
HIV, Hepatitis B, and Hepatitis C screening 
(Antibody / Antigen)
X
Hepatitis B PCR testing 
(if initial screen positive)
X
prior to each treatment cycle in participants positive for Hepatitis B  (See Section 4.1.7)

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Treatment Cycle
Procedure
Cycle 1
Cycle 2
Cycles 3+ 
Study Cycle/Day/Time point:
(1 cycle = 21 days)
Screening1
Baseline2
1
2
3
9
15
1
2
9
15
1
2
9
15
Scheduling Window (Days)
-28/+0
-7
0
0
±1
±1
-3
0
±1
±1
-3
0
±1
±1
Coagulation Panel (PT/INR, PTT)
X
T/B/NK Cell Subsets
X
X
X
X
Soluble IL-2R𝛼 (PTCL only)
X
X
X
X
Urinalysis
X
X
EBV PCR
X
X
X
X
CMV PCR
X
X
X
X
HTLV-I serology and TCR rearrangement (PTCL 
only)
X
SARs-CoV-2
X
Pregnancy Test
X
X
X
X
X
Radiologic Imaging (CT/MRI)5
X
X
X (pre-
odd 
cycles)
PET Imaging6
X
X (pre-
C7 & 
C13)
Study Drug Diary7
X
X
X
Biomarker Blood Samples
X
X
X (Day 11)
X
X
Optional Tumor Tissue/Biopsy8
X
PG Samples/Germline DNA
X
PK Samples9
X
X
X
X 
(C4)
NOTE: Additional assessments may be done as clinically indicated.

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1 Screening evaluations should be performed within 28 days, with the following exceptions: Confirmation of diagnosis (no time limit); HIV, Hepatitis B 
and Hepatitis C testing (within 3 months).
2 Any Screening/Baseline tests performed within the specified time frame for Cycle 1 Day 1 treatment do not need to be repeated.
3 Archival tumor tissue will be accessed/reviewed at Screening for confirmation of diagnosis and eligibility (no time limit applies to this review; i.e., may be 
>28 days).
4 Repeat bone marrow aspiration and biopsy with flow cytometry in follow-up following C6 and C12 if required to confirm suspected CR (if positive at 
baseline); otherwise, repeat only if clinically indicated.
5 CT neck, chest, abdomen and pelvis preferred (with IV and PO contrast unless contraindicated); MRI may be used if modality preferred to assess disease. The 
same imaging performed at Screening should be performed in follow-up to assess for response, or as clinically indicated; CT neck may be omitted after the 
baseline scan in participants without neck disease. See Section 2.2.2.3 for additional information. In addition, in case of suspected CR or PD at or between 
regular visits, see required testing in Sections 3.4.3.3 and 3.4.3.4 , respectively. NOTE: The window for pre-cycle imaging assessments is 28 days prior to 
cycle 1 and 7 days prior to the start of subsequent cycles.
6 Repeat PET Imaging (i.e., whole body 18F-FDG PET/CT or as clinically indicated) to confirm suspected CR (if positive at baseline) following C6 and 
C12 and at end-of-treatment; otherwise, repeat only if clinically indicated.
7 Participants will be given a Study Drug Diary with each cycle to document administration of oral study drugs. 
8 Archival tissue will be accessed for research correlates, if available. Participants may also have an optional fresh tumor biopsy at baseline and at disease 
progression/recurrence if accessible tumor and acceptable risk. See Section 5. If a fresh biopsy was taken at screening, then an additional biopsy will not 
be taken at baseline.
9 Only select participants will undergo PK testing to ensure a large enough sample size for adequate analysis. Plasma samples collected on C1D2 will be 
drawn pre-dose and 30 min (+/-15 min), 45 min (+/-15 min), 1- (+/-15 min), 2- (+/-15 min), 4- (+/-15 min), 6- (+/-15 min), 8- (+/-15 min), and 24-hours 
(+/-15 min) post-study drug dosing. Plasma samples collected on C2D2 and C4D2 will be drawn 30 min (+/-15 min), 45 min (+/-15 min), 2- (+/-15 
min), and 4- (+/-15 min) hours post-study drug dosing. See Section 5.1 

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3.5.2
End of Treatment and Post-Treatment Follow-Up
Post-Treatment Follow-Up
Procedure
Safety
Follow-Up (Pre-
PD) 1st year post 
EOT
Follow-Up (Pre-
PD) 2nd year post 
EOT
Follow-Up (Pre-
PD) 3rd  year post 
EOT
Follow-Up (Pre-
PD) 4-5th  year 
post EOT
Survival (Post-
PD)
Study Cycle/Day/Time point:
(1 cycle = 21 days)
Disease 
Progression/ End of 
Treatment
30 days
Q 3 months
Q 4 months
Q 6 months
Q 12 months
Q6months
Scheduling Window (Days)
±1 day
-2/+7 days
±14 days
±14 days
±21 days
±21 days
±28 days
Medical History
X
Physical Exam and ECOG PS
X
X
X
X
X
X
Vital Signs
X
X
X
X
X
Bone Marrow 
Aspiration/Biopsy1
X
Symptoms/Adverse Events
X
X
Concomitant Medications
X
X
X
X
X
X
CBC/differential
X
X
X
X
X
X
Acute Care and Mineral Panels
X
X
X
X
X
X
Hepatic Panel
X
X
X
X
X
X
LDH and Uric acid
X
X
X
X
X
X
Total protein
X
X
X
X
X
X
Hepatitis B PCR testing (if 
initial screen positive)
with each scheduled follow-up visit through 12 
months after EoT in participants positive for 
Hepatitis B  (See Section 4.1.7)
T/B/NK Cell Subsets
X
X
X
X
X
X
Soluble IL-2R𝛼 (PTCL only)
X
X
X
X
X
X
Urinalysis
X
EBV PCR
X
X
X
X
X
X
CMV PCR
X
X
X
X
X
X
Pregnancy Test
X
Radiologic Imaging (CT/MRI)
X
X
X
X
X
PET Imaging2
X
Biomarker Blood Samples3
X
X
X
X
X
Optional Tumor Tissue/Biopsy
X (at disease progression/recurrence)

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Post-Treatment Follow-Up
Procedure
Safety
Follow-Up (Pre-
PD) 1st year post 
EOT
Follow-Up (Pre-
PD) 2nd year post 
EOT
Follow-Up (Pre-
PD) 3rd  year post 
EOT
Follow-Up (Pre-
PD) 4-5th  year 
post EOT
Survival (Post-
PD)
Study Cycle/Day/Time point:
(1 cycle = 21 days)
Disease 
Progression/ End of 
Treatment
30 days
Q 3 months
Q 4 months
Q 6 months
Q 12 months
Q6months
Scheduling Window (Days)
±1 day
-2/+7 days
±14 days
±14 days
±21 days
±21 days
±28 days
Survival Status4
X
1 Repeat bone marrow aspiration and biopsy with flow cytometry in follow-up following C6 and C12 if required to confirm suspected CR (if positive 
at baseline); otherwise, repeat only if clinically indicated. 
2 Repeat PET Imaging (i.e., whole body 18F-FDG PET/CT or as clinically indicated) to confirm suspected CR (if positive at baseline) following C6 and 
C12 and at end-of-treatment; otherwise, repeat only if clinically indicated.
3.Correlative blood samples (e.g., Streck, red top, and CPT tubes) will be collected at each follow-up visit (pre-PD) and at disease progression/recurrence. 
See Section 5.
4 After 5 years of follow-up without disease progression, or upon progression or initiation of alternative antineoplastic therapy, participants will be 
contacted approximately every 6 months (±28 days) from last dose of study drug(s) by clinic visit or telephone to assess survival, including collection of 
information regarding additional treatment(s)/interventions. Participants will be contacted until death, participant withdrawal, lost to follow-up, or study 
termination, whichever occurs first. NOTE: Investigators should continue to report serious adverse events that are attributed to the study treatment in 
follow-up.

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3.6
COST AND COMPENSATION
3.6.1
Costs
NIH does not bill health insurance companies or participants for any research or related clinical 
care that participants receive at the NIH Clinical Center.  If some tests and procedures performed 
outside the NIH Clinical Center, participants may have to pay for these costs if they are not covered 
by their insurance company.  Medicines that are not part of the study treatment will not generally 
be provided or paid for by the NIH Clinical Center
3.6.2
Compensation 
Participants will not be compensated on this study 
3.6.3
Reimbursement
The NCI will cover the costs of some expenses associated with protocol participation.  Some of 
these costs may be paid directly by the NIH and some may be reimbursed to the 
participant/guardian as appropriate.  The amount and form of these payments are determined by 
the NCI Travel and Lodging Reimbursement Policy.
3.7
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA
Every effort must be made to have all participants complete a safety visit approximately 30 (-2/+7) 
days following the last dose of study therapy.
3.7.1
Criteria for removal from protocol therapy
Participants who meet the following criteria should be discontinued from protocol therapy:
•
Completion of 12 cycles of protocol therapy in those achieving CR (see Section 3.2.3)
•
Completion of 24 cycles of protocol therapy (see Section 3.2.3)
•
Disease progression
•
Intercurrent illness that prevents further administration of treatment
•
Delay of treatment for more than 21 days (except for hepatitis B reactivation), unless it 
is felt by the Principal Investigator to be in the participant’s best interests to remain on 
study.
•
Unacceptable adverse event(s) (see Sections 3.1.1 and 3.3), unless it is felt by the 
Principal Investigator to be in the participant’s best interests to remain on study (e.g., 
discontinue offending study agents while continuing others).
•
Participant withdrawal of consent at any time
•
Noncompliance with trial treatment or procedure requirements in the opinion of the 
investigator; such a decision/rationale will be clearly noted in the medical record
•
Participant requires a prohibited concomitant medication
•
Pregnancy
•
Investigator’s decision to withdraw the participant
•
Study is cancelled for any reason

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All participants, regardless of reason for discontinuation of study treatment (with the exception of 
withdrawal of consent; unless consent to follow-up activities is documented) will be followed for 
progression and survival.
3.7.2
Off-Study Criteria
Participants who meet the following criteria should be discontinued from the study:
•
Completed study follow-up period
•
Screen failure and/or failure to maintain eligibility (i.e., between enrollment and day 1 
of drug) where changes in eligibility parameters are not felt to be study-intervention 
related (e.g., TLS prophylaxis) and initiation of treatment is not felt to be in the best 
interests of the participant in the opinion of the investigator (Section 2.4)
•
Participant requests to be withdrawn from study
•
Participant is lost to follow-up
•
Death
•
Study is cancelled for any reason
3.7.3
Lost to Follow-up
A participant will be considered lost to follow-up if he or she fails to return for two (2) scheduled 
visits and is unable to be contacted by the study site staff. 
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit:
•
The site will attempt to contact the participant and reschedule the missed visit within 5 
business days and counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain if the participant wishes to and/or should continue in the study.
•
Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, an IRB approved certified letter to the participant’s last known mailing address 
or local equivalent methods). These contact attempts should be documented in the 
participant’s medical record or study file. 
•
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.
4
CONCOMITANT MEDICATIONS/MEASURES
All concomitant medications (including start / stop dates, total daily dose, and indication) taken 28 
days before the first dose and while on study must be recorded in the participant’s source 
documentation as well as in the appropriate pages of the case report form (CRF).  This includes 
also antiemetic therapy and contrast media, which might be administered during assessment of 
tumor lesions. All concomitant medications should be reported to the investigator. 
In general, participants should be closely monitored for side effects of all concomitant medications 
regardless of elimination pathway, especially those with narrow therapeutic indices, such as 
warfarin, phenytoin, quinidine, carbamazepine, phenobarbital, cyclosporine, and digoxin.

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4.1
PERMITTED THERAPY
4.1.1
Growth Factors
Participants will be monitored for the development of treatment-emergent neutropenia per 
protocol-specified laboratory testing. Growth factor support is allowed and should follow 
institutional guidelines and the protocol schedule for the administration of pegfilgrastim. 
Additional supplementation of long-acting G-CSF (e.g., pegfilgrastim) with short-acting G-CSF 
(e.g., filgrastim) is permitted for severe or prolonged neutropenia and should be considered for 
grade 3 of 4 neutropenia that persists for >3 days despite receipt of pegfilgrastim.
4.1.2
Prophylaxis of Pneumocystis Jiroveci (Previously Pneumocystis Carinii)
Adult participants should receive prophylaxis for Pneumocystis Jiroveci during study therapy 
administration. Trimethoprim/sulfamethoxazole 1 DS tablet by mouth on Monday, Wednesday, 
and Friday is the preferred schedule.
Participants allergic to either component may receive inhaled pentamidine 300 mg once a month 
or other standard treatments.
Treatment will begin with initiation of study therapy and will be stopped upon completion of study 
therapy unless continued administration beyond this point is deemed necessary based on 
inadequate immune reconstitution.
4.1.3
Tumor Lysis Syndrome
TLS is a risk for participants with lymphoid malignancies who are treated with high cell-killing 
agents, including venetoclax. Participant will be monitored closely for laboratory evidence of 
tumor lysis syndrome (TLS) prior to and during treatment with venetoclax. Perform tumor burden 
assessment with CT scan and CBC with WBC differential, assess blood chemistry (potassium, 
uric acid, phosphorus, calcium, and creatinine) in all participant and correct pre-existing 
chemistry abnormalities prior to initiation of treatment with venetoclax. Elective admission for 
fluid hydration, correction of electrolyte abnormalities and closer monitoring is permitted and 
will not be considered an SAE.
Participant who show laboratory evidence of TLS as determined by elevated uric acid with 
hyperkalemia, hyperphosphatemia and/or elevated creatinine will be admitted to the hospital for 
appropriate management with intravenous fluids. Participant will receive prophylaxis as outlined 
in the guidelines below prior to the first cycle with venetoclax; this can be discontinued during 
subsequent cycles if there is no clinical or laboratory evidence of TLS as deemed by the 
investigator. Participant who develop electrolyte changes suggestive of TLS should undergo 
aggressive management and further monitoring per Appendix C
Guidelines:
TLS is a risk for participant with lymphoid malignancies who are treated with high cell-killing 
agents, including venetoclax. Changes in blood chemistries consistent with TLS that require 
prompt management can occur as early as 6 to 8 hours following the first dose of venetoclax. The 
risk of TLS is a continuum based on multiple factors, including tumor burden and comorbidities. 
Risk is highest for those with bulky disease, elevated leukocyte count, elevated pre-treatment 
LDH levels, compromised renal function, and dehydration. Perform tumor burden assessment 
with CT scan and CBC with WBC differential, assess blood chemistry (potassium, uric acid, 

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phosphorus, calcium, and creatinine) in all participant and correct pre-existing chemistry 
abnormalities prior to initiation of treatment with venetoclax.
All participants should receive prophylaxis for TLS before the initiation of the first dose of 
venetoclax. Prophylaxis will include the following:
•
Appropriate hydration, consisting of a fluid intake of approximately 2 3 L/day starting 24-
48 hours before the start of treatment
•
Administration of an agent to reduce uric acid (standard prophylaxis will involve 
Allopurinol 600 mg at least 24 hours prior to venetoclax with 300 mg daily for a minimum 
of the first 10 days of therapy) or rasburicase IV (given at least 24 hours prior to venetoclax 
for those high-risk participant with elevated uric acid levels before treatment, or when 
otherwise judged to be appropriate by the investigator) until normalization of serum uric 
acid and other laboratory evidence of TLS (e.g., elevated serum LDH levels).
•
Laboratory results should be reviewed, and electrolyte values should not demonstrate any 
clinically significant abnormalities before the first dose of venetoclax, or the participant 
should receive additional prophylactic treatment and hydration before the initiation of 
dosing.
Guidelines for Hospitalization Due to TLS Risk:
Participant exhibiting specific characteristics at screening or initiation of venetoclax treatment are 
considered to be at high risk of developing TLS and should be hospitalized for more intensive 
prophylaxis and monitoring for the initial dose of venetoclax. These participants are identified by 
the presence of any of the following:
•
Any lymph mass  10 cm on the screening CT scan
•
Absolute lymphocyte count (ALC) > 25 x 109/L AND any lymph mass > 5cm
In addition to high-risk characteristics above, other participant characteristics may suggest an 
increased risk of TLS. These include, but are not limited to, the following:
•
Overall disease burden (e.g., several enlarged lymph nodes, even if none reaching 10 cm)
•
Elevated LDH levels
•
Compromised renal function, as evidenced by low creatinine clearance < 80 mL/min
•
Extensive bone marrow involvement
•
Dehydration or concern about inability to meet oral hydration requirements (i.e., 
approximately 2-3 L/day 24-48 hours prior to and during study therapy)
Hospitalization is not mandatory for participant exhibiting these characteristics, but these and any 
other factors considered relevant to TLS should be considered in an overall assessment of the 
participant’s state and their risk of TLS. Investigators should use their judgment in assessing TLS 
risk for their participant and may optionally hospitalize any participant they consider to be at risk 
for TLS for closer monitoring; elective admission will not be considered an SAE.

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Hospitalization Procedures:
For participants requiring hospitalization, hospitalization will begin 1 day prior to the first dose of 
venetoclax and continue for a minimum of 24 hours after receiving initial venetoclax dosing. Upon 
admission, serum chemistry and hematology laboratory samples should be drawn and IV hydration 
should be started with a target of 150200 cc/hr or as clinically appropriate. Laboratory results 
should be reviewed, and electrolyte values should not demonstrate clinically significant 
abnormalities before the first dose of venetoclax; otherwise, the participant should receive 
additional prophylactic treatment and hydration before the initiation of dosing. A nephrology (or 
acute dialysis) service should be consulted/contacted on hospital admission (per institutional 
standards) to ensure emergency dialysis is available and the appropriate staff is aware and prepared 
to handle any necessary intervention for TLS. Telemetry should also be considered.
High-risk participants who are hospitalized for TLS monitoring will have serial vital signs and 
TLS laboratory samples drawn (acute care panel, mineral panel, LDH, uric acid, and CBC with 
differential) prior to venetoclax dosing as well as 4 hours (+/- 60 min.), 8 hours (+/- 60 min.), 12 
hours (+/- 60 min.), and 24 hours (+/- 60 min.) post-dose.  Laboratory values obtained before the 
dose of venetoclax are to be used to determine whether a participant developed a change related 
to TLS.  Laboratory results of the 24-hour post-dose should be reviewed before receiving the dose 
of venetoclax for that day.  Participant who develop electrolyte changes suggestive of TLS should 
undergo aggressive management and further monitoring per Appendix C.
4.1.4
Standard Medical Care
Standard medical care for oncology will be provided for all other issues including treatment of 
neutropenic fever, transfusions of blood and platelets for cytopenias as well as pain, nausea, 
diarrhea management, etc. Furthermore, participants may receive palliative and supportive care 
for any underlying illness.  
4.1.5
Hormone-Replacement Therapy
Participant who use oral contraceptives, hormone-replacement therapy, or other maintenance 
therapy should continue their use.
4.1.6
Corticosteroids
Short courses of corticosteroids (< 7 days) for non-cancer-related medical reasons (e.g., treatment 
for rash, arthritis, asthma) or for the prevention or treatment of study drug related side effects (e.g., 
tumor flare, rash, etc.) at doses that do not exceed 100 mg per day of prednisone or equivalent are 
permitted.
Participant may receive a brief ( 7 days) course of systemic steroids ( 100 mg/day prednisone 
or equivalent) prior to initiation of study therapy for control of lymphoma-related symptoms.
The use of topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal 
systemic absorption) is also permitted.
4.1.7
Monitoring and Treatment for Hepatitis B Reactivation
Participants who test positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody 
(HBcAb) and not acutely infected are at varying risk for reactivation of Hepatitis B. Participants 
may be included in the study provided that they have an undetectable HBV DNA level prior to 
starting therapy. 

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These participants should be treated with entecavir (or equivalent) during study treatment and for 
at least 12 months after completion of study treatment to prevent hepatitis B reactivation. These 
participants should also have HBV DNA levels obtained with each treatment cycle and at each 
scheduled follow-up visit in surveillance for at least 12 months after the last cycle of therapy by 
means of real‑time PCR with the use of an assay that has a sensitivity of at least 10 IU/mL. 
If the HBV DNA assay becomes positive and is < 100 IU/mL, the participant should be retested 
within 1-2 weeks. If the assay is still positive, study treatment must be held, and the participant 
should be immediately referred to a gastroenterologist or hepatologist for management.  
If a participant’s HBV DNA level exceeds 100 IU/mL while receiving antiviral medication, study 
treatment must be permanently discontinued.
4.1.8
Palliative Radiotherapy
Palliative radiotherapy during the study will be allowed for local pain control provided that:
•
In the opinion of the investigator, the participant does not have progressive disease
•
No more than 10% of the participant’s bone marrow is irradiated and
•
The radiation field does not encompass a target lesion; radiation to a target lesion is 
considered progressive disease and the participant should come off study
The safety of VIP152 administered concomitantly to radiation therapy has not been determined.  
Therefore, VIP152 treatment should be paused during palliative radiotherapy.  Discussion with the 
sponsor is recommended before restarting treatment.
4.1.9
Non-conventional therapies
Treatment with “non-conventional therapies” (such as acupuncture), and vitamin / mineral 
supplements are permitted if they do not interfere with the study endpoints, in the opinion of the 
investigator.  They must be recorded in the source notes and the CRF.
4.1.10 Other Anti-infective Prophylaxis
Antiviral, antifungal and antibacterial prophylaxis for participants at risk of infections per 
institutional guidelines are permitted as long as strong inducers or inhibitors of CYP3A are not 
used (See Appendix B). 
4.2
CONCOMITANT MEDICATIONS TO BE USED WITH CAUTION
Concomitant medications that fall into the categories below could potentially lead to adverse 
reactions and should be considered cautionary (except where noted).  If a potential study 
participant is taking any of the medications in the categories described below, the investigator must 
assess and document the use of medications known or suspected to fall in the following medication 
categories:
•
Moderate/weak CYP3A inducers such as efavirenz and oxcarbazepine
•
CYP2C8 substrates such as thiazolidinediones (glitazones) and select statins (because of 
expected inhibition of the metabolism of CYP2C8 substrates by venetoclax)
•
CYP2C9 substrates such as tolbutamide (because of expected inhibition of the metabolism 
of CYP2C9 substrates by venetoclax).  It is recommended to exclude CYP2C9 substrates 
with a narrow therapeutic index such as phenytoin.

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•
P-gp inhibitors such as ketoconazole, ritonavir, posaconazole, and rifampin and P-gp 
substrates such as digoxin
4.2.1
CYP3A Inhibitors/Inducers
Venetoclax is metabolized primarily by CYP3A. Avoid co-administration with moderate CYP3A 
inhibitors and consider alternative agents with less CYP3A inhibition. 
If the benefit outweighs the risk and a moderate CYP3A inhibitor must be used, monitor participant 
for toxicity and follow dose modification guidance as needed (Section 3.3). If a moderate CYP3A 
inhibitor or P-gp inhibitor is used, the dose of venetoclax should be reduced by 50%. The 
venetoclax dose used prior to concomitant use of the moderate CYP3A inhibitor or P-gp inhibitor 
may be resumed 2-3 days after discontinuation of the inhibitor. Participants should avoid grapefruit 
and Seville oranges during treatment, as these contain moderate inhibitors of CYP3A. 
Co-administration of venetoclax with strong CYP3A inducers, such as rifampin, is prohibited on 
study. Avoid concomitant use of strong CYP3A inducers (e.g., carbamazepine, rifampin, 
phenytoin, and St. John’s Wort) and consider alternative agents with less CYP3A induction.
Use of moderate CYP3A inducers or inhibitors is prohibited in the phase 1 dose-escalation portion 
of the study to allow for accurate assessment of DLTs and determination of MTD. 
A list of common CYP3A inhibitors or inducers is provided in Appendix B; a comprehensive list 
of inhibitors, inducers, and substrates may be found at: 
http://medicine.iupui.edu/clinpharm/ddis/table.aspx.
This website is continually revised and should be checked frequently for updates. 
4.2.2
Antifungal Agents
Given the overlapping toxicity of these targeted agents as well as other immunosuppressive 
therapies, such as steroids, there is an increased risk of infectious complications, including 
potential invasive fungal infections.  Participant on this study will be undergoing frequent imaging 
for response evaluation and the investigators will also evaluate these imaging studies for potential 
infectious complications, including possible invasive fungal infection.  Further work-up may 
include, but is not limited to, peripheral blood analysis for fungal blood markers and/or 
bronchoscopy with BAL testing for fungal markers/cultures and other infectious pathogens.  
Antifungal therapy with echinocandins, such as micafungin or caspofungin, as well as treatment 
with ambisome are permitted on study if deemed clinically appropriate. Due to the strong 
inhibition of CYP3A with certain azoles (e.g., voriconazole, posaconazole, itraconazole or 
ketoconazole), treatment with any of these agents is prohibited while receiving venetoclax therapy.  
Azole treatment during the days the participant is not receiving study therapy is permitted as long 
as enough time is permitted for the azole therapy to be out of the participant’s system prior to 
initiation of the next cycle of study therapy that includes venetoclax. Furthermore, azoles with less 
CYP3A inhibition such as isavuconazole may be considered with close monitoring for toxicity and 
consideration of dose reduction of study medications. Consultation with the infectious disease 
team as well as pharmacy is recommended to help guide antifungal use in participant being treated 
on study. Prophylactic antifungals will not be routinely used given the low estimated risk of fungal 
infections with cyclic, non-continuous dosing of targeted agents and prednisone and significant 
potential for drug-drug interactions with these antifungal agents.

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4.2.3
QT Prolongation
Any medications known to cause QT prolongation should be used with caution; periodic ECG and 
electrolyte monitoring should be considered. 
4.3
PROHIBITED THERAPY
Participant who require the use of any of the excluded therapies listed below will be discontinued 
from study treatment.  
Use of the following therapies is prohibited during the study:
•
Other investigational treatment or other anticancer therapy (e.g., chemotherapy) while on 
this protocol
•
Immunotherapy
•
Hormone therapy (other than contraceptives, hormone replacement therapy, or megestrol 
acetate)
The following concomitant medications are not allowed from 14 days or 5 half-lives of the drug 
(whichever is shorter) prior to the first dose of study drugs and during study drug administration:
•
Strong CYP3A4 inhibitors
•
Strong CYP3A4 inducers
•
Moderate CYP3A inhibitors (dose-escalation cohort only)
•
Moderate CYP3A inducers (dose-escalation cohort only)
See Appendix B for a list  of medications  that fall into these categories.
4.3.1
Vaccines
Live-virus vaccines should not be given within 28 days prior to the initiation of study treatment or 
at any time during study treatment.
4.3.1.1
Clarification regarding vaccination against COVID-19: 
Vaccines currently authorized or approved for use against COVID-19 in the United States include 
mRNA vaccines (Pfizer and Moderna vaccines) and a viral vector vaccine (JNJ-78436735 
manufactured by Janssen Pharmaceuticals). 
In general, it is preferred that participants considering vaccination or booster against COVID-19 
complete the vaccination procedures prior to enrollment. However, if the subject chooses to 
receive a COVID-19 vaccination or booster after enrollment, a discussion will be had with the 
Sponsor Medical Monitor to agree upon a safe and appropriate vaccination strategy in terms of 
timing and safety. 
For participants in the study, vaccination against COVID-19 with a vaccine authorized or 
approved in the United States is permitted. Relevant details regarding vaccination will be 
documented as a concomitant medication and will include the name of the manufacturer of the 
COVID-19 vaccine. Any adverse events thought to be related to the vaccine will be recorded in 
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5
CORRELATIVE STUDIES FOR RESEARCH
5.1
BIOSPECIMEN COLLECTION
Samples will be collected for exploratory objectives to evaluate biomarkers of sensitivity or 
resistance to study therapy. In blood, circulating tumor DNA (ctDNA) response and correlation 
with molecular tumor analysis is planned in addition to the other analyses described below. In 
tumor, analyses may include gene expression profiling for DLBCL cell-of-origin and molecular 
profiling for DLBCL genetic subtype. Molecular characterizations may identify altered signalling 
patterns or mutations that associate with response or resistance to study treatment.
Sample
Collection Details*
Time Points
Storage and 
Processing 
Laboratory/ 
Laboratory 
for 
Analysis^
Blood Samples
ctDNA/cfDNA, 
Plasma banking
2 x 10 mL Streck/BCT tube
Cytokines, Serum 
banking
(exploratory- 
response and 
ctDNA)
1 x 8-10 mL SST
(or red top tube)
Peripheral blood 
mononuclear cells 
(PBMCs)
1
x 8 mL Cell 
Preparation Tubes 
(CPTs)
(with sodium citrate)
• Baseline/Pre-Cycle 1
• Cycle 1 Day 11
•  Day 1 , pre-dose of each 
subsequent cycle
•  Follow-up visits (Pre-PD)
• Disease Progression/End-of-
Treatment
BPC/
Staudt/
Adaptive
Pharmacokinetic 
(PK) Studies
1 x 6 mL NaHep tube
1 x 2 mL EDTA
(purple top tube)
• C1D2: pre-VIP152 dose and 30 
min (+/-15 min), 45 min (+/-15 
min), 1- (+/-15 min), 2- (+/-15 
min), 4- (+/-15 min), 6- (+/-15 
min, 8- (+/-15 min), and 24-hours 
(+/-15 min) post-dose
• C2D2: 30 min (+/-15 min), 45 
min (+/-15 min), 2- (+/-15 min), 
and 4- (+/-15 min) hours post-
VIP152 dose
• C4D2: 30 min (+/-15 min), 45 
min (+/-15 min), 2- (+/-15 min), 
and 4- (+/-15 min) hours post-
VIP152 dose
Pharmacogenetic 
(PG) Studies
1 x 10 mL EDTA
(purple top tube)
• Baseline/Pre-Cycle 1
BPC/
Vincerx

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Sample
Collection Details*
Time Points
Storage and 
Processing 
Laboratory/ 
Laboratory 
for 
Analysis^
Tissue Samples
Archival and/or 
Fresh Tissue Biopsy
FFPE (block or slides)
Excision (single or multiple 
nodes) or core (4-6 passes); 
placed in formalin/FFPE and 
media, frozen, as appropriate
• Archival tissue will be accessed, if 
available
• Baseline* (optional)
• Disease progression/ recurrence 
(optional)
NCI LP/Staudt
Other Samples
Germline DNA 
(exploratory – 
molecular correlates 
of response)
Blood, Buccal Swab, or 
Saliva (preferred)
• Baseline/Pre-Cycle 1 preferred
BPC/Staudt
*Only to be offered if a fresh biopsy sample was not taken at screening
^ The location of specimen processing or analysis may be adjusted with the permission of the PI or laboratory
investigator.
NOTE:
• Tubes/media may be adjusted at the time of collection based upon materials available. As written above, all 
blood/ tubes, aside from PK and PG samples, should remain at ambient temperature after collection and until 
processing. PK and PG samples should be placed on wet ice and refrigerated until processing. Processing 
windows: Streck tubes are generally stable for at least 7 days until processing; SST/red top tubes, Na Hep, 
EDTA, and CPT tubes should be processed same day, whenever possible.
• Portions of all samples may be banked for future research analyses; prospective consent will be obtained 
during the informed consent process.
5.2
SAMPLE COLLECTION, PROCESSING AND ANALYSES
Note: Platforms and procedures for analysis may be adjusted based upon current technology and/or 
collaborations in place at the time of actual analyses.
5.2.1
Tissue Samples
5.2.1.1
Archival tissue
•
Archival block(s) or slides (e.g., 15 unstained slides, 5-microns) will be collected, when 
available from prior or future routine procedures.
5.2.1.2
Lymph node excision or core needle biopsy procedure
•
Participant with accessible tumor tissue who agree to have an optional biopsy performed 
will be as outlined in the table in Section 5.1. These samples will be processed as per the 
standard operating procedures of the Hematopathology Section of the Laboratory of 
Pathology, NCI, including fresh frozen (FF), formalin-fixed, paraffin-embedded (FFPE) 
tissue, and/or viably frozen single-cell suspension.
•
Optional tumor biopsies will be obtained by core needle biopsy or surgery. If core biopsies 
are collected, it is preferable that the interventional radiologist will collect 4-6 core needle 
biopsies. Biopsies for research will be performed only if there is minimal risk of morbidity. 

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Deep-seated organs such as lung will be excluded from biopsy for research purposes. 
General anesthesia will not be performed to obtain biopsies for research purposes but 
when necessary, conscious sedation may be used. If a biopsy is being performed for 
medical or diagnostic purposes, with or without general anesthesia, a sample may be 
obtained for research purposes, if adequate tissue is available to meet medical or 
diagnostic purposes, upon participant consent.
•
NOTE: Image-guidance with ultrasound or other non-ionizing radiation methods may be 
used for tissue acquisition; image-guidance with ionizing radiation techniques (e.g., CT 
guidance) may be performed for optional biopsy at baseline and time of progressive 
disease.
•
Studies to be performed on these samples include: Whole-exome sequencing, low-pass 
whole-genome sequencing, RNA-sequencing and copy-number analysis for determination 
of molecular and genetic subtype of DLBCL as well as correlation of molecular features 
of disease to response or resistance to study therapy.
5.2.2
Blood Samples
5.2.2.1
Cell-free DNA (cfDNA)/Circulating Tumor DNA (ctDNA) and plasma banking
•
Disposition of samples: send to BPC and refer to section 5.3.3 for more details on sample 
tracking and storage.
•
Upon arrival in the BPC, samples will be centrifuged, and the plasma transferred into 
cryovials for storage at -80ºC until the time of analysis. 
•
Samples will be processed and stored by BPC until time of analysis.
•
Samples will be processed and stored at BPC. Samples will then be sent to Adaptive 
Biotechnologies where all analyses will be performed. Analyses to be performed on these 
samples at Adaptive Biotechnologies include: Circulating tumor DNA (ctDNA) for 
amplification and sequencing of the VDJ segment of the immunoglobulin receptor as well 
as immunosequencing studies of the T-cell receptor repertoire. Purpose of ctDNA 
collection is for dynamic monitoring of treatment response during therapy and for active 
surveillance of disease recurrence during follow-up. Adaptive Biotechnologies will use a 
proprietary method (i.e., ClonoSEQ) for amplifying and analyzing immunoglobulin 
receptor sequences, allowing unprecedented sensitivity and specificity. 
•
Data from experiments conducted by Adaptive Biotechnologies using the human material 
will be provided to NCI and such data provided by Adaptive Biotechnologies to NCI may 
be used by NCI for any purpose. Only coded samples will be shared for sample storage and 
tracking. The samples and data will be sent to Adaptive Biotechnologies at the address 
listed below:
Adaptive Biotechnologies Corp.
1551 Eastlake Ave E
Suite 200
Seattle WA 98102
5.2.2.2
Cytokines, ctDNA and serum banking
•
Disposition of samples: send to BPC and refer to section 5.3.3 for more details on sample 
tracking and storage.

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•
Upon arrival in the BPC, samples will be centrifuged, and the serum transferred into 
cryovials for storage at -80ºC until the time of analysis. 
•
Samples will be processed and stored by BPC until time of analysis.
•
Samples will be processed and stored at BPC. Samples will then be sent to a collaborating 
lab that has yet to be determined for analyses and will be updated in a future protocol 
amendment, if required. 
•
Studies to be performed on these samples include: Cytokine analysis (e.g., IL-6, IL-10, 
interferon beta, TNF alpha, mutational analysis and storage of peripheral blood.
5.2.2.3
Pharmacokinetic Studies
NOTE:  Select participants will undergo pharmacokinetic (PK) testing at timepoint outlined in the 
table in Section 5.1.  Participant selection for PK testing will depend on ensuring an adequate 
number of participants with full data points within each dose level to provide a complete PK 
analysis across all dose levels.  The decision as to which participants will undergo such testing 
will be left to the discretion of the investigator. 
NOTE: Timing of PK sample collection: Every effort will be made to collect samples for PK 
analysis as prescribed in the protocol above. If the timing is not strictly adhered to, it will not be 
considered a Protocol Deviation. 
NaHep tube Processing:
•
Put samples immediately on wet ice and refrigerate
•
The date and exact time of each blood draw should be recorded on the sample tube and the 
PK sheet. 
•
Disposition of samples: send to BPC and refer to section 5.3.3 for more details on sample 
tracking and storage.
•
Upon arrival in the BPC, samples will be centrifuged, and the plasma transferred into 
cryovials for storage at -80ºC until the time of analysis. 
•
Samples will be processed, stored, and analyzed by BPC.  
•
Analyses to be performed by BPC: Bioanalytical measurements of venetoclax and 
prednisone will be conducted on an ultra HPLC-MSMS system using validated assays for 
each drug developed and validated by the Clinical Pharmacology Program. The measured 
exposure for each drug assayed will be used to correlate to pharmacodynamic (PD) 
endpoints, clinical response, toxicity, and pharmacogenetic (PG) analyses.  VIP152 plasma 
concentrations will be assessed by a validated LC/MS/MS assay by Vincerx.
EDTA tube Processing:
•
Draw blood into the 2 mL K3EDTA Lavender Top Tube labeled PK (indicating appropriate 
PK timepoint) 
•
After filling the tubes, gently invert the tubes eight (8) to ten (10) times. 
•
Immediately after blood sampling, use aluminum foil to wrap the blood collection tubes to 
keep them light protected. 
•
Store blood sample until centrifugation in a refrigerator or in an iced water bath.  When 
using an ice bath, cover with an opaque box or store it as long as possible in a dark 
environment (eg. in a cabinet).  The tubes must not be exposed to daylight or neon light for 
more than 30 minutes and never to direct sunlight. 

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•
Centrifuge blood sample at approximately 2000g approximately 10 minutes preferably in 
a pre-cooled centrifuge at approximately 4°C. 
•
Immediately after centrifugation, using disposable plastic transfer pipette, transfer the 
plasma as two aliquots into two separate brown polypropylene tubes both labeled as “PK 
Plasma ” with appropriate timepoint indicated.  
•
Each tube must contain at least 0.4 ml of plasma.
•
Discard the Lavender top tube 2mL in an appropriate medical waste container. 
•
Store the sample promptly and in an upright position at ≤ -20°C in a temperature-controlled 
freezer until shipment to QPS. 
•
Samples to be shipped FROZEN to QPS at the address listed below:
Attn: Sample Coordination QPS, LLC
3 Innovation Way, Suite 240
Newark, DE 19711
Tel: 302-369-5120
Email: GBASCG@qps.com
•
Analyses to be performed by BPC: Bioanalytical measurements of venetoclax and 
prednisone will be conducted on an ultra HPLC-MSMS system using validated assays for 
each drug developed and validated by the Clinical Pharmacology Program. The measured 
exposure for each drug assayed will be used to correlate to pharmacodynamic (PD) 
endpoints, clinical response, toxicity, and pharmacogenetic (PG) analyses.  VIP152 plasma 
concentrations will be assessed by a validated LC/MS/MS assay by Vincerx.
5.2.2.4
Pharmacogenetic Studies
•
Put samples immediately on wet ice and refrigerate. 
•
Disposition of samples: send to BPC and refer to section 5.3.3 for more details on sample 
tracking and storage.
•
Upon arrival in the BPC, samples will be centrifuged, and the plasma transferred into 
cryovials for storage at -80ºC until the time of analysis.
•
Samples will be processed, stored, and analyzed by BPC.  
•
One blood sample per participant will be collected in a purple top tube (K2EDTA; BD 
Biosciences) for pharmacogenetic studies to analyze the genomic DNA and assess 
genotype of the most relevant drug metabolizing enzymes and transporters (DMET) in the 
Clinical Pharmacology Program. 
•
Analyses to be performed by BPC: DNA will be analyzed on a Pharmacoscan 
(ThermoFisher Scientific) genotyping platform that tests for 4,627 genetic variations in 
1,191 drug disposition genes, including cytochrome P450s (CYPs), Glutathione 
transferases (GSTs), sulfotransferases (SULTs), as well as genes involved in facilitation of 
drug transporters, global regulation of drug metabolizing/transporting proteins, drug 
binding proteins, and drug targets.
5.2.2.5
Peripheral Blood Mononuclear Cells (PBMCs)
• Collect blood in Cell Preparation Tubes (e.g., red and green speckled top); gently invert 
the tubes 8-10 times immediately after collection and place on a shaker if not processed 
immediately.  

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•
Disposition of samples: send to BPC and refer to section 5.3.3 for more details on sample 
tracking and storage.
•
PBMCs will be isolated per routine laboratory techniques by the BPC.  Samples will be 
sent to a collaborating lab that has yet to be determined for analyses and will be updated in 
a future protocol amendment, if required.  
•
Studies to be performed on these samples: isolation of PBMCs for RNA sequencing and 
microRNA sequencing in order to assess for the expression of genes in peripheral blood 
that correlate with clinical outcomes and disease progression.
5.2.3
Other Samples
•
Germline DNA will be collected by blood, buccal swab, and/or saliva samples (preferred).  
•
These will ideally be collected at baseline; however, may be collected at any point on study 
based on supplies.  
•
Standardized, commercial collection kits or tubes will be used (e.g., 1 x 5-10 mL K2EDTA 
tube for blood; Isohelix SK-1 for buccal swabs; Salviette/Oragene® for saliva).  In the case 
of buccal swabs, two (2) samples may be collected in order to ensure adequate DNA 
collection.
•
The samples will be processed and DNA extracted/isolated per kit instructions and 
established techniques.  These will also be handled by the BPC (see Section 5.3.3 for 
contact information).  
•
For possible planned analyses, see Section 5.4.
5.3
SAMPLE STORAGE, TRACKING AND DISPOSITION
5.3.1
General
All specimens obtained in the protocol are used as defined in the protocol. Any specimens that are 
remaining at the completion of the protocol will be stored in the conditions described below.  The 
study will remain open so long as sample or data analysis continues.  Samples from consenting 
participants will be stored until they are no longer of scientific value or if a participant withdraws 
consent for their continued use, at which time they will be destroyed.  
Samples will be ordered in CRIS and tracked through a Clinical Trial Data Management system.  
Should a CRIS screen not be available, the CRIS downtime procedures will be followed.  Samples 
will not be sent outside NIH without appropriate approvals and/or agreements. The PI will record 
any loss or unanticipated destruction of samples as a deviation. Reporting will be per the 
requirements of section 7.2.
5.3.2
Hematopathology Section of Laboratory of Pathology (Tissue samples)
Archival and/or freshly collected and processed tumor tissue may be stored in the 
Hematopathology Section of Laboratory of Pathology until ready for planned and/or future 
research assays if the participant has agreed to allowing specimens to be used in future research 
studies.  IRB approval will be obtained before using any samples to conduct studies that are not 
described within this protocol.  Samples will be stored under conditions appropriate to the type of 
sample and processing (e.g., ambient or frozen).  
Tissue that is given to the technician will be assigned an accession number (HP#) in the HP Case 
Logbook; sample tracking also takes place with a FileMaker Pro data base called HP Participant 
Information and Specimen Inventory.   A participant background sheet may be filled out and filed 

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with any accompanying paperwork, with final reports and any supplemental reports that follow 
added as completed.
5.3.3
Blood Processing Core/Clinical Pharmacology Program
Please e-mail NCIBloodcore@mail.nih.gov at least 24 hours before transporting samples (the 
Friday before is preferred).
For sample pickup, page 102-11964.
For immediate help, call 240-760-6180 (main blood processing core number) or, if no answer, 
240-760-6190 (main clinical pharmacology lab number).
For questions regarding sample processing, contact NCIBloodcore@mail.nih.gov
The samples will be processed, barcoded, and stored in the lab until requested by the investigator.
5.3.3.1
Sample Data Collection
All samples sent to the Blood Processing Core (BPC) will be barcoded, with data entered and 
stored in Labmatrix utilized by the BPC. This is a secure program, with access to Labmatrix limited 
to defined  BPC personnel, who are issued individual user accounts. Installation of Labmatrix is 
limited to computers specified by the BPC. These computers all have a password restricted login 
screen. 
Labmatrix creates a unique barcode ID for every sample and sample box, which cannot be traced 
back to participants without Labmatrix access. Data will be recorded for each sample as 
appropriate (e.g. the participant ID, name, trial name/protocol number, time drawn, cycle time 
point, dose, material type, as well as box and freezer location). Participant demographics 
associated with the clinical center patient number are provided in the system. For each sample, 
there are notes associated with the processing method (delay in sample processing, storage 
conditions on the ward, etc.).
5.3.3.2
Sample Storage and Destruction
Barcoded samples are stored in barcoded boxes in a locked freezer at either -20 or -80C according 
to stability requirements.  
Access to stored clinical samples is restricted. Samples will be stored until requested by a 
researcher named on the protocol. All requests are monitored and tracked in Labmatrix. All 
researchers are required to sign a form stating that the samples are only to be used for research 
purposes associated with this trial (as per the IRB approved protocol) and that any unused samples 
must be returned to the BPC. It is the responsibility of the NCI Principal Investigator to ensure that 
the samples requested are being used in a manner consistent with IRB approval.
Following completion of this study, samples will remain in storage as detailed above. Access to 
these samples will only be granted following IRB approval of an additional protocol, granting the 
rights to use the material. 
If, at any time, a participant withdraws from the study and does not wish for their existing samples 
to be utilized, the individual must provide a written request. Following receipt of this request, the 
samples will be destroyed (or returned to the participant, if so requested). The PI will record any 
loss or unanticipated destruction of samples as a deviation. Reporting will be per the requirements 
of Section 7.

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Sample barcodes are linked to participant demographics and limited clinical information. This 
information will only be provided to investigators listed on this protocol, via registered use of the 
Labmatrix. It is critical that the sample remains linked to participant information such as race, age, 
dates of diagnosis and death, and histological information about the tumor, in order to correlate 
genotype with these variables.
5.3.4
Staudt Lab
5.3.4.1
Sample Data Collection
Participant samples, collected for research under this IRB approved protocol, may be archived in 
the Staudt laboratory. All data associated with archived clinical research samples is entered into 
the web-based NCI Labmatrix database, a centralized system with access controlled via centralized 
login. Access to this database for samples collected from this study is limited to Dr. Staudt and his 
research staff, each requiring individual login and password. All staff in the laboratory receive 
annually updated NIH/CITI or other training, as appropriate, and maintain standards of computer 
security. 
The data recorded for each sample may include the participant ID, trial name/protocol number, 
date drawn/collected, treatment cycle/time point, sample source (e.g., peripheral blood, marrow, 
tissue, etc.) as well as box and freezer location. All received samples will be given a unique bar 
code number, which will be added to the sample NCI Labmatrix database. Only this bar code will 
be recorded on the sample vial and the vials will not be traceable back to Participants without 
authorized access to the NCI Labmatrix database.
5.3.4.2
Sample Storage
Samples are stored in freezers at -80°C (e.g., sera, plasma, tissue samples) or under liquid nitrogen 
(e.g., cells), according to established stability requirements. These freezers are located onsite under 
the direction of Dr. Staudt. Access to samples from this protocol for research purposes will be as 
outlined in this protocol or by permission of the Principal Investigator only. 
5.3.5
Study Completion, Future Use and Sample Destruction
The study will remain open so long as sample or data analysis continues. Following completion of 
the planned analyses, samples will remain in storage as detailed above. Tissue specimens and 
derived tissue lysates, RNA and DNA collected in the course of this research project may be 
banked and used in the future to investigate new scientific questions related to this study that are 
not expressly stated in the present protocol. However, this research may only be done if proposed 
research has undergone prospective IRB review and approval, including consent/reconsent if 
required.
If the participant withdraws consent the participant’s data will be excluded from future 
distributions, but data that have already been distributed for approved research use will not be able 
to be retrieved. 
The PI will record any loss or unanticipated destruction of samples as a deviation. Reporting will 
be per the requirements of section 7.2

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5.4
SAMPLES FOR GENETIC/GENOMIC ANALYSIS
5.4.1
Description of the scope of genetic/genomic analysis
The research correlates for this Phase 1/2 study are expected to include DNA/RNA sequencing of 
tumors, including circulating tumor (ct) DNA, and PBMCs as well as sequencing of germline DNA 
as a comparison. In addition, whole exome sequencing may include evaluation for known 
lymphoma mutations. For any genetic studies are performed, the results will be deposited in a 
database such as dbGaP per NIH requirements. Although there is controlled access to such a 
database, such a submission carries theoretical risks of revealing the identity of the participant. 
This is discussed in the consent.
5.4.2
Description of how privacy and confidentiality of medical information/biological 
specimens will be maximized
Confidentiality for genetic samples will be maintained as described (Section 5.3). In addition, 
a Certificate of Confidentiality has been obtained for this study.
5.4.3
Management of Results
Participants will be contacted if a clinically actionable gene variant is discovered. Clinically 
actionable findings for this study are defined as disorders appearing in the American College 
of Medical Genetics and Genomics recommendations for the return of incidental findings that 
is current at the time of primary analysis. 
Participants will be contacted at this time with a request to provide a blood sample to be sent to 
a CLIA certified laboratory. If the research findings are verified in the CLIA certified lab, the 
participant will be offered the opportunity to come to NIH (at our expense) to have genetic 
education and counseling to explain this result. If the participant does not want to come to NIH, a 
referral to a local genetic healthcare provider will be provided (at their expense).
This is the only time during the course of the study that incidental findings will be returned. No 
interrogations regarding clinically actionable findings will be made after the primary analysis.
6
DATA COLLECTION AND EVALUATION
6.1
DATA COLLECTION
The PI will be responsible for overseeing entry of data into a 21 CFR Part 11-compliant data 
capture system provided by the NCI CCR and ensuring data accuracy, consistency, and timeliness. 
The principal investigator, associate investigators/research nurses and/or a contracted data 
manager will assist with the data management efforts. Primary and final analyzed data will have 
identifiers so that research data can be attributed to an individual human participant.
All adverse events (AEs), including clinically significant abnormal findings on laboratory 
evaluations, regardless of severity, will be followed until return to baseline or stabilization of 
event.
Document AEs from the date of first dose of any study drug, through 30 days after the last dose of 
any study drug. Beyond 30 days after the last intervention, only adverse events which are serious 
and related to the study intervention need to be recorded.

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End of study procedures: Data will be stored according to HHS, FDA regulations, and NIH 
Intramural Records Retention Schedule as applicable.
6.1.1
Data Collection/Recording Exceptions
6.1.1.1
Abnormal Laboratory Values
An abnormal laboratory value will be considered an AE if the laboratory abnormality is 
characterized by any of the following:
•
Results in discontinuation from the study
•
Is associated with clinical signs or symptoms 
•
Requires treatment or any other therapeutic intervention
•
Is associated with death or another serious adverse event, including hospitalization
•
Is judged by the Investigator to be of significant clinical impact
•
If any abnormal laboratory result is considered clinically significant, the investigator will 
provide details about the action taken with respect to the test drug and about the 
participant’s outcome.
The PI (or designee) evaluation of each AE not captured in the clinical database determining that 
it meets the criteria above will be documented in the source documents. If any abnormal laboratory 
result is considered clinically significant, the investigator will provide details about the action 
taken with respect to the test drug and about the participant’s outcome. Note: the investigator 
performing the assessment must be a licensed physician listed on the 1572.
6.2
DATA SHARING PLANS
6.2.1
Human Data Sharing Plan
What data will be shared?
I will share human data generated in this research for future research as follows:
 X  Coded, linked data in an NIH-funded or approved public repository.  
 X  Coded, linked data in BTRIS (automatic for activities in the Clinical Center)
 X Coded, linked or identified data with approved outside collaborators under appropriate 
agreements.
How and where will the data be shared? 
Data will be shared through:
 X  An NIH-funded or approved public repository.  Insert name or names: ClinicalTrials.gov, 
dbGaP.
 X  BTRIS (automatic for activities in the Clinical Center)
 X  Publication and/or public presentations.
When will the data be shared?
 X  At the time of publication or shortly thereafter.
6.2.2
Genomic Data Sharing Plan
Unlinked genomic data will be deposited in public genomic databases such as dbGaP in 
compliance with the NIH Genomic Data Sharing Policy.

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6.3
RESPONSE CRITERIA
Overall response assessments will include evaluation of physical examinations, recording of 
symptoms, hematological evaluations, and radiographic evaluations as per the schedule of 
assessments (see Study Calendar Section 3.5). Participants will be restaged during treatment and 
post-treatment until year 5, or until progression. If no progression after 5 years of monitoring, the 
decision to continue further follow-up imaging and assessments will be left to the discretion of the 
investigator. Response assessments will be performed according to the Lugano Classification 
Response Criteria in NHL (Appendix D), as assessed by investigators. 
NOTE: PET/CT hybrid scanners may be used to acquire the required CT images only if the CT 
produced by the scanner is of diagnostic quality, adheres to the specified slice thickness/scan 
parameters, and includes the use of intravenous (IV) contrast.
If using a hybrid machine to acquire both PET and CT, the PET must be performed prior to the 
CT with IV contrast as to not compromise PET results.
If independent CT and PET scanners are used, and the participant is receiving both scans on the 
same day, the PET must be performed prior to the CT with IV contrast.
6.3.1
Definitions
Best overall response: The best overall response is the best response recorded from the start of the 
treatment until disease progression/recurrence (taking as reference for progressive disease the 
smallest measurements recorded since the treatment started). The participant’s best response 
assignment will depend on the achievement of both measurement and confirmation criteria.
Time to response: The time to response is  response is defined as the time from the start of the 
treatment until time of first objective response.
6.3.2
Duration of Response
Duration of overall response: The duration of overall response is measured from the time 
measurement criteria are met for CR or PR (whichever is first recorded) until the first date that 
recurrent or progressive disease is objectively documented (taking as reference for progressive 
disease the smallest measurements recorded since the treatment started).
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that progressive disease is objectively documented.
Duration of stable disease: Stable disease is measured from the start of the treatment until the 
criteria for progression are met, taking as reference the smallest measurements recorded since the 
treatment started, including the baseline measurements.
6.3.3
Event-Free Survival
Event-free survival (EFS) is defined as the duration of time from the date of study enrollment until 
time of disease relapse, disease progression, alternative therapy given (such as radiation), or death, 
whichever occurs first.  
6.3.4
Progression-Free Survival
Progression-free survival (PFS) is defined as the duration of time from the date of study enrollment 
until time of disease relapse, disease progression, or death, whichever occurs first.

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6.3.5
Overall Survival
Overall survival (OS) is defined as the duration of time from the date of study enrollment until 
death.
6.4
TOXICITY CRITERIA
The following adverse event management guidelines are intended to ensure the safety of each 
participant while on the study. The descriptions and grading scales found in the revised NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE 
reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 
5.0. A copy of the CTCAE version 5.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm).
7
NIH REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING 
PLAN
7.1
DEFINITIONS
Please refer to definitions provided in Policy 801: Reporting Research Events found at: 
https://irbo.nih.gov/hrpp-policy-guidelines/.
7.2
OHSRP OFFICE OF COMPLIANCE AND TRAINING / IRB REPORTING
7.2.1
Expedited Reporting
Please refer to the reporting requirements in Policy 801: Reporting Research Events and Policy 
802 Non-Compliance Human Subjects Research found at: https://irbo.nih.gov/hrpp-policy-
guidelines/. Note: Only IND Safety Reports that meet the definition of an unanticipated problem 
or present new information that might affect the willingness of participants to enroll or remain 
on the study will need to be reported per these policies.
7.2.2
IRB Requirements for PI Reporting at Continuing Review
Please refer to the reporting requirements in Policy 801: Reporting Research Events found at: 
https://irbo.nih.gov/hrpp-policy-guidelines/.
7.3
NCI CLINICAL DIRECTOR REPORTING
Problems expeditiously reviewed by the OHSRP in the NIH eIRB system will also be reported 
to the NCI Clinical Director/designee; therefore, a separate submission is not necessary.
In addition to those reports, all deaths that occur within 30 days after receiving a research 
intervention should be reported via email unless they are due to progressive disease.
To report these deaths, please send an email describing the circumstances of the death to 
NCICCRQA@mail.nih.gov within one business day of learning of the death.
7.4
NIH REQUIRED DATA AND SAFETY MONITORING PLAN
7.4.1
Principal Investigator/Research Team
The clinical research team will meet on a regular basis (approximately weekly) when 
participants are being actively treated on the trial to discuss each participant. Decisions about 
dose level enrollment and dose escalation if applicable will be made based on the toxicity data 
from prior participants.

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All data will be collected in a timely manner and reviewed by the principal investigator or a lead 
associate investigator. Events meeting requirements for expedited reporting as described in section 
7.2.1 will be submitted within the appropriate timelines.
The principal investigator will review adverse event and response data on each participant to 
ensure safety and data accuracy. The principal investigator will personally conduct or supervise 
the investigation and provide appropriate delegation of responsibilities to other members of the 
research staff.
8
SPONSOR SAFETY REPORTING
8.1
DEFINITIONS
8.1.1
Adverse Event
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product (ICH E6 (R2))
8.1.2
Serious Adverse Event (SAE)
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following:
•
Death,
•
A life-threatening adverse event (see 8.1.3)
•
Inpatient hospitalization or prolongation of existing hospitalization
o
A hospitalization/admission that is pre-planned (i.e., elective or scheduled surgery 
arranged prior to the start of the study), a planned hospitalization for pre-existing 
condition, or a procedure required by the protocol, without a serious deterioration in 
health, is not considered a serious adverse event.
o
A hospitalization/admission that is solely driven by non-medical reasons (e.g., 
hospitalization for patient or subject convenience) is not considered a serious adverse 
event.
o
Emergency room visits or stays in observation units that do not result in admission to 
the hospital would not be considered a serious adverse event. The reason for seeking 
medical care should be evaluated for meeting one of the other serious criteria.
•
Persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions
•
A congenital anomaly/birth defect.
•
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition.

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8.1.3
Life-threatening
An adverse event or suspected adverse reaction is considered "life-threatening" if, in the view of 
either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an adverse event or suspected adverse reaction that, had it occurred in a 
more severe form, might have caused death. (21CFR312.32)
8.1.4
Severity
The severity of each Adverse Event will be assessed utilizing the CTCAE version 5.0.
8.1.5
Relationship to Study Product
All AEs will have their relationship to study product assessed using the terms: related or not 
related.
•
Related – There is a reasonable possibility that the study product caused the adverse event. 
Reasonable possibility means that there is evidence to suggest a causal relationship 
between the study product and the adverse event.
•
Not Related – There is not a reasonable possibility that the administration of the study 
product caused the event.
8.2
ASSESSMENT OF SAFETY EVENTS
AE information collected will include event description, date of onset, assessment of severity and 
relationship to study product and alternate etiology (if not related to study product), date of 
resolution of the event (return to baseline or stabilization), seriousness, and outcome. The 
assessment of severity and relationship to the study product will be done only by those with the 
training and authority to make a diagnosis and listed on the Form FDA 1572 as the site principal 
investigator or sub -investigator. AEs occurring during the collection and reporting period will be 
documented appropriately regardless of relationship. AEs will be followed through resolution 
(return to baseline or stabilization).
SAEs will be:
•
Assessed for severity and relationship to study product and alternate etiology (if not related 
to study product) by a licensed study physician listed on the Form FDA 1572 as the site 
principal investigator or sub-investigator.
•
Recorded on the appropriate SAE report form, the medical record and captured in the 
clinical database.
•
Followed through resolution by a licensed study physician listed on the Form FDA 1572 
as the site principal investigator or sub-investigator.
For timeframe of recording adverse events, please refer to section 6.1. 
8.3
REPORTING OF SERIOUS ADVERSE EVENTS
All serious adverse events recorded from the time of first investigational product administration 
through 30 days after the last dose of any study drug must be reported to the sponsor with the 
exception of any listed in section 8.4. Beyond 30 days after the last dose of any study drug, only 
serious adverse events which are related to study drug are to be recorded and must be reported to 
the sponsor. Any AE that meets protocol-defined serious criteria or meets the definition of Adverse 

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Event of Special Interest that require expedited reporting must be submitted immediately (within 
24 hours of awareness) to OSRO Safety using the CCR SAE report form. Any exceptions to the 
expedited reporting requirements are found in section 8.4.
All SAE reporting must include the elements described in section 8.2. SAE reports will be 
submitted via an electronic SAE reporting system (e.g., HiLIT). In the event of system downtime 
or issues, SAE reports will be submitted using the CCR SAE Report form to the sponsor at:
OSROSafety@mail.nih.gov. CCR SAE report form
and instructions can be found at: https://nih.sharepoint.com/:u:/r/sites/NCI-CCR-OCD-
Communications/SitePages/Forms-and-Instructions.aspx?csf=1&web=1&e=uWBXtI 
Following the assessment of the SAE by OSRO, other supporting documentation of the event may 
be requested by the OSRO Safety and should be provided as soon as possible.
8.4
WAIVER OF EXPEDITED REPORTING TO CCR
As death due to disease progression is part of the study objectives (PFS), and captured as an 
endpoint in this study, they will not be reported in expedited manner to the sponsor. However, if 
there is evidence suggesting a causal relationship between the study drug and the event, report 
the event in an expedited manner according to section 8.3.
8.5
SAFETY REPORTING CRITERIA TO THE PHARMACEUTICAL COLLABORATORS
Reporting will be per the collaborative agreement, see Section 11. 
8.6
REPORTING PREGNANCY
All 
required 
pregnancy 
reports/follow-up 
to 
OSRO 
will 
be 
submitted 
to: 
OSROSafety@mail.nih.gov. 
 
Forms 
and 
instructions 
can 
be 
found 
here: 
https://nih.sharepoint.com/:u:/r/sites/NCI-CCR-OCD-Communications/SitePages/Forms-and-
Instructions.aspx?csf=1&web=1&e=uWBXtI 
8.6.1
Maternal exposure
If a participant becomes pregnant during the course of the study, the study treatment should be 
discontinued immediately, and the pregnancy reported to the Sponsor no later than 24 hours of 
when the Investigator becomes aware of it. The Investigator should notify the Sponsor no later 
than 24 hours of when the outcome of the Pregnancy become known,
Pregnancy itself is not regarded as an SAE. However, congenital abnormalities or birth defects 
and spontaneous miscarriages that meet serious criteria (section 8.1.2) should be reported as SAEs.
The outcome of all pregnancies should be followed up and documented until 90 days after the last 
dose study drug. 
8.6.2
Paternal exposure
Male participants should refrain from fathering a child or donating sperm during the study and for 
90 days after study drug.
Pregnancy of the participant’s partner is not considered to be an AE. However, the outcome of 
all pregnancies  occurring from the date of the first dose until 90 days after the last dose of study 
drug in female partners of male participants should be followed up and documented.  Pregnant 
partners may be offered the opportunity to participate in an institutional pregnancy registry 

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protocol (e.g., the NIH IRP pregnancy registry study) to provide data about the outcome of the 
pregnancy for safety reporting purposes.
8.7
REGULATORY REPORTING FOR STUDIES CONDUCTED UNDER CCR-SPONSORED IND
Following notification from the investigator, CCR, the IND sponsor, will report any suspected 
adverse reaction that is both serious and unexpected in expedited manner to the FDA in accordance 
to 21 CFR 31.2.32.  CCR will report an AE as a suspected adverse reaction only if there is evidence 
to suggest a causal relationship between the study product and the adverse event.  CCR will notify 
FDA and all participating investigators (i.e., all investigators to whom the sponsor is providing 
drug under its INDs or under any investigator’s IND) in an IND safety report of potential serious 
risks from clinical trials or any other source, as soon as possible, in accordance to 21 CFR Part 
312.32. 
All serious events will be reported to the FDA at least annually in a summary format.
8.8
SPONSOR PROTOCOL DEVIATION REPORTING
A Protocol Deviation is defined as any non-compliance with the clinical trial Protocol, Manual of 
Operational Procedures (MOP) and other Sponsor approved study related documents, GCP, or 
protocol-specific procedural requirements on the part of the participant, the Investigator, or the 
study site staff inclusive of site personnel performing procedures or providing services in support 
of the clinical trial.
It is the responsibility of the study Staff to document any protocol deviation identified by the Staff 
or the site Monitor in the CCR Protocol Deviation Tracking System (PDTS) online application. 
The entries into the PDTS online application should be timely, complete, and maintained per CCR 
PDTS user requirements. 
In addition, any deviation to the protocol should be documented in the participant’s source records 
and reported to the reviewing IRB per their guidelines. OSRO required protocol deviation 
reporting is consistent with E6(R2) GCP: Integrated Addendum to ICH E6(R1): 4.5 Compliance 
with Protocol; 5.18.3 (a), and 5.20 Noncompliance; and ICH E3 16.2.2 Protocol deviations.
9
CLINICAL MONITORING
Clinical site monitoring is conducted to ensure:
•
that the rights of the participants are protected, 
•
that the study is implemented per the approved protocol, Good Clinical Practice and 
standard operating procedures; and 
•
that the quality and integrity of study data and data collection methods are maintained.
Monitoring for this study will be performed by NCI CCR Office of Sponsor and Regulatory 
Oversight (OSRO) Sponsor and Regulatory Oversight Support (SROS) Services contractor. 
Clinical site monitoring activities will be based on OSRO standards, FDA Guidance E6(R2) Good 
Clinical Practice: Integrated Addendum to ICH E6(R1) March 2018, and applicable regulatory 
requirements.
Details of clinical site monitoring will be documented in a Clinical Monitoring Plan (CMP) 
developed by OSRO. CMPs will be protocol-specific, risk-based and tailored to address human 

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subject protections and integrity of the study data. OSRO will determine the intensity and 
frequency of monitoring will be based on several factors, including study type, phase, risk, 
complexity, expected enrollment rate, and any unique attributes of the study and the site. The 
Sponsor will conduct a periodic review of the CMP to confirm the plan's continued 
appropriateness. A change to the protocol, significant or pervasive non-compliance with GCP, or 
the protocol may trigger CMP updates.
OSRO SROS Monitoring visits and related activities will be conducted throughout the life cycle 
of each protocol. The first activity is before the study starts to conduct a Site Assessment Visit 
(SAV) (as warranted), followed by a Site Initiation Visit (SIV), Interim Monitoring Visit(s) 
(IMVs), and a study Close-Out Visit (COV).
Some monitoring activities may be performed remotely, while others will take place at the study 
site(s).  Monitoring visit reports will describe visit activities, observations, findings of protocol 
non-adherence and associated action items or follow-up required for resolution of findings.  
Monitoring reports will be distributed to the study PI, NCI CCR QA, coordinating center (if 
applicable) and the OSRO regulatory file.
The site Monitor will inform the study team of any deviations observed during monitoring visits. 
If unresolved, the Monitor will request that the site Staff enter the deviations in the CCR Protocol 
Deviation Tracking System (PDTS) for deviation reporting to the Sponsor and as applicable per 
institutional and IRB guidance.
10 STATISTICAL CONSIDERATIONS  
10.1 OBJECTIVES AND ENDPOINTS
OBJECTIVES
ENDPOINTS
JUSTIFICATION FOR 
ENDPOINTS
Primary
Phase 1: To determine the MTD, 
RP2D, and the safety and toxicity 
profile of the combination of 
VIP152 with venetoclax and 
prednisone (VVIP) in 
relapsed/refractory lymphoid 
malignancies
Adverse events assessed during the 
first 22 days of treatment for 
unsolicited events, and on Day 9 and 
15 of Cycle 1 for solicited events
Standard endpoint for 
phase I trial, see 
Section 3.1.1
Phase 2: To determine the CR rate 
of the combination of VIP152 with 
venetoclax and prednisone (VVIP) 
in R/R lymphoid malignancies
Complete response (CR) rate after 
cycles 6 and 12 of therapy  (+/-7 
days)
Standard endpoints for 
cancer clinical trials. 
Secondary
To assess the activity (ORR, 
TTR, DOR, EFS, PFS and OS) 
of VIP152 in combination with 
venetoclax and prednisone 
(VVIP) in relapsed/refractory 
lymphoid malignancies
- Overall survival (OS)- median, 
assessed during treatment and after 
completion of therapy until death or 
last follow-up q3, 4, 6 and 12 
months for post-treatment years 1, 
2, 3, and 4-5, for up to 5 years after 
the last participant has enrolled on 
study 
Standard endpoints for 
cancer clinical trials. 
Success of regimens 
will be determined by 
these endpoints

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OBJECTIVES
ENDPOINTS
JUSTIFICATION FOR 
ENDPOINTS
- Event free survival (EFS)- median, 
assessed during treatment and after 
completion of therapy until 
alternative treatment, 
relapse/progression, death or last 
follow-up q3, 4, 6 and 12 months 
for post-treatment years 1, 2, 3, and 
4-5, respectively, for up to 5 years 
after the last participant has enrolled 
on study 
- Progression free survival (PFS) - 
median, assessed during treatment 
and after completion of therapy 
until relapse/progression, death or 
last follow-up q3, 4, 6 and 12 
months for post-treatment years 1, 
2, 3, and 4-5, respectively, for up to 
5 years after the last participant has 
enrolled on study 
- Duration of Response (DOR)- 
median, assessed during therapy 
and after completion of therapy 
until progression or last follow-up 
q3, 4, 6 and 12 months for post-
treatment years 1, 2, 3, and 4-5, 
respectively, for up to 5 years after 
the last participant has enrolled on 
study 
- Time to Response (TTR)- median, 
assessed during therapy and after 
completion of therapy from 
initiation of therapy to first response 
q3, 4, 6 and 12 months for post-
treatment years 1, 2, 3, and 4-5, 
respectively, for up to 5 years after 
the last participant has enrolled on 
study 
- Overall Response Rate (ORR) 
assessed after cycles 6 and 12 of 
therapy (+/-7 days)
Exploratory 
To assess the ORR and CR rate 
to VVIP rechallenge in 
participants who achieve CR, 
discontinue therapy after 12 
cycles and subsequently relapse 
more than 6 months after initial 
study drug discontinuation
- Overall Response Rate (ORR) after 
rechallenge assessed after cycles 6 
and 12 of therapy (+/-7 days)
- CR after rechallenge assessed after 
cycles 6 and 12 of therapy (+/-7 
days)
Standard endpoints for 
cancer clinical trials

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OBJECTIVES
ENDPOINTS
JUSTIFICATION FOR 
ENDPOINTS
To assess circulating tumor 
DNA (ctDNA) response and 
correlate with molecular tumor 
analysis
To evaluate biomarkers of 
sensitivity or resistance to 
VIP152, venetoclax and 
prednisone
To assess the pharmacokinetics 
and pharmacogenomics of 
VIP152, venetoclax, and 
prednisone when given in 
combination
Each of these will be evaluated using 
descriptive methods and reported as 
exploratory results. If any statistical 
tests are performed in these analyses, 
the results will be presented without 
adjustment for multiple comparisons 
but reported in the context of the 
number of tests performed. See 
Section for 5.1 collection timepoints.
Exploratory analysis
10.2 SAMPLE SIZE DETERMINATION
10.2.1 Phase 1
The trial will begin with a Phase 1 evaluation of the combination of agents, with VIP152 and 
venetoclax evaluated at four dose escalation levels. Using a standard 3+3 design, up to 4 x 6=24 
participants may be required for the Phase 1 portion of the trial.
10.2.2 Phase 2
For the Phase 2 portion of the trial, participants will be accrued in three cohorts:
•
Cohort 1: R/R MYC-rearranged DLBCL/HGBCL
•
Cohort 2: R/R non-GCB DLBCL (no MYC rearrangement)
•
Cohort 3: R/R PTCL
The following are the sample size determination rules for each of the four cohorts based on the 
rate of CR from historic studies of venetoclax monotherapy in DLBCL (see Section 1.2.2.1.2) and 
other FDA-approved targeted therapies for PTCL (see Section 1.2.1.2):
10.2.2.1 MYC-rearranged DLBCL/HGBCL
In participants with MYC-rearranged DLBCL/HGBCL, it will be desirable if the fraction who 
experience a CR after 6 cycles of VVIP therapy were at least 20%. To obtain an acceptable 
outcome with small numbers of participants, the trial will be conducted using a Simon two-stage 
optimal design which will have as its objective to rule out a 12% CR rate (p0=0.12) in favor of an 
improvement of the CR rate to 30% (p1=0.30).  With alpha=0.10 (probability of accepting a poor 
treatment=0.10) and beta=0.20 (probability of rejecting a good treatment=0.20), the first stage will 
enroll 10 evaluable participants, and if 0 or 1 of the 10 have a CR after 6 cycles of VVIP therapy, 
then no further participants will be accrued in this cohort. If 2 or more of the first 10 participants 
have a CR after 6 cycles of VVIP therapy, then accrual would continue until a total of 29 evaluable 
participants have been treated. As it may take up to several months to determine if a participant 
has experienced a CR, a temporary pause in the accrual may be necessary to ensure that enrollment 
to the second stage is warranted.  In addition, if needed to allow time to evaluate the CR rate of 
the first stage, the study will allow up to 2 additional participants to be accrued pending 
determination of the CR rate in the initial 10 participants enrolled in the cohort. These 2 

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participants would not be included among the initial 10, but rather are a limited size addition and 
considered part of an intended second stage to permit evaluation without substantial disruption to 
accrual within the cohort. If there are only 1-5 participants with a CR after 6 cycles of VVIP 
therapy out of 29 participants, this would be an uninterestingly low CR rate. If there were 6 or 
more of 29 (20.7%) who experienced a CR after 6 cycles of VVIP therapy, this would be 
sufficiently interesting to warrant further study in later trials. Under the null hypothesis (12% CR 
rate), the probability of early termination is 65.8%.
10.2.2.2 Non-GCB DLBCL (no MYC-rearrangement)
In participants with non-GCB DLBCL without MYC rearrangements it will be desirable if the 
fraction who experience a CR after 6 cycles of VVIP therapy were at least 20%. To obtain an 
acceptable outcome with small numbers of participants, the trial will be conducted using a Simon 
two-stage optimal design which will have as its objective to rule out a 12% CR rate (p0=0.12) in 
favor of an improvement of the CR rate to 30% (p1=0.30).  With alpha=0.10 (probability of 
accepting a poor treatment=0.10) and beta=0.20 (probability of rejecting a good treatment=0.20), 
the first stage will enroll 10 evaluable participants, and if 0 or 1 of the 10 have a CR after 6 cycles 
of VVIP therapy, then no further participants will be accrued in this cohort. If 2 or more of the first 
10 participants have a CR after 6 cycles of VVIP therapy, then accrual would continue until a total 
of 29 evaluable participants have been treated. As it may take up to several months to determine 
if a participant has experienced a CR, a temporary pause in the accrual may be necessary to ensure 
that enrollment to the second stage is warranted.  In addition, if needed to allow time to evaluate 
the CR rate of the first stage, the study will allow up to 2 additional participants to be accrued 
pending determination of the CR rate in the initial 10 participants enrolled in the cohort. These 2 
participants would not be included among the initial 10, but rather are a limited size addition and 
considered part of an intended second stage to permit evaluation without substantial disruption to 
accrual within the cohort. If there are only 1-5 participants with a CR after 6 cycles of VVIP 
therapy out of 29 participants, this would be an uninterestingly low CR rate. If there were 6 or 
more of 29 (20.7%) who experienced a CR after 6 cycles of VVIP therapy, this would be 
sufficiently interesting to warrant further study in later trials. Under the null hypothesis (12% CR 
rate), the probability of early termination is 65.8%.
10.2.2.3 PTCL
In participants with PTCL it will be desirable if the fraction who experience a CR after 6 cycles of 
VVIP therapy were at least 20%. To obtain an acceptable outcome with small numbers of 
participants, the trial will be conducted using a Simon two-stage optimal design which will have 
as its objective to rule out a 12% CR rate (p0=0.12) in favor of an improvement of the CR rate to 
30% (p1=0.30).  With alpha=0.10 (probability of accepting a poor treatment=0.10) and beta=0.20 
(probability of rejecting a good treatment=0.20), the first stage will enroll 10 evaluable 
participants, and if 0 or 1 of the 10 have a CR after 6 cycles of VVIP therapy, then no further 
participants will be accrued in this cohort. If 2 or more of the first 10 participants have a CR after 
6 cycles of VVIP therapy, then accrual would continue until a total of 29 evaluable participants 
have been treated. As it may take up to several months to determine if a participant has experienced 
a CR, a temporary pause in the accrual may be necessary to ensure that enrollment to the second 
stage is warranted. In addition, if needed to allow time to evaluate the CR rate of the first stage, 
the study will allow up to 2 additional participants to be accrued pending determination of the CR 
rate in the initial 10 participants enrolled in the cohort. These 2 participants would not be included 
among the initial 10, but rather are a limited size addition and considered part of an intended second 

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stage to permit evaluation without substantial disruption to accrual within the cohort. If there are 
only 1-5 participants with a CR after 6 cycles of VVIP therapy out of 29 participants, this would 
be an uninterestingly low CR rate. If there were 6 or more of 29 (20.7%) who experienced a CR 
after 6 cycles of VVIP therapy, this would be sufficiently interesting to warrant further study in 
later trials. Under the null hypothesis (12% CR rate), the probability of early termination is 65.8%.
10.2.3 Participant Accrual
The trial may require up to 24+29+29+29=111 evaluable participants. To allow for a small number 
of inevaluable participants and screen failures (15 screen failures and 4 inevaluable), the accrual 
ceiling will be set at 130 participants. It is expected that up to 1.5-2.5 years may be required to 
accrue the Phase 1 participants and the first stage of each of the four two-stage designs. The accrual 
rate in the second stage of each two-stage design will depend on the success identified during in 
the first stage.
10.3 POPULATIONS FOR ANALYSES
10.3.1 Evaluable for toxicity
Any participant who receives at least one dose of any study agent will be evaluable for toxicity 
within the appropriate dose level or in the expansion cohort. The DLT evaluation period will be the 
first cycle (i.e., cycle 1, day 1 to cycle 2, day 1 pre-dose). 
10.3.2 Evaluable for objective response 
All participants who have received at least 1 cycle of therapy and have had their disease re-
evaluated will be considered evaluable for response to combination VVIP therapy. Participants 
need to have completed baseline and follow-up scans for inclusion in response evaluations, 
except that any participants noted to have clinical progression without the follow-up scan will be 
noted as being non-responders.  Participants need to have completed baseline and follow-up 
scans following cycle 1 of therapy to be evaluable for response to the combination therapy. 
(NOTE: Participants who exhibit objective disease progression prior to the end of cycle 1 will also 
be considered evaluable).
10.3.3 Evaluable Non-Target Disease Response:  
Participants who have lesions present at baseline that are evaluable but do not meet the definitions 
of measurable disease, have received at least one cycle of therapy, and have had their disease re-
evaluated will be considered evaluable for non-target disease.  The response assessment is based 
on the presence, absence, or unequivocal progression of the lesions. 
10.4 STATISTICAL ANALYSES
10.4.1 General approach
In the Phase 1 dose-escalation cohort, the DLTs at each dose level will be reported according to 
type of toxicity identified at each dose level. 
In the Phase 2 expansion cohorts, the ORR and CR rate will be estimated based on participants 
treated at the RP2D, separately by cohort along with a two-sided 95% confidence interval.

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10.4.2 Analysis of primary endpoints
10.4.2.1 Phase 1 dose-escalation
The DLTs at each dose level will be reported according to type of toxicity identified at each dose 
level. Final analysis will be made at least 30 days after the last participant completes therapy. 
Any participants who are not evaluable for the toxicity evaluation will be replaced.
10.4.2.2 Phase 2 dose-expansion
The CR rate will be estimated based on participants treated at the RP2D, separately by cohort along 
with a two-sided 95% confidence interval.
10.4.3 Analysis of secondary endpoints
The ORR will be estimated based on participants treated at the RP2D, separately by cohort along 
with a two-sided 95% confidence interval.
TTR, DOR, EFS, PFS and OS will be determined separately by cohort using the Kaplan-Meier 
method. The median and a 95% confidence interval will be reported for each cohort.
10.4.4 Safety analyses
The primary endpoint is determination of DLTs. The toxicity grades identified will be reported by 
dose level. All participants who receive at least 1 dose of study medication will be evaluable for 
safety (see Section 6.3.1).
10.4.5 Baseline descriptive statistics
Participant characteristics will be provided by cohort.
10.4.6 Planned Interim analyses
10.4.6.1 Phase 1 to Phase 2  Interim analysis
After 6 participants have completed the required DLT assessment period at the MTD or MAD 
(either completing the DLT evaluation period or experiencing DLT) with no more than 1 
participant experiencing DLT, a report including the supporting safety data and delineation of each 
criterion met, will be provided to the Sponsor (OSROSafety@nih.gov) before additional 
participants will be enrolled into the study. The Dose Escalation Determination form on the 
sponsor website: https://ccrod.cancer.gov/confluence/display/CCRCRO/Forms+and+Instructions 
may be used for this purpose.
If more than 1 participant has experienced DLT at DL1, no further accrual will occur. 
10.4.6.2 Interim efficacy analysis
As indicated in section 10.2.2, enrollment for efficacy evaluation will take place in 2 stages for 
each cohort.  Specifically, the second stage of each cohort will be conducted only if there are at 
least 2 of 10 participants with a complete response (Cohorts 1-3, NHL) after 6 cycles of study 
therapy. 
After the completion of disease assessment in cycle 6 (or earlier if progression confirmed sooner) 
in the 10th evaluable participant in each cohort, an analysis will be conducted. As addressed in 
section 10.2.2, up to 2 participants in the cohort being analyzed may be enrolled as the analysis is 
conducted. A brief interim analysis report will be created to document the number of responses in 
the first stage for the cohort under review, and will be reviewed by the PI and study team. The 

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interim analysis report will be provided to study sponsor prior to continuation of accrual. 
Alternatively, if the required number of responses is observed before that time, the interim analysis 
report may be generated, reviewed and provided to the study sponsor at that point without 
restrictions to accrual.  Interim safety analysis
Notable toxicities of venetoclax-based combination regimens include the development of clinical 
tumor lysis syndrome (TLS) as well as increased infectious complications that can be life-
threatening or fatal.  As an additional measure of safety across the entire study population, study-
wide stopping rules for prohibitive toxicities throughout the duration of study treatment will be 
utilized as per below:
•
If within the first 25 total participants who have been treated on study, 3 or more have 
experienced grade 3-4 clinical TLS or grade 4 infectious complications -or- if after 26 or 
more participants have been treated on study the cumulative incidence of grade 3-4 clinical 
TLS or grade 4 infectious complications exceeds 10%, then further enrollment to study 
will be held pending an amendment to modify study treatment.
•
If anytime 1 or more within the first 25 participants, 2 or more within the first 50 patients, 
3 or more within the first 75 participants, or 4 or more of all study participants treated 
experience a grade 5 treatment-emergent adverse event (TEAE), then further enrollment to 
study will be held pending an amendment to modify study treatment.
All SAEs and grade 5 TEAEs will be expeditiously reported to the study sponsor (CCR)as directed 
in Sections 8.3 . With any grade 5 TEAE, a temporary pause in enrollment will be considered, with 
resumption of study enrollment after thorough discussion and evaluation with the study sponsor 
(CCR). The sponsor may also consult with Vincerx Pharma (regarding VIP152 safety trends) as 
necessary. 
10.4.7 Subgroup analyses
Analyses will be done according to disease cohort.
10.4.8 Tabulation of individual participant data
None are planned.
10.4.9 Analysis of exploratory endpoints
Any analyses performed on the exploratory objectives are done without any formal adjustment for 
multiple comparisons but in the context of the number of tests performed.
11 COLLABORATIVE AGREEMENTS
11.1 COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT
This study has been approved by Vincerx (CRADA #03459) who will provide study drug for the 
participants enrolled on the study and funding to purchase commercial supply of venetoclax 
(presently manufactured by AbbVie).

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12 HUMAN SUBJECTS PROTECTIONS 
12.1 RATIONALE FOR PARTICIPANT SELECTION
All participants from both sexes and all racial/ethnic groups are eligible for this study if they meet 
the eligibility criteria outlined in the protocol. Participants with HIV infection will be excluded 
because the unknown effects of the combination targeted therapy on the underlying HIV infection 
are unknown and could be adverse. In addition, these participants are at increased risk of lethal 
infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken 
in participants receiving combination antiretroviral therapy when indicated. In addition, pregnant 
individuals and individuals unwilling to stop nursing are excluded because of the potential teratogenic 
effects of therapy.
12.2 PARTICIPATION OF CHILDREN
Participants under the age of 18 are excluded because recurrent mature lymphoid malignancies are 
rare in young participants, and the inclusion of an occasional younger participant will not provide 
generalizable information that would justify their inclusion on this study. NOTE: Because no 
dosing or adverse event data are currently available on the use of VIP152 and venetoclax in 
participants <18 years of age, children are excluded from this study, but will be eligible for future 
pediatric trials.
12.3 RISK/BENEFIT ASSESSMENT
12.3.1 Known Potential Risks
12.3.1.1 Study Drug Risks
The main risks associated with the study agents include hematologic side effects (neutropenia, 
thrombocytopenia, anemia and leukopenia), gastrointestinal (diarrhea, nausea, vomiting, 
constipation), constitutional (fatigue) and infection. Serious side effects requiring hospitalization 
are possible including tumor lysis syndrome, neutropenic fever and severe infusion reactions. 
Additional toxicity may be seen with the combination of these study agents that was not seen with 
monotherapy or prior combination trials. Additional toxicity may be seen with the combination of 
these study agents that was not seen with monotherapy or prior combination trials. See Section 
14.
12.3.1.2 Biopsy risks
The risks associated with biopsies are pain, redness, welling, bruising and/or bleeding at the biopsy 
site. In order to minimize pain, conscious sedation will be used.  Biopsies for research purposes 
are optional on this study. Rarely, there is a risk of infection at the sampling site. 
12.3.1.3 Conscious sedation
The common side effects of conscious sedation include drowsiness, delayed reflexes, hypotension, 
headache, and nausea.  These are generally mild and last no more than a few hours.
12.3.1.4 Risks of Imaging
CT, PET, and/ or MRI scans may be used to monitor a participant’s disease on this study.  CT and 
PET scans expose a participant to radiation; the amount depends on the number of body areas 
scanned. In addition, CT, PET and MRI scans involve use of contrast (oral and/or IV).  An IV line 
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the IV is placed.  There is also a small risk of bruising or infection. If a contrast agent is given with 
the scan there is a small risk of having a reaction to the contrast. In addition, there is a risk of 
kidney damage from the contrast agent (gadolinium) used for the MRI scan. In the small group of 
participants who have a reaction, the most common symptoms are nausea, pain in the vein where 
the contrast was given, headache, a metallic or bitter taste in the mouth, and a warm or flushing 
feeling that lasts from 1-3 minutes.  Rarely, these symptoms may require treatment.  In very rare 
cases, people have had more severe allergic reactions that result in skin rashes, shortness of breath, 
wheezing, or lowering of the blood pressure.  
12.3.1.5 Radiation
This study will involve radiation from the following sources:
•
Up to 10 CT scans of neck, chest, abdomen, and pelvis including 1 done at screening
•
Up to 3 whole body 18F-FDG PET/CT scans including 1 done at screening
•
Up to 2 CT scans for CT-guided biopsies
The maximum exposure in one year is 18.2 rem. This amount is more than would be expected 
from everyday background radiation. Being exposed to excess radiation can increase the risk of 
cancer. The risk of getting cancer from the radiation exposure in this study is 1.8 out of 100 (1.8%) 
and of getting a fatal cancers is 0.9 out of 100 (0.9%).
12.3.1.6 Risks related to blood sampling
Side effects of blood draws include pain and bruising, lightheadedness, and rarely, fainting, blood 
clot formation at the needle insertion site or infection of the vein. The maximum amount of blood 
that will be drawn at a single timepoint on study is approximately 95 mL.  The maximum amount 
of blood that will be drawn over 8 weeks on the study is approximately 616.5 mL.
12.3.1.7 Risk of Urine Collection
There are no physical risks associated with urine collection.
12.3.1.8 Risks of EKG and ECHO
Side effects of EKG and ECHO are skin irritation where electrodes are placed.
12.3.1.9 Risks of Bone Marrow Biopsy
Bone marrow biopsy is minimally invasive and is typically a very safe procedure. Usually the 
hipbone is numbed with anesthesia. Using a needle, the solid and liquid portion of bone marrow 
is taken out. This procedure causes some pain. Very rarely, infection or bleeding may occur at the 
needle site.
12.3.1.10
Non-Physical Risks of Genetic Research
Risk of receiving unwanted information:
Anxiety and stress may arise as a result of the anticipation that unwanted information regarding 
disease related DNA sequencing or disease tendencies, or misattributed paternity. Subjects will 
be clearly informed that the data related to DNA sequencing and genetic analysis is coded, 
investigational and will not be shared with subject’s, family members or health care providers.
Risk related to possibility that information may be released:
This includes the risk that data related to genotype, DNA sequencing or risk for disease 
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enforcement agencies. Although there are no plans to release results to the participants, family 
members or health care providers, this risk will be included in the informed consent document.
Risk to family or relatives:
Family members or relatives may or may not want to be aware of familial tendencies or genetic 
risks of disease which may cause anxiety about possible future health problems. As previously 
noted, subjects will be notified of any medically significant and actionable incidental findings. 
Study results will not be shared with subjects.
12.3.2 Known Potential Benefits
Venetoclax has shown clinical activity both as monotherapy and as combination therapy in 
participants with relapsed or refractory lymphoid malignancies It is possible that the combination 
of venetoclax and VIP152 may synergistically enhance the anti-tumor activity of the other with 
the hope of increasing efficacy of these agents and decreasing the development of treatment 
resistance.
12.3.3 Assessment of Potential Risks and Benefits
A number of clinically appropriate strategies to minimize risks to participants have been built into 
the protocol through the means of inclusion/exclusion criteria, monitoring strategies, and 
management guidelines. It is possible that treatment on this protocol may reduce cancer burden or 
lessen symptoms caused by cancer. While treatment on this protocol may not individually benefit 
participants, the knowledge gained from this study may help others in the future who have this 
cancer. Potential risks include the possible occurrence of any of a range of side effects listed above. 
12.4 CONSENT PROCESS AND DOCUMENTATION
The informed consent document will be provided as a physical or electronic document to the 
participant for review prior to consenting.  A designated study investigator* will carefully explain 
the procedures and tests involved in this study, and the associated risks, discomforts and benefits. 
In order to minimize potential coercion, as much time as is needed to review the document will be 
given, including an opportunity to discuss it with friends, family members and/or other advisors, 
and to ask questions of any designated study investigator. A signed informed consent document 
will be obtained prior to entry onto the study. 
The initial consent process as well as re-consent, when required, may take place in person or 
remotely (e.g., via telephone or other NIH approved remote platforms used in compliance with 
local policy, including HRPP Policy 303) per discretion of the designated study investigator and 
with the agreement of the participant.  Whether in person or remote, the privacy of the subject will 
be maintained. Consenting investigators (and participant, when in person) will be located in a 
private area (e.g., clinic consult room). When consent is conducted remotely, the participant will 
be informed of the private nature of the discussion and will be encouraged to relocate to a more 
private setting if needed.  
Consent will be documented with required signatures on the physical document (which includes 
the printout of an electronic document sent to participant) or as described below, with a manual 
(non-electronic) signature on the electronic document.  When required, witness signature will be 
obtained similarly as described for the investigator and participant.

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Manual (non-electronic) signature on electronic document:
When a manual signature on an electronic document is used for the documentation of consent 
at the NIH Clinical Center, this study will use the following to obtain the required signatures:
•
Adobe platform (which is not 21 CFR Part 11 compliant); or,  
•
iMedConsent platform (which is 21 CFR Part 11 compliant)
During the consent process, participants and investigators will view individual copies of 
the approved consent document on screens at their respective locations (if remote consent); 
the same screen may be used when in the same location, but is not required.  
Both the investigator and the participant will sign the document using a finger, stylus or 
mouse. 
Note: Refer to the CCR SOP PM-2, Obtaining and Documenting the Informed Consent Process 
for additional information (e.g., verification of participant identity when obtaining consent 
remotely) 
found 
at: 
https://nih.sharepoint.com/sites/NCI-CCR-OCD-
Communications/SitePages/OEC-Administrative---Clinical-Research-
(ADCR).aspx?Mode=Edit..
*Please note that consent for treatment must be obtained by a designated appropriately licensed 
study investigator (e.g., MD, NP, PA, DO). However, study investigators not falling into this 
category (e.g. RNs) who are designated as able to obtain consent, may do so for non-treatment 
procedures such as screening.
For the optional research biopsies on the protocol, the participant will consent at the time of the 
procedure (via clinical procedure consent form). If the participant refuses the optional biopsy at 
that time, the refusal will be documented in the medical record and in the research record.
13 REGULATORY AND OPERATIONAL CONSIDERATIONS 
13.1 STUDY DISCONTINUATION AND CLOSURE
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause.  Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
associate investigators, the Investigational New Drug (IND) sponsor and regulatory authorities.  If 
the study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly 
inform study participants, the Institutional Review Board (IRB), and sponsor and will provide the 
reason(s) for the termination or suspension.  Study participants will be contacted, as applicable, 
and be informed of changes to study visit schedule.
Circumstances that may warrant termination or suspension include, but are not limited to:
•
Determination of unexpected, significant, or unacceptable risk to participants
•
Demonstration of efficacy that would warrant stopping   
•
Insufficient compliance to protocol requirements
•
Data that are not sufficiently complete and/or evaluable
•
Determination that the primary endpoint has been met
•
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Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB and as applicable, Food and Drug Administration (FDA).
13.2 QUALITY ASSURANCE AND QUALITY CONTROL
The clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion.  An individualized quality management plan 
will be developed to describe a site’s quality management.
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution.
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical 
trial is conducted and data are generated and biological specimens are collected, documented 
(recorded), and reported in compliance with the protocol, International Council for Harmonisation 
Good Clinical Practice (ICH GCP), and applicable regulatory requirements (e.g., Good Laboratory 
Practices (GLP), Good Manufacturing Practices (GMP)). 
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
regulatory authorities.
13.3 CONFLICT OF INTEREST POLICY
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical.  Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and 
managed. Furthermore, persons who have a perceived conflict of interest will be required to have 
such conflicts managed in a way that is appropriate to their participation in the design and conduct 
of this trial.  The study leadership in conjunction with the NIH has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest.
13.4 CONFIDENTIALITY AND PRIVACY
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor(s). This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to participants. Therefore, 
the study protocol, documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study or the data will be released to any unauthorized 
third party without prior written approval of the sponsor. 
All research activities will be conducted in as private a setting as possible.
The study monitor, other authorized representatives of the sponsor, representatives of the 
Institutional Review Board (IRB), and/or regulatory agencies may inspect all documents and 
records required to be maintained by the investigator, including but not limited to, medical records 
(office, clinic, or hospital) and pharmacy records for the participants in this study. The clinical 
study site will permit access to such records.
The study participant’s contact information will be securely stored at the/each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a secure 

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location for as long a period as dictated by the reviewing IRB, Institutional policies, or sponsor 
requirements.
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
will be stored at the NCI CCR. This will not include the participant’s contact or identifying 
information. Rather, individual participants and their research data will be identified by a unique 
study identification number. The study data entry and study management systems used by the 
clinical site(s) and by NCI CCR research staff will be secured and password protected. At the end 
of the study, all study databases will be archived at the NIH.
To further protect the privacy of study participants, a Certificate of Confidentiality has been issued 
by the National Institutes of Health (NIH).  This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any civil, 
criminal, administrative, legislative, or other proceeding, whether at the federal, state, or local 
level. By protecting researchers and institutions from being compelled to disclose information that 
would identify research participants, Certificates of Confidentiality help achieve the research 
objectives and promote participation in studies by helping assure confidentiality and privacy to 
participants.
14 PHARMACEUTICAL INFORMATION/ DEVICE INFORMATION    
14.1 VENETOCLAX
14.1.1 Source
Venetoclax is a commercially available agent and will be purchased by the CCR and supplied to 
the participants enrolled on the study by the NIH clinical center pharmacy department. 
14.1.2 Toxicity
Please see venetoclax prescribing information for additional details. The major adverse events 
observed in clinical studies are TLS, neutropenia, infections, embryo-fetal toxicity and concerns 
over immunization with live attenuated vaccines. 
14.1.3 Formulation and Preparation
Venetoclax comes in 10 mg, 50 mg and 100 mg tablets. Excipients include: copovidone, 
colloidal silicon dioxide, polysorbate 80, sodium stearyl fumarate, calcium phosphate dibasic. 
In addition, the 10 mg and 100 mg tablet coating contains iron oxide yellow, polyvinyl alcohol, 
titanium dioxide, polyethylene glycol, and talc; the 50 mg tablet coating contains iron oxide 
yellow, iron oxide red, iron oxide black, polyvinyl alcohol, titanium dioxide, polyethylene 
glycol, and talc.
14.1.4 Stability and Storage
Venetoclax tablets will be packaged in high-density polyethylene plastic bottles to 
accommodate the study design. Each bottle will be labeled per local regulatory requirements. 
A desiccant canister may be included in the bottle.  The tablets must be stored in original 
container  at or below 30C (86F). If supplied with a desiccant, the desiccant canister should 
be returned to the bottle directly after each tablet removal.

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14.1.5 Administration Procedures
Administration with a low-fat meal increased venetoclax exposure by approximately 3.4-fold, 
and administration with a high-fat meal increased venetoclax exposure by 5.1- to 5.3-fold 
compared to fasting conditions. Venetoclax should be administered with a meal.
Venetoclax should be taken with a meal and may be administered with prednisone. If vomiting 
occurs within 15 minutes after taking venetoclax and all expelled tablets are still intact, another 
dose may be given. Otherwise, no replacement dose is to be given. In cases where a dose of 
venetoclax is missed or forgotten, the participant should take the dose as soon as possible and 
ensure that the minimal interval between the current dose and the next dose is at least 16 hours 
in order to avoid excessive drug accumulation after the next dose.
Venetoclax will be dispensed to participants in bottles. All doses of venetoclax taken in the 
clinic or day hospital should be taken from the bottle dispensed to the participant. Unused 
venetoclax tablets dispensed during previous visits must be returned to the site and drug 
accountability records must be updated. Returned tablets must not be re-dispensed to anyone. 
Participants should return all used bottles to the site when they receive new study drug.
All participants must receive prophylaxis for TLS (see Sections4.1.3 and Appendix C) prior to 
the initiation of venetoclax.
14.1.6 Incompatibilities
Venetoclax is a small molecule administered orally and is primarily metabolized by cytochrome 
P450 3A4 (CYP3A4). Concomitant use of venetoclax and strong inducers or inhibitors of 
CYP3A is contraindicated (see Appendix B, and Sections 4.2.1 and 4.3). Please refer to the 
package insert and PDR for full drug interactions and toxicities.
14.2 PREDNISONE
14.2.1 Source
Prednisone is commercially available and will be purchased by the CCR and supplied to the 
participants enrolled on the study by the NIH Clinical Center Pharmacy Department.
14.2.2 Toxicity
The most commonly reported toxicities have included insomnia; mood, appetite, and skin changes; 
gastrointestinal problems/pain; and headache, dizziness, and redistribution of body fat. Please refer 
to the package insert for a complete listing of all toxicities.
14.2.3 Formulation and Preparation
Prednisone is commercially available in oral pill and liquid formulations; it is intended that we 
will exclusively use the pill formulation in this study. All formulation excipients are compendial 
and are commonly used in oral formulations.
14.2.4 Stability and Storage
Prednisone will be packaged in opaque high-density polyethylene plastic bottles with labels 
bearing the appropriate label text as required by governing regulatory agencies. All supplied 
drug will be dispensed in child-resistant packaging.

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Please refer to the package insert for additional guidance on drug preparation, handling and 
storage.
14.2.5 Administration Procedures
Prednisone will be administered orally per the drug administration schedule in Section 3.2.
14.3 VIP152
14.3.1 Source
VIP152 will be provided by Vincerx and supplied to the participants enrolled on the study by the 
NIH clinical center pharmacy department. 
14.3.2 Toxicity
See Section 1.2.2.2.1. Generally, in phase 1 dose escalation studies, the most commonly 
reported toxicities were neutropenia and gastrointestinal toxicity. The observed toxicity seen so 
far has been manageable with anti-emetics and G-CSF.  
14.3.3 Formulation and Preparation
VIP152 drug substance is a white to slightly colored solid. It is practically insoluble in water, 
slightly soluble in 0.1 M hydrochloric acid (HCl) and ethanol and soluble in polyethylene glycol 
(PEG) 400. The solid drug substance is insensitive to thermal stress, non-hygroscopic and not 
sensitive to light. 
A sterile IV solution of VIP152 with a nominal concentration of 2.5 mg/mL has been developed. 
The solution is provided in 20 mL brown glass vials closed with a rubber stopper and a flanged 
closure; each vial contains a nominal fill volume of 16.0 mL. The solution may be diluted prior 
to administration using physiological saline solution (0.9% NaCl solution) for injection down 
to a concentration of 0.10 mg/mL. 
14.3.4 Stability and Storage
The transport and storage conditions at 2-8°C and protection from strong light are required. 
Please refer to pharmacy manual for details. 
14.3.5 Administration Procedures
Please refer to pharmacy manual to administration procedures. 
14.3.6 Incompatibilities
VIP152 is a small molecule administered via IV and is primarily metabolized by cytochrome 
P450 3A4 (CYP3A4). Concomitant use of VIP152 and strong inducers or inhibitors of CYP3A 
is contraindicated (see Appendix B, Sections 4.2.1 and 4.3). Please refer to the VIP152 IB for 
full drug interactions and toxicities.
14.4 ADDITIONAL INFORMATION
Guidelines for dosage modification and treatment interruption or discontinuation are provided 
in Section 3.3. Treatment will continue for up to 12 cycles of treatment [in those who achieve 
CR], up to a maximum of 24 total cycles of treatment, until disease progression, or other reason 
for treatment discontinuation as outlined in Section 3.7.

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Investigators are prohibited from supplying study drug to any participants not properly enrolled 
in this study or to any physicians or scientists except those designated as sub-investigators on 
Food and Drug Administration (FDA) Form 1572. The investigator must ensure that 
participants receive study drug only from personnel who fully understand the procedures for 
administering the drug.
All doses of oral study drugs taken in the clinic or day hospital should be taken from the bottle 
dispensed to the participant. Unused tablets/capsules dispensed during previous visits must be 
returned to the site and drug accountability records must be updated; returned supply must not 
be re- dispensed to anyone. Participants should return all used bottles to the site when they 
receive new study drug.
For the purpose of drug accountability of oral agents, empty bottles and returned drug may be 
handled per local institution policy; unless otherwise noted above or in an applicable Pharmacy 
Manual.
14.5 VYSIS LSI MYC BREAK APART REARRANGEMENT PROBE KIT
MYC rearrangement FISH testing is performed using the Vysis LSI MYC Break Apart 
Rearrangement Probe (Abbott Molecular, Inc.) in the Chromosome Pathology Section, Laboratory 
of Pathology, CCR, NCI. This kit is not FDA approved. It is being used as a treatment determining 
in-vitro diagnostic device in this study. According to 21 CFR 812.3(m), a significant risk device 
presents a potential for serious risk to the health, safety and welfare of a participant and meets the 
significant risk criteria listed in the table below along with the sponsor’s conclusions with regard 
to the applicability of these criteria to the current study. The device has been assessed by the 
sponsor as non-significant risk per the below.
Significant Risk Criteria
Applicable to 
current study
Justification
Is an implant
No
The Vysis LSI MYC Break Apart 
Rearrangement Probe Kit is not introduced 
into the participant.
Is used in supporting or 
sustaining human life
No
The device is diagnostic.
Is of substantial importance 
in diagnosing mitigating or 
treating disease or preventing 
impairment of human health
No
While the device is diagnostic, we do not 
believe it presents a potential for serious 
risk to the health and welfare of the 
participant. The assessment of MYC 
rearrangement is only used to help to 
increase the possibility that all persons 
enrolling on the study might derive benefit 
from study therapy. 
Otherwise poses a risk
No
Testing will be performed on archival 
samples or on fresh sample that is collected 
at screening for confirmation of diagnosis.  
No additional collection of sample will 
occur for purposes of MYC testing.

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15 REFERENCES 
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Confirmation of the molecular classification of diffuse large B-cell lymphoma by 
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2.
Akyurek N, Uner A, Benekli M, Barista I. Prognostic significance of MYC, BCL2, and 
BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with 
cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab. Cancer. 
2012;118(17):4173-83.
3.
Rosenwald A, Bens S, Advani R, Barrans S, Copie-Bergman C, Elsensohn M-H, et al. 
Prognostic Significance of MYC Rearrangement and Translocation Partner in Diffuse Large B-
Cell Lymphoma: A Study by the Lunenburg Lymphoma Biomarker Consortium. Journal of 
Clinical Oncology. 2019;37(35):3359-68.
4.
Savage KJ, Johnson NA, Ben-Neriah S, Connors JM, Sehn LH, Farinha P, et al. MYC 
gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma 
patients treated with R-CHOP chemotherapy. Blood. 2009;114(17):3533-7.
5.
Bartlett NL, Wilson WH, Jung SH, Hsi ED, Maurer MJ, Pederson LD, et al. Dose-
Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell 
Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. 
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 
2019;37(21):1790-9.
6.
Dunleavy K, Fanale MA, Abramson JS, Noy A, Caimi PF, Pittaluga S, et al. Dose-
adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and 
rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement: a 
prospective, multicentre, single-arm phase 2 study. The Lancet Haematology. 2018;5(12):e609-
e17.
7.
Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, et al. Salvage 
regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab 
era. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 
2010;28(27):4184-90.
8.
Crump M, Neelapu SS, Farooq U, Van Den Neste E, Kuruvilla J, Westin J, et al. 
Outcomes in refractory diffuse large B-cell lymphoma: results from the international 
SCHOLAR-1 study. Blood. 2017;130(16):1800-8.
9.
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. 
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. New 
England Journal of Medicine. 2017;377(26):2531-44.
10.
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. 
Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. New 
England Journal of Medicine. 2018;380(1):45-56.
11.
Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 
revision of the World Health Organization classification of lymphoid neoplasms. Blood. 
2016;127(20):2375-90.
12.
Vose J, Armitage J, Weisenburger D. International peripheral T-cell and natural killer/T-
cell lymphoma study: pathology findings and clinical outcomes. Journal of clinical oncology : 
official journal of the American Society of Clinical Oncology. 2008;26(25):4124-30.

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13.
Adams SV, Newcomb PA, Shustov AR. Racial Patterns of Peripheral T-Cell Lymphoma 
Incidence and Survival in the United States. Journal of clinical oncology : official journal of the 
American Society of Clinical Oncology. 2016;34(9):963-71.
14.
Chihara D, Fanale MA, Miranda RN, Noorani M, Westin JR, Nastoupil LJ, et al. The 
survival outcome of patients with relapsed/refractory peripheral T-cell lymphoma-not otherwise 
specified and angioimmunoblastic T-cell lymphoma. Br J Haematol. 2017;176(5):750-8.
15.
Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma 
incidence patterns by WHO subtype in the United States, 1992-2001. Blood. 2006;107(1):265-
76.
16.
Horwitz S, O'Connor OA, Pro B, Illidge T, Fanale M, Advani R, et al. Brentuximab 
vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a 
global, double-blind, randomised, phase 3 trial. Lancet. 2019;393(10168):229-40.
17.
Yang Y-T, Tai C-J, Chen C, Wu H-C, Mikhaylichenko N, Chiu H-T, et al. Highly 
Diverse Efficacy of Salvage Treatment Regimens for Relapsed or Refractory Peripheral T-Cell 
Lymphoma: A Systematic Review. PLoS One. 2016;11(10):e0161811-e.
18.
Davids MS, Roberts AW, Seymour JF, Pagel JM, Kahl BS, Wierda WG, et al. Phase I 
First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin 
Lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical 
Oncology. 2017;35(8):826-33.
19.
Lücking U, Kosemund D, Böhnke N, Lienau P, Siemeister G, Denner K, et al. Changing 
for the Better: Discovery of the Highly Potent and Selective CDK9 Inhibitor VIP152 Suitable for 
Once Weekly Intravenous Dosing for the Treatment of Cancer. J Med Chem. 
2021;64(15):11651-74.
20.
Hashiguchi T, Bruss N, Best S, Lam V, Danilova O, Paiva CJ, et al. Cyclin-Dependent 
Kinase-9 Is a Therapeutic Target in MYC-Expressing Diffuse Large B-Cell Lymphoma. Mol 
Cancer Ther. 2019;18(9):1520-32.
21.
Li L, Pongtornpipat P, Tiutan T, Kendrick SL, Park S, Persky DO, et al. Synergistic 
induction of apoptosis in high-risk DLBCL by BCL2 inhibition with ABT-199 combined with 
pharmacologic loss of MCL1. Leukemia. 2015;29(8):1702-12.
22.
Diamond JR, Moreno V, Lim EA, Cordoba R, Cai C, Ince SJ, et al. Phase I dose 
escalation study of the first-in-class selective PTEFb inhibitor BAY 1251152 in patients with 
advanced cancer: Novel target validation and early evidence of clinical activity. Journal of 
Clinical Oncology. 2018;36(15_suppl):2507-.
23.
Moreno V, Cordoba R, Morillo D, Diamond JR, Hamdy AM, Izumi R, et al. Safety and 
efficacy of VIP152, a CDK9 inhibitor, in patients with double-hit lymphoma (DHL). Journal of 
Clinical Oncology. 2021;39(15_suppl):7538-.
24.
Cidado J, Boiko S, Proia T, Ferguson D, Criscione SW, San Martin M, et al. AZD4573 Is 
a Highly Selective CDK9 Inhibitor That Suppresses MCL-1 and Induces Apoptosis in 
Hematologic Cancer Cells. Clinical cancer research : an official journal of the American 
Association for Cancer Research. 2020;26(4):922-34.
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Koch R, Christie AL, Crombie JL, Palmer AC, Plana D, Shigemori K, et al. Biomarker-
driven strategy for MCL1 inhibition in T-cell lymphomas. Blood. 2019;133(6):566-75.
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Melani C, Lakhotia R, Pittaluga S, Miljkovic MD, Phelan JD, Muppidi JR, et al. Phase 
1b/2 Study of Vipor (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide) in 
Relapsed/Refractory B-Cell Lymphoma: Safety, Efficacy and Molecular Analysis. Blood. 
2020;136:44-5.

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Morschhauser F, Feugier P, Flinn IW, Gasiorowski R, Greil R, Illés Á, et al. A phase 2 
study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell 
lymphoma. Blood. 2021;137(5):600-9.
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Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. 
Confirmation of the molecular classification of diffuse large B-cell lymphoma by 
immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275-82.

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16 ABBREVIATIONS
Abbreviation
Term
ABC
Activated B-cell
ACAT
Ability to Consent Assessment Team
AE
Adverse Event/Adverse Experience
AESI
Adverse Event/Experience of Special Interest
AITL
Angioimmunoblastic T-cell lymphoma
ALCL
Anaplastic large cell lymphoma
ALT
Alanine Aminotransferase
ANC
Absolute neutrophil count
ASCT
Autologous stem cell transplantation
AST
Aspartate Aminotransferase
AUC
Area under the curve
BAL
Bronchoalveolar lavage
BTK
Bruton’s tyrosine kinase
BTRIS
Biomedical Translational Research Information System
BV
Brentuximab vedotin 
CAP
CT chest, abdomen, and pelvis
CCR
Center for Cancer Research
CDA
Confidential Disclosure Agreement
CFR
Code of Federal Regulations
CI
Confidence Interval
CLL/SLL
chronic lymphocytic leukemia/small lymphocytic lymphoma 
CNS
Central nervous system
CNSL
CNS lymphomas
COO
Cell of Origin
CONSORT
Consolidated Standards of Reporting Trials
COV
Close-out Visit
CR
Complete Response
CrCl
Creatinine Clearance
CSF
Cerebrospinal fluid
CSR 
Clinical Study Report
CRADA
Cooperative Research and Development Agreement
CT
Computed Tomography
CTA
Clinical Trials Agreement
CTCAE
Common Terminology Criteria for Adverse Events
ctDNA
Circulating DNA
DLBCL
Diffuse large B-cell lymphoma  
DLT
Dose-limiting toxicity
DS
Double strength
DTA
Data Transfer Agreement
EATL
Enteropathy-associated T-cell lymphoma
EBV
Epstein Barr Virus

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Abbreviation
Term
EC
Ethics Committee
eCRF
Electronic Case Report Form
ECOG
Eastern Cooperative Oncology Group
EFS
Event-free survival
EKG
Electrocardiogram
ENKL
Extranodal NK/T cell lymphoma, nasal type
FDA
Food and Drug Administration
FISH
Fluorescent in situ hybridization
ICBP
Individuals of childbearing potential
FWA
Federal-Wide Assurance
GCP
Good Clinical Practice
GCB
Germinal Center B-cell
GDS
Genomic Data Sharing
GEP
Gene Expression Profiling 
GLP
Good Laboratory Practices
GMP
Good Manufacturing Practices
G-CSF
Granulocyte-colony-stimulating factor 
HBsAg
Hepatitis B surface antigen
HBV
Hepatitis B virus
HBcAb
Hepatitis B core antibody
HBsAb
Hepatitis B surface antibody
HCV
Hepatitis C virus
HCVAb
Hepatitis C antibody
HGBCL
High grade B-cell lymphoma
HHS
Health and Human Services
HIV
Human immunodeficiency virus
IB
Investigator’s Brochure
IBC
Institutional Biosafety Committee
ICD/ICF
Informed Consent Document/Form
ICH
International Council for Harmonisation
IMiD
immunomodulatory agent (IMiD)
IMV
Interim Monitoring Visit
IND
Investigational New Drug 
IRB
Institutional Review Board
IRBO
Institutional Review Board Office
IRR
Infusion related reactions
IV
Intravenous
LAR
Legally Authorized Representative
LD
Lactate dehydrogenase
LDH
Lactic dehydrogenase
MBL
Monoclonal B-cell lymphocytosis
MGUS
Monoclonal gammopathy of undetermined significance

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Abbreviation
Term
MM
Multiple Myeloma
MRI
Magnetic Resonance Imaging
MTD
Maximum Tolerated Dose
NCT
National Clinical Trial (number)
NHL
Non-Hodgkin lymphoma
NIH
National Institutes of Health
OHSRP
Office for Human Subjects Research Protections
OHRP
Office for Human Research Protections
OS
Overall survival
OSRO
Office of Sponsor and Regulatory Oversight
PCR
Polymerase chain reaction
PD
Progressive Disease
PET
Positron Emission Tomography
PFS
Progression-free survival
PI
Principal Investigator
PK
Pharmacokinetic
PR
Partial Response
PS
Performance Status
PTCL
Peripheral T-cell Lymphoma
PT
Prothrombin time
PTT
Partial thromboplastin time
QA
Quality Assurance
QC
Quality Control
R/R
Relapsed/Refractory
SAE
Serious Adverse Event/Serious Adverse Experience
SAV
Site Assessment Visit
SIV
Site Initiation Visit
SD
Stable Disease
SOP
Standard Operating Procedure
TEAE
Treatment-emergent adverse event 
TCM
T-cell malignancies
TLS
Tumor Lysis Syndrome
TSH
Thyroid stimulating hormone
TTR
Time to response
ULN
Upper limit of normal
US
United States
WBRT
Whole brain radiation
WHO
World Health Organization
VIPOR
Venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide
VVIP
Venetoclax, VIP152, prednisone
VTE
Venous thromboembolism

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17 APPENDIX
17.1 APPENDIX A: PERFORMANCE STATUS CRITERIA
ECOG Performance Status Scale
Karnofsky Performance Scale
Grade
Descriptions
Percent
Description
100
Normal, no complaints, no 
evidence of disease.
0
Normal activity. Fully active, able 
to carry on all pre-disease 
performance without restriction.
90
Able to carry on normal activity; 
minor signs or symptoms of 
disease.
80
Normal activity with effort; 
some signs or symptoms of 
disease.
1
Symptoms, but ambulatory. 
Restricted in physically strenuous 
activity, but ambulatory and able 
to carry out work of a light or 
sedentary nature (e.g., light 
housework, office work).
70
Cares for self, unable to carry on 
normal activity or to do active 
work.
60
Requires occasional assistance, 
but is able to care for most of 
his/her needs.
2
In bed <50% of the time. 
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities. Up and about 
more than 50% of waking hours.
50
Requires considerable assistance 
and frequent medical care.
40
Disabled, requires special care 
and assistance.
3
In bed >50% of the time. Capable 
of only limited self-care, confined 
to bed or chair more than 50% of 
waking hours.
30
Severely disabled, 
hospitalization indicated. Death 
not imminent.
20
Very sick, hospitalization 
indicated. Death not imminent.
4
100% bedridden. Completely 
disabled. Cannot carry on any 
self-care. Totally confined to bed 
or chair.
10
Moribund, fatal processes 
progressing rapidly.
5
Dead.
0
Dead.

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17.2 APPENDIX B: INHIBITORS AND INDUCERS OF CYP3A
Inhibitors of CYP3A are defined as follows. A comprehensive list of inhibitors can be found at the 
following website: 
http://medicine.iupui.edu/clinpharm/ddis/table.aspx.
. The general categorization into strong, moderate, and weak inhibitors according to the 
website is displayed below. Refer to Section 4.2.1 _bookmark52and 4.3 on instructions 
for concomitant use of CYP3A inhibitors and inducers with study medications.
Inhibitors of CYP3A
Inducers of CYP3A
Strong inhibitors:
INDINAVIR 
NELFINAVIR 
RITONAVIR 
CLARITHROMYCIN 
ITRACONAZOLE 
KETOCONAZOLE 
NEFAZODONE 
SAQUINAVIR 
TELITHROMYCIN
Moderate inhibitors: 
aprepitant 
erythromycin 
diltiazem
fluconazole 
grapefruit juice 
Seville orange juice 
verapamil
Weak inhibitors:
cimetidine
All other inhibitors:
amiodarone
NOT azithromycin 
chloramphenicol 
boceprevir 
ciprofloxacin 
delaviridine
diethyl-dithiocarbamate 
fluvoxamine
gestodene 
imatinib 
mibefradil
mifepristone 
norfloxacin
norfluoxetine 
star fruit 
telaprevir 
troleandomycin
voriconazole
Carbamazepine
Efavirenz 
Nevirapine 
Barbiturates 
Glucocorticoids 
Modafinil 
Oxcarbarzepine 
Phenobarbital 
Phenytoin 
Pioglitazone 
Rifabutin 
Rifampin
St. John’s Wort 
Troglitazone
Source: 
http://medicine.iupui.edu/clinpharm/ddis/table.aspx.

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17.3 APPENDIX C: ELECTROLYTE IMBALANCES MANAGEMENT AND TUMOR LYSIS SYNDROME 
PREVENTION
NOTE: The following are recommendations for initial management of electrolyte 
imbalances and prevention of Tumor Lysis Syndrome (TLS).
First Dose of Venetoclax or Dose Increase
•
Within the first 24 hours after either the first dose or dose increase, if any 
laboratory criteria below are met, the participant should be hospitalized for 
monitoring and the investigator notified. No additional venetoclax doses should be 
administered until resolution. A rapidly rising serum potassium level is a medical 
emergency.
o
If resolution of TLS occurs within 24-48 hours, venetoclax may be 
resumed at the same dose.
o
If TLS persists for >48 hours, venetoclax should be restarted at a 
lower starting dose.
o
In participants who meet criteria for clinical TLS, venetoclax should 
be restarted at a lower dose following TLS resolution.
•
Nephrology (or acute dialysis service) should be consulted/contacted on admission 
(per institutional standards to ensure emergency dialysis is available).
•
IV fluids (e.g., D5 1/2 normal saline) should be initiated at a rate of at least 1 mL/kg/h 
rounded to the nearest 10 mL (target 150 to 200 mL/h; not  50 mL/h). 
Modification of fluid rate should also be considered for individuals with specific 
medical needs.
•
Monitor for symptoms or signs of TLS (e.g., fever, chills, tachycardia, nausea, 
vomiting, diarrhea, diaphoresis, hypotension, muscle aches, weakness, 
paresthesias, mental status changes, confusion, and seizures). If any clinical 
features are observed, recheck potassium, phosphorus, uric acid, calcium, and 
creatinine within 1 hour.
•
Vital signs should be taken at time of all blood draws or any intervention.
•
The management recommendations below focus on the minimum initial responses 
required. If a diagnosis of TLS is established, ongoing intensive monitoring and 
multi-disciplinary management will be per institutional protocols.

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Table 10:Management of Electrolyte Imbalances
Abnormality
Management Recommendations
Hyperkalemia (including rapidly rising potassium)
Potassium  0.5 mmol/L 
increase from prior value 
(even if potassium within 
normal limits [WNL])
• Recheck potassium, phosphorus, uric acid, calcium, and 
creatinine in 1 hour. If further  0.2 mmol/L increase in 
potassium, but still  upper limit of normal (ULN), manage per 
potassium  ULN. Otherwise recheck in 1 hour.
• Resume per protocol testing if change in potassium
is  0.2 mmol/L, and potassium  ULN, and no other evidence of 
tumor lysis.
• At discretion of investigator, may recheck prior to 
hospitalization. If stable or decreased, and still WNL, 
hospitalization is at the discretion of the investigator. Potassium, 
phosphorus, uric acid, calcium, and creatinine must be rechecked 
within 24 hours.
Potassium  upper limit 
of normal
• Perform immediate ECG and commence telemetry.
• Nephrology notification with consideration of initiating dialysis
• Administer Kayexalate 60 g (or Resonium A 60 g).
• Administer furosemide 20 mg IV  1.
• Administer calcium gluconate 100 to 200 mg/kg IV slowly if 
there is ECG/telemetry evidence of life-threatening arrhythmias.
• Recheck potassium, phosphorus, uric acid, calcium, and 
creatinine in 1 hour.
• If potassium  ULN 1 hour later, repeat potassium, phosphorus, 
uric acid, calcium, and creatinine 1, 2, and 4 hours later, if no 
other evidence of tumor lysis.
Potassium  6.0 mmol/L 
(6.0 mEq/L) and/or 
symptomatic
(e.g., muscle cramps, 
weakness, paresthesias, 
nausea, vomiting, 
diarrhea)
• Perform immediate ECG and commence telemetry.
• Nephrology assessment with consideration of initiating dialysis
• Administer Kayexalate 60 g (or Resonium A 60 g).
• Administer furosemide 20 mg IV  1.
• Administer insulin 0.1 U/kg IV  D25 2 mL/kg IV.
• Administer sodium bicarbonate 1 to 2 mEq/kg IV push.
- If sodium bicarbonate is used, rasburicase should not be used 
as this may exacerbate calcium phosphate precipitation.
• Administer calcium gluconate 100 to 200 mg/kg IV slowly if 
there is ECG/telemetry evidence of life-threatening arrhythmias. 
Do not administer in same IV line as sodium bicarbonate.
• Recheck potassium, phosphorus, uric acid, calcium, and 
creatinine every hour.
Hyperuricemia

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Abnormality
Management Recommendations
Uric acid  8.0 mg/dL 
(476 mol/L)
• Consider rasburicase (dose per institutional guidelines).
- If rasburicase is used, sodium bicarbonate should not be used 
as this may exacerbate calcium phosphate precipitation.
• Recheck potassium, phosphorus, uric acid, calcium, and 
creatinine in 1 hour.
Uric acid  10 mg/dL 
(595 µmol/L)
OR
Uric acid  8.0 mg/dL 
(476 µmol/L) with 25% 
increase and creatinine 
increase  0.3 mg/dL 
( 0.027 mmol/L) from 
pre-dose level
• Administer rasburicase (dose per institutional guidelines).
- If rasburicase is used, sodium bicarbonate should not be used 
as this may exacerbate calcium phosphate precipitation.
• Consult nephrology.
• Recheck potassium, phosphorus, uric acid, calcium, 
and creatinine in 1 hour.
• If uric acid  8.0 mg/dL 1 hour later, repeat potassium, 
phosphorus, uric acid, calcium, and creatinine 2 and 4 hours 
later, if no other evidence of tumor lysis.
Hypocalcemia
Corrected calcium
 7.0 mg/dL
(1.75 mmol/L) 
AND
Participant 
symptomatic (e.g., 
muscle cramps, 
hypotension, tetany, 
cardiac arrhythmias) in 
the presence of 
hypocalcemia
• Administer calcium gluconate 50 to 100 mg/kg IV slowly with 
ECG monitoring.
• Telemetry.
• Recheck potassium, phosphorus, uric acid, calcium, and 
creatinine in 1 hour.
• If calcium normalized 1 hour later, repeat potassium, 
phosphorus, uric acid, calcium, and creatinine 2 and 4 hours 
later, if no other evidence of tumor lysis.
• Calculate corrected calcium and ionized calcium if albumin is 
low.
Hyperphosphatemia
Phosphorus  5.0 mg/dL 
(1.615 mmol/L) with
 0.5 mg/dL
(0.16 mmol/L) increase
• Administer a phosphate binder (e.g., aluminum hydroxide, 
calcium carbonate, sevelamer hydroxide, or lanthanum 
carbonate).
• Nephrology notification (dialysis required for phosphorus
 10 mg/dL)
• Recheck potassium, phosphorus, uric acid, calcium, and 
creatinine in 1 hour.
• If phosphorus  5.0 mg/dL 1 hour later, repeat potassium, 
phosphorus, uric acid, calcium, and creatinine 2 and 4 hours 
later, if no other evidence of tumor lysis.
Creatinine
Increase  25% from 
baseline
• Start or increase rate of IV fluids.
• Recheck potassium, phosphorus, uric acid, calcium, and 
creatinine in 1 to 2 hours.

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Ongoing Dosing of Venetoclax
Management of electrolyte changes from last value at intervals  24 hours after either 
the first dose or dose increase (e.g., 48 or 72 hours) are as below. NOTE: If the 
participant is hospitalized, no additional venetoclax doses should be administered until 
resolution.
•
For potassium, admit participant for any increase  1.0 mmol/L (1.0 mEq/L), or any 
level  upper limit of normal.
Refer to the management guidelines for electrolyte changes observed 
within the first 24 hours after either the first dose or dose increase (Table 
10)
•
If a smaller potassium increase is observed that does not meet the criteria for 
admission above, recheck potassium, phosphorus, uric acid, calcium, and creatinine 
in 24 hours and confirm no evidence of TLS prior to further venetoclax dosing.
•
For uric acid, calcium, phosphorus, and creatinine, refer to the management 
guidelines for electrolyte changes observed within the first 24 hours after either 
the first dose or dose increase (Table 10).

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17.4 APPENDIX D: LUGANO CLASSIFICATION CRITERIA

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17.5 APPENDIX E: STUDY DRUG DIARY
Participant ID:  
Cycle:  
Instructions:
•
Use this diary to record all doses of oral study medication taken.  
•
You should bring this study drug diary and each of your study medications (including 
leftover pills and empty bottles) with you to each clinic visit. 
•
Contact us if you have any side effects or before starting any new medications or over-the-
counter drugs.
•
If you have questions at any time, please contact your doctor or nurse.
Study Drugs:
The study medications should be taken as follows, the dose of each will be assigned to you by your 
doctor:  
V = Venetoclax
Venetoclax tablets should be taken with a glass of water and food
VI =VIP152
VIP152 is given by IV, in the clinic
P = Prednisone
Prednisone tablets should be taken with a glass of water with or without food
NOTE:  All oral study medications may be taken together; with food on days 
when taken together.
Additional Information:
•
Each of the study drugs should be taken at about the same time each day, with or without 
food as described above (see example below).  
•
If you do not remember to take all or any of the medications on any day, please tell us.  
Do not make-up the dose or take extra the following day to make-up for the missed dose.
•
If you vomit after taking a dose, you should not take another dose that day.  
STAFF USE ONLY
Date returned/reviewed:  
Staff member:  
Notes/Comments:

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Study Drug Diary:
These are examples of how you might take the study drugs:
•
Day -1: Please drink 2 to 3 liters (e.g., 4 to 6, 16 oz. bottles) of water at home.
•
Day 1: Take the venetoclax and prednisone with water when instructed, with or without food. 
•
Day 2:  In clinic, take the venetoclax and prednisone with water and food when instructed. About 
30-60 minutes later, receive the VIP152 infusion.  
•
Days 3 through 8:  Take the venetoclax and  prednisone with water and food (e.g., with 
breakfast).  
•
Day 9: In clinic, take the venetoclax and prednisone with water and food when instructed. About 
30-60 minutes later, receive the VIP152 infusion.
•
Day 10:  Take the venetoclax and prednisone with water and food (e.g., with breakfast).
•
Days 12-21:  No study drugs are taken on these days.  
Please record the dose/number of pills of each study drug taken in the table below:
Study Drugs
Venetoclax
Prednisone
VIP152
Pegfilgrastim 
Cycle 
Day
Date
V
P
VI
Comments
-1
NO DRUG
Fluid Intake
1
NONE
NONE
2
IV in clinic
NONE
3
NONE
NONE
4
NONE
NONE
5
NONE
NONE
6
NONE
NONE
7
NONE
NONE
8
NONE
NONE
9
IV in clinic
NONE
10
NONE
NONE
11
NONE
NONE
NONE
12-21
NO DRUG