Clinical trial NCT04478123
Conditions: Multiple Myeloma Hodgkin Lymphoma Non-Hodgkin Lymphoma HDT-AHCT
Keywords: High-Dose Therapy Autologous Hematopoietic Cell Transplantation Romiplostim Thrombocytopenia 20-180
Sponsor: Memorial Sloan Kettering Cancer Center
Start date: 2020-07-14; Completion date: 2023-06-08
Enrollment: 62 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to see if the study drug, romiplostim, helps low platelet count caused by the standard blood cancer treatment of chemotherapy and autologous hematopoietic cell transplantation. This study will also look at whether romiplostim can decrease the number of times the participant needs to return to the clinic for platelet transfusions to treat their low platelet count. In addition, the researchers will determine how safe it is to give romiplostim to people with blood cancer who have received treatment with chemotherapy and autologous hematopoietic cell transplantation.

Detailed description:

Arms: arm 1: Patients will be enrolled prior to admission for High-Dose Therapy and Autologous Hematopoietic Cell Transplantation (HDT-AHCT), and they will undergo their planned HDT-AHCT for their respective hematologic malignancy as per institutional standards.

Regardless of the conditioning regimen received, all patients will receive romiplostim 3.0 mcg/kg SC on Day +1 and romiplostim 2.0 mcg/kg SC on Day +8 after HDT-AHCT. Beyond Day +8, patients will be treated until platelet count is \>50,000/mcL, without any platelet transfusions in the prior 48 hours. All doses after the second romiplostim dose will be titrated as per Table 3, based on weekly CBC/platelet counts. No patient will receive more than six doses of romiplostim, even if platelets have not corrected by Day +42.
Interventions: intervention 1: Romiplostim
Intervention descriptions: intervention 1: Romiplostim 3.0 mcg/kg SC on Day +1 and Romiplostim 2.0 mcg/kg SC on Day +8 after HDT-AHCT. Beyond Day +8, patients will be treated weekly until platelet count is \>50,000/mcL, without any platelet transfusions in the prior 48 hours. All doses after the second Romiplostim dose will be titrated as per Table 3, based on weekly CBC/platelet counts. Patients will receive a maximum of six weekly doses of romiplostim.

Protocol documents:
Prot_SAP_000.pdf: 
Memorial Sloan Kettering Cancer Center 
IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
 
 
 
 
 
MSK PROTOCOL COVER SHEET 
An Open-Label, Pilot Study of Romiplostim for Conditioning Regimen-Related 
Thrombocytopenia after High-Dose Therapyand Autologous Hematopoietic Cell 
Transplantation 
 
Principal Investigator/Department: Dr. Michael Scordo/Medicine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Memorial  Sloan Kettering Cancer Center 
1275 York Avenue  
New York, New York 10065 
 
 
 
 
Page 1 of 24 


Memorial Sloan Kettering Cancer Center 
IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
Memorial  Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 2 of 24 
 
 
 
Table of Contents 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA........................................................................... 3 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS.................................................................................... 3 
3.0 
BACKGROUND AND RATIONALE ......................................................................................... 3 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION ........................................................................ 4 
4.1 
Design ...................................................................................................................................... 6 
4.2 
Intervention ..................................................................................................................................... 6 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS & NON-THERAPEUTIC ASSESSMENTS ................ 7 
6.0 
CRITERIA FOR PARTICIPANT ELIGIBILITY .......................................................................... 9 
6.1 
Participant Inclusion Criteria ..................................................................................................... 9 
6.2 
Participant Exclusion Criteria .................................................................................................... 9 
7.0 
RECRUITMENT PLAN .......................................................................................................................... 9 
7.1 
Research Participant Registration .......................................................................................... 10 
7.2 
Randomization ....................................................................................................................... 10 
8.0 
INFORMED CONSENT PROCEDURES ........................................................................................ 10 
9.0 
PRE-TREATMENT/INTERVENTION ..................................................................................... 11 
10.0 
TREATMENT/INTERVENTION PLAN ................................................................................... 11 
11.0 
EVALUATION DURING TREATMENT/INTERVENTION ........................................................ 12 
12.0 
CRITERIA FOR REMOVAL FROM STUDY ........................................................................... 13 
13.0 
CRITERIA FOR OUTCOME ASSESSMENT AND ENDPOINT EVALUABILITY .................... 14 
14.0 
BIOSTATISTICS ................................................................................................................... 14 
15.0 
TOXICITIES/RISKS/SIDE EFFECTS ............................................................................................ 14 
15.1 
Serious Adverse Event (SAE) Reporting .................................................................................... 16 
15.2. External SAE Reporting ............................................................................................................ 17 
16.0 
PROTECTION OF HUMAN PARTICIPANTS ......................................................................... 18 
16.1 
Privacy ................................................................................................................................... 18 
16.2 
Data Management .................................................................................................................... 18 
16.3 
Quality Assurance .................................................................................................................. 19 
16.4 
Data and Safety Monitoring ......................................................................................................... 19 
17.0 
REFERENCES ..................................................................................................................... 20 
18.0 
APPENDICES ....................................................................................................................... 21 
19.0 
MSK MULTICENTER TRIAL ADDENDUM………………………………………………………22 


Memorial Sloan Kettering Cancer Center 
IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
Memorial  Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 3 of 24 
 
 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
 
 
 
 
 
 
 
 
 
2.1 
OBJECTIVES AND SCIENTIFIC AIMS 
 
Primary Objective 
 
1) To evaluate whether receiving romiplostim after HDT-AHCT decreases the number of 
days requiring platelet transfusions or grade 4 CTCAE thrombocytopenia following HDT- 
AHCT 
 
Secondary Objectives 
INTERVENTION 
• 
Romiplostim 3.0 mcg/kg SC on Day +1 and Romiplostim 2.0 mcg/kg 
SC on Day +8 after HDT-AHCT. Beyond Day +8, patients will be 
treated weekly until platelet count is >50,000/mcL, without any platelet 
transfusions in the prior 48 hours. All doses after the second 
Romiplostim dose will be titrated as per Table 3, based on weekly 
CBC/platelet counts. Patients will receive a maximum of six weekly 
doses of romiplostim. 
➢ Romiplostim doses after Day +8 may have a +2 day window 
• 
Lab assessments: 
➢ CBC, CMP, and Immature Platelet Fraction every day from day 
of AHCT (Day 0) until Day +15. All patients will get at least 
weekly (+/- 3 days) labs until day +30. Patients who need 3 or 
more doses of romiplostim will get weekly (+/- 3 days) labs as 
long as their platelet count is ≥25,000. For patients who need 3 
or more doses of romiplostim they will receive labs every 
second day until their platelets are ≥25,000. 
➢ LDH, PT/INR, APTT every 7 days (+/-2 days) from Day +1 until 
Day +15. 
➢ CBC, CMP, Immature Platelet Fraction, LDH, PT/INR, and 
APTT will be done at days +30 (+/- 7 days), +60 (+/- 7 days) 
and at +100 (+/- 14 days) from AHCT. 
TARGET PATIENTS 
Adult patients ≥ 18 years old undergoing high-dose therapy and autologous 
hematopoietic cell transplantation (HDT-AHCT) for : Multiple  myeloma (MM),  Hodgkin 
lymphoma (HL) or non-Hodgkin  lymphoma (NHL). 


Memorial Sloan Kettering Cancer Center 
IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
Memorial  Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 4 of 24 
 
 
 
1) To evaluate whether romiplostim can reduce the number of platelet transfusions issued 
during the AHCT admission 
 
2) To evaluate whether romiplostim can reduce the time to platelet engraftment after HDT- 
AHCT Platelet engraftment is defined as the first day of seven consecutive days with a 
platelet count of ≥20 K/mcL without transfusion support. 
 
3) To evaluate whether romiplostim can reduce the length of stay of AHCT 
 
4) The safety profile of romiplostim will be assessed in this patient population during the 
course of the study as per Section 11.0 Toxicities/Side Effects. 
 
3.0 
BACKGROUND AND RATIONALE 
 
HDT-AHCT and Chemotherapy-Induced Thrombocytopenia (CIT) 
 
High-dose therapy and autologous hematopoietic cell transplantation (HDT-AHCT) remains a 
standard of care consolidation strategy for patients with multiple myeloma (MM)  that provides 
prolonged disease-free survival.1,2  The standard conditioning regimen for MM is  
monotherapy with high-dose melphalan.2  HDT-AHCT is also a potentially curative modality  
for patients with relapsed, chemosensitive Hodgkin lymphoma (HL) and non-Hodgkin 
lymphoma (NHL).3,4  For HL and the majority of NHL subtypes, the most commonly used 
conditioning regimen is BEAM [carmustine, etoposide, cytarabine, and melphalan] followed 
by CBV [cyclophosphamide, carmustine, and etoposide].4–6   In recent years, for patients with 
central nervous system lymphoma (CNSL), our group and others have successfully utilized 
an intensive conditioning regimen, TBC [thiotepa, busulfan, and cyclophosphamide.]7–9 
The HDT-AHCT platform is built upon myeloablative conditioning, which consists of single 
agent or combination chemotherapies aimed at overcoming potential residual disease and 
any possible chemoresistance.4 In doing so, the normal hematopoietic cell compartment of 
the bone marrow is also eliminated, after which an infusion of autologous stem cells is 
required to restore normal hematopoiesis roughly 2 weeks after AHCT. There are profound 
cytopenias following AHCT prior to engraftment, notably thrombocytopenia. Currently, the 
management of chemotherapy-induced thrombocytopenia (CIT) is supportive with platelet 
transfusions per the discretion of the treating medical oncologist.10  Most patients undergoing 
HDT-AHCT require multiple platelet transfusions during their AHCT hospitalization. Platelet 
transfusions are generally given to non-bleeding patients with severe  thrombocytopenia. For 
inpatient stem cell transplantations, the standard platelet transfusion threshold is to transfuse 
if platelets are < 10,000/mcL. For outpatient stem cell transplantations, the standard platelet 
transfusion threshold is to transfuse if platelets are < 20,000/mcL. Patients may also be 
transfused for any platelet count if necessary for clinical reasons, if deemed appropriate by 
the treating physician. Even after neutrophil engraftment, thrombocytopenia often delays 
hospital discharge and increases the risk of bleeding complications.11,12 Table 1 presents the 
MSKCC historic thrombocytopenia data in patients undergoing HDT-AHCT from 2014 
through 2016. The key parameters presented are platelet transfusions issued (mean, 
median, range), day to platelet engraftment, day to neutrophil engraftment, and length of 
stay. Neutrophil engraftment after transplantation is defined as an absolute neutrophil count 


Memorial Sloan Kettering Cancer Center 
IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
Memorial  Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 5 of 24 
 
 
 
(ANC) ≥ 500 K/mcL for 3 consecutive days. The first of these 3 consecutive days is 
considered the day of neutrophil engraftment. Platelet engraftment is defined as the time 
after transplantation needed to achieve a platelet count exceeding 20,000/mcL without 
transfusion support for 7 consecutive days. The first of those 7 consecutive days is 
considered the day of platelet engraftment. 
 
 
Table 1. Historical Data on Platelet Transfusions (Based on MSKCC experience from 2017 through 
2020) 
 
Cohort 
No. of 
Patients 
Median No. 
Platelets 
Issued Per 
Patient 
(Range) 
Mean No. 
Platelets 
Issued 
Per 
Patient 
(IQR) 
Median No. days 
with Transfusions or 
Grade 4 
Thrombocytopenia 
(Range) 
Mean No. days with 
Transfusions or Grade 
4 Thrombocytopenia 
(IQR) 
MM 
Melphalan 
485 
2 (0-19) 
2.65 (1-3) 
5 (0-53) 
6.8 (3-8) 
NHL and HL 
296 
4 (0-44) 
5 (3-6) 
8 (2-68) 
9.5 (6-10) 
BEAM/CBV 
TBC 
73 
5 (2-32) 
6.3 (4-7) 
10 (5-38) 
11.9 (8-13) 
 
MM: multiple myeloma; NHL: non-Hodgkin lymphoma; HL: Hodgkin lymphoma; BEAM: carmustine, 
etoposide, cytarabine, and melphalan; CBV: cyclophosphamide, carmustine, and etoposide; TBC: 
thiotepa, busulfan, and cyclophosphamide. 
 
 
Romiplostim – Mechanism of Action and Clinical Activity 
 
Romiplostim (Nplate®) is a thrombopoietin (TPO) mimetic that binds to the TPO receptor 
(Mpl).13  It is a ‘peptibody’ formed by the fusion of the Fc portion of an IgG1 monoclonal 
antibody with four TPO mimetic peptides. It binds the distal cytokine homology region of the 
TPO receptor leading to the activation of the JAK/STAT pathyway.14  In addition, it has been 
shown to activate the MAP kinase pathway leading to activation of anti-apoptotic pathways 
resulting in increased platelet production. Romiplostim is FDA approved for use in chronic 
immune thrombocytopenia (ITP), and it has been shown to increase and maintain platelet 
counts in splenectomized and non-splenectomized patients with few adverse effects.15,16 To 
date, no anti-TPO antibody formation of clinical significance has been reported. In several 
trials of patients with ITP, the mean therapeutic dose of romiplostim to achieve a platelet 
count of 50-200,000/mcL was 3-4 mcg/kg.10,14 
At MSKCC, our Hematology Service has extensive experience using romiplostim for 
chemotherapy-induced thrombocytopenia (CIT), in patients with advanced stage solid tumor 
malignancies.18  The goal of romiplostim therapy was improvement and maintenance of 
platelet counts to >100,000/mcL in order to allow for the resumption and continuation of 
cancer-directed therapy. The results of an investigator-initiated, phase II,  open-label clinical 


Memorial Sloan Kettering Cancer Center 
IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
Memorial  Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 6 of 24 
 
 
 
trial of romiplostim for CIT in patients with advanced stage solid tumors versus observation 
control were recently reported.19   The observation-control patients who did not correct their 
platelet counts were eligible to crossover to the romiplostim arm. A total of 40 patients were 
enrolled, with 32 patients receiving up-front romiplostim and 8 observation patients.  27 of the 
32 (84%) of the romiplostim-treated patients corrected their platelets to target goal within 3 
weeks. After correction of their platelet count, 25 of these patients resumed chemotherapy, 
and all but one were able to maintain their scheduled chemotherapy treatments without 
recurrence of CIT.  The mean effective romiplostim dose was 2.5 mcg/kg (range 1.8-4.1). 
Importantly, there were no observed adverse effects on the bone marrow.  Four patients 
(12.5%) of the 32 treated patients had a non-fatal thrombotic event. It is important to note 
that all of these patients were at high risk of thrombosis based on their underlying 
malignancy, and this incidence of thrombosis is considered within a typical range in patients 
with advanced solid tumors on chemotheray.19 
An unmet need exists for an alternative to platelet transfusions for patients undergoing HDT- 
AHCT. Blood product transfusions are costly and there are risks of short-term and long-term 
transfusion complications.  Further, responses to platelet transfusions are short-lived, 
typically 12 hours or less.  Enhancing platelet engraftment with romiplostim, post HDT-AHCT 
would be a highly attractive. 
 
 
4.1 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
 
4.2 
Design 
 
We are proposing a single-center, open-label, pilot study of romiplostim for patients 
undergoing HDT-AHCT. We will enroll a total of 63 patients within 18 months of opening of 
the study to reach a sample size of 60 patients. Patients will have (A) MM undergoing high- 
dose melphalan and AHCT, (B) HL or NHL undergoing BEAM- or CBV-AHCT or (C) CNSL 
undergoing  TBC-AHCT. 
 
Further: 
 
• 
At least 20 will have MM undergoing high-dose melphalan and AHCT 
• 
At least 20 will have HL or NHL undergoing BEAM- or CBV-AHCT. 
• 
Remaining patients with MM or HL/NHL as available to reach final sample size of 60 
patients 
Patients will be enrolled prior to admission for HDT-AHCT, and they will undergo their 
planned HDT-AHCT for their respective hematologic malignancy as per institutional 
standards as follows: 
We hypothesize that the use of romiplostim after HDT-AHCT will: (A) Reduce the number of 
days requiring platelet transfusions or grade 4 CTCAE thrombocytopenia following HDT- 
AHCT; (B) Reduce the number of platelet transfusions issued during the AHCT admission; 


Memorial Sloan Kettering Cancer Center 
IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
Memorial  Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 7 of 24 
 
 
 
(C) Reduce the time to platelet engraftment after AHCT; (D) Reduce the length of stay for the 
AHCT as compared to historical data. 
4.3 
Intervention 
 
Patients will be enrolled prior to admission for HDT-AHCT, and they will undergo their 
planned HDT-AHCT for their respective hematologic malignancy as per institutional 
standards as detailed in Section 9.0 Treatment/Intervention Plan. 
Regardless of the conditioning regimen received, all patients will receive romiplostim 3.0 
mcg/kg SC on Day +1 and romiplostim 2.0 mcg/kg SC on Day +8 after HDT-AHCT. Beyond 
Day +8, patients will be treated until platelet count is >50,000/mcL, without any platelet 
transfusions in the prior 48 hours. All doses after the second romiplostim dose will be titrated 
as per Table 3, based on weekly CBC/platelet counts. No patient will receive more than six 
doses of romiplostim, even if platelets have not corrected by Day +42. 
If there is a medical circumstance wherein the platelets decrease to <20,000/mcL, 
romiplostim can be resumed during hospitalization at the discretion of the treating physician 
for medical necessity. Throughout the study, all patients will receive weekly doses of 
romiplostim. 
Table 3. Individualized Treatment Dose Adjustment by Platelet Count for 3rd  – 6th Romiplostim 
Doses 
 
Platelet Count 
Romiplostim Dose 
PLT < 20,000 mcL 
3.0 mcg/kg 
20,000 ≤ PLT ≤ 35,000 mcL 
2.0 mcg/kg 
35,000 < PLT ≤ 50,000 mcL 
1.0 mcg/kg 
 
 
5.1 
THERAPEUTIC/DIAGNOSTIC AGENTS & NON-THERAPEUTIC ASSESSMENTS 
 
Romiplostim, a TPO mimetic, is an Fc-peptide fusion protein (peptibody) that activates 
intracellular transcriptional pathways leading to increased platelet production via the TPO 
receptor (known as cMpl). The peptibody molecule contains two identical single-chain 
subunits, each consisting of human immunoglobulin IgG1 Fc domain, covalently linked at the 
C-terminus to a peptide containing two thrombopoietin receptor-binding domains. 
Romiplostim has no amino acid sequence homology to endogenous TPO. Romiplostim is 
produced by recombinant DNA technology in Escherichia coli (E coli).14,15 
Romiplostim is approximately 59 kilodalton and is comprised of 4 Mpl-binding domains and 
an Fc fragment. The peptibody is produced by recombinant DNA technology in Escherichia 
coli (E coli). Though it has no amino acid sequence homology to endogenous thrombopoietin 
(eTPO), romiplostim is an agonist of the thrombopoietin (TPO) receptor and signals and 
activates intracellular transcriptional pathways to increase platelet production. 
Romiplostim is supplied as a sterile, preservative-free lyophilized white powder ready for 
reconstitution. It is supplied for single use in 5 cc Type I glass vials containing 625 μg of 


Memorial Sloan Kettering Cancer Center 
IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
Memorial  Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 8 of 24 
 
 
 
romiplostim, 500 μg deliverable drug product. When reconstituted with the appropriate 
volume of sWFI, romiplostim is at a concentration of 0.5 mg/mL in 10 mM histidine, 4% (w/v) 
mannitol, 2% (w/v) sucrose, and 0.004% (w/v) polysorbate 20 at a pH of 5.0. The product, 
when reconstituted, is a clear colorless solution practically free from particles. 
Prior to administration, romiplostim is reconstituted in the vial to 0.5 mg/mL (1.2 ml of sWFI is 
added to vials containing 625 μg (500 μg) of romiplostim), and drawn into a syringe for 
subcutaneous injection. 
Romiplostim vials will be stored in their carton to protect from light until the time of use.  Keep 
romiplostim vials refrigerated at 2°to 8°C (36° to 46°F).  Do not freeze. 
A. Romiplostim is an FDA approved drug, approved for the indication of chronic immune 
(idiopathic) thrombocytopenic purpura (ITP). The investigators brochure, provided by 
Amgen, is attached as Appendix A. 
B. Relevant statements from the Product Insert: 
 
1. INDICATIONS  AND USAGE: “Romiplostim is a thrombopoietin receptor agonist 
indicated for the treatment of thrombocytopenia in patients with chronic immune 
thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, 
immunoglobulins, or splenectomy.” 
• 
Active Ingredients:  Romiplostim 
• 
Pharmacological Class: Thrombopoietin receptor agonist 
• 
Structural Formula: 
 
 
• 
Dose Formulation: Romiplostim is supplied in a 5-mL single-use vial as a sterile, 
white, preservative-free, lyophilized powder containing a protein concentration of 0.5 


Memorial Sloan Kettering Cancer Center 
IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
Memorial  Sloan Kettering Cancer Center 
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New York, New York 10065 
Page 9 of 24 
 
 
 
mg/mL of 10 mM histidine, 4.0% mannitol, 2.0% sucrose, 0.004% polysorbate 20, 
and a pH 5.0 when reconstituted with 1.2 mL of sterile water for injection. 
• 
Storage: Lyophilized product should be stored refrigerated at 2°C to 8°C (36°F to 
46°F); vials should be kept in the carton to protect from light until time of use. Do not 
freeze. Alternatively,  the romiplostim lyophilized product can be kept at room 
temperature up to 25°C (77°F) in the original carton; however, under these 
conditions, the romiplostim lyophilized product must be used within 30 days. If not 
used within 30 days, discard romiplostim. Protect romiplostim from direct light and do 
not expose to temperatures above 25°C (77°F). 
• 
Source of Supply: Drug will be supplied by Amgen Inc. 
 
6.1 
CRITERIA FOR PARTICIPANT ELIGIBILITY 
 
6.2 
Participant Inclusion Criteria 
 
1. Adult patients ≥ 18 years old diagnosed with multiple myeloma (MM), any subtype of 
Hodgkin lymphoma (HL), or any subtype of non-Hodgkin lymphoma (NHL). 
o For MM,  the conditioning regimen used will be high-dose melphalan. 
o For HL and NHL, the conditioning will be one of the following high-dose 
regimens: BEAM, CBV, or TBC. 
o Other conditioning regimens not listed above, or variations of the above 
conditioning regimens, may be allowed at the discretion of the principal 
investigator if the regimen is considered myeloablative. 
2. Adequate organ function is required, defined as follows: 
o Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia. 
o AST, ALT, and alkaline phosphatase < 3 times the upper limit of normal. 
o Creatinine clearance ≥ 40 ml/min (calculated by Cockcroft Gault) 
o LVEF ≥ 45% by MUGA or resting echocardiogram. 
o Pulmonary function (FEV1 and corrected DLCO) ≥ 45% predicted. 
o Adequate performance status ECOG ≤ 2. 
3. Ability to provide written informed consent. 
4. Patients undergoing  HDT-AHCT. 
 
6.3 
Participant Exclusion Criteria 
 
1. Patients with a previous diagnosis of a myeloid malignancy. 
2. Patients for whom the treating oncologist will be using a non-standard platelet 
transfusion threshold during the AHCT. 
3. Patients with a history of a prior symptomatic or incidental venous thromboembolic 
event (such as DVT or pulmonary embolism) within the prior 6 months are eligible if 
they are on and tolerating anti-coagulation, or greater than 6 months ago are eligible 
if they completed or are on and tolerating anti-coagulation. 
o A venous thrombotic event associated with a central venous catheter will not 
make the patient ineligible. 


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IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
Memorial  Sloan Kettering Cancer Center 
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New York, New York 10065 
Page 10 of 24 
 
 
 
4. Patients with a history of symptomatic arterial thrombotic events such as myocardial 
infarction, ischemic cerebral vascular accident or transient ischemic attack in the past 
6 months are ineligible. 
5. Patients who had been diagnosed with Immune Thrombocytopenic Purpura (ITP) at 
any time prior to the AHCT are ineligible. 
6. Patients with a serious concomitant medical condition that could interfere with the 
conduct of the clinical trial, such as unstable angina, renal failure requiring 
hemodialysis, or active infection requiring IV antibiotics. 
7. Previous use of romiplostim, PEGylated recombinant human megakaryocyte growth 
and development factor, eltrombopag, recombinant human TPO, any other TPO 
receptor agonist, or any investigational platelet producing agent. 
8. Females who are pregnant or breastfeeding or planning to become pregnant or 
breastfeed during treatment and for an additional 30 days after treatment 
discontinuation or longer if required by prescribing information for chemotherapy 
received during the study. 
9. Patients unwilling to use highly effective contraception during the study period and for 
the duration required by prescribing information for chemotherapy(ies) administered 
during the study. 
7.0 
RECRUITMENT PLAN 
 
This study will be conducted at MSKCC. Potential research subjects will be identified by 
members of the Adult Bone Marrow Transplant (BMT) and Hematology Services. After 
consultation with the Adult BMT attending physician, eligible patients will be asked to 
participate in the study. If consent is offered, the risks and benefits will be presented to the 
patient by an investigator prior to the patient consenting. If the patient consents, they will be 
enrolled/registered by a clinical research coordinator. 
 
This study does not compete with any existing or planned other studies for conditioning- 
regimen induced thrombocytopenia, and therefore, we anticipate a high percent of the 
appropriate patients who are undergoing HDT-AHCT will be referred and enrolled. 
 
7.1 
Research Participant Registration 
 
Confirm eligibility as defined in the section entitled Inclusion/Exclusion Criteria. Obtain 
informed consent, by following procedures defined in section entitled Informed Consent 
Procedures. During the registration process registering individuals will be required to 
complete a protocol specific Eligibility Checklist. The individual  signing the Eligibility Checklist 
is confirming whether the participant is eligible to enroll in the study. Study staff are 
responsible for ensuring that all institutional requirements necessary to enroll a participant to 
the study have been completed. See related Clinical Research Policy and Procedure #401 
(Protocol Participant Registration). 
 
7.2 
Randomization 
 
There will be no randomization in this study. 
 
8.1 
INFORMED CONSENT PROCEDURES 


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IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
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Page 11 of 24 
 
 
 
Before protocol-specified procedures are carried out, consenting professionals will explain  
full details of the protocol and study procedures as well as the risks involved to participants 
prior to their inclusion in the study. Participants will also be informed that they are free to 
withdraw from the study at any time. All participants must sign an IRB/PB-approved consent 
form indicating their consent to participate. This consent form meets the requirements of the 
Code of Federal Regulations and the Institutional Review Board/Privacy Board of this Center. 
The consent form will include the following: 
1. The nature and objectives, potential risks and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of supportive 
care for therapeutic studies.) 
4. The name of the investigator(s) responsible for the protocol. 
5. The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time. 
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information.  In 
addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
 
9.1 
PRE-TREATMENT/INTERVENTION 
 
Documentation of tests resulted and/or verification will be completed within the following 
guidelines before enrolling on trial: 
 
W ithin 28 days prior to enrollment: 
• 
Complete Blood Count (CBC) with differential. 
• 
Comprehensive Metabolic Panel (CMP) (must include: BUN, Creatinine, sodium, 
potassium, chloride, CO2, calcium, glucose, total Bilirubin, total protein, albumin, 
alkaline phosphatase, AST, ALT) 
• 
Lactate Dehyrogenase (LDH) 
• 
Prothrombin Time (PT), International  Normalized Ratio (INR) 
• 
Activated Partial Thromboplastin Time (APTT) 
• 
If patients have not had prior cytogenetic testing with FISH panel for MDS from a 
bone marrow aspirate and/or biopsy or peripheral blood testing, this will be performed 
during screening. 
• 
Pulmonary Function Test 
• 
MUGA or resting echocardiogram 
W ithin 48 hours of enrollment, 
• 
Complete Blood Count (CBC) with differential. 


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• 
Comprehensive Metabolic Panel (CMP) (must include: BUN, Creatinine, sodium, 
potassium, chloride, CO2, calcium, glucose, total Bilirubin, total protein, albumin, 
alkaline phosphatase, AST, ALT) 
• 
Lactate Dehyrogenase (LDH) 
• 
Prothrombin Time (PT), International  Normalized Ratio (INR) 
• 
Activated Partial Thromboplastin Time (APTT) 
• 
Immature Platelet Fraction 
• 
Negative pregnancy test (serum hCG or urine) result in women of child bearing 
potential (must be done only once within 48 hours of enrollment) 
 
Prior to enrollment: 
• 
Bone marrow and/or lymph node biopsy confirming a diagnosis of MM, HL, or NHL at 
any time prior to HDT-AHCT. 
 
10.1 TREATMENT/INTERVENTION PLAN 
 
Patients will be enrolled prior to admission for HDT-AHCT, and they will undergo their 
planned AHCT for their respective hematologic malignancy as per institutional standards. 
A. Regardless of the conditioning regimen received, all patients will receive romiplostim 3.0 
mcg/kg SC on Day +1 and romiplostim 2.0 mcg/kg SC on Day +8 after HDT-AHCT. 
Beyond Day +8, patients will be treated until platelet count is >50,000/mcL, without any 
platelet transfusions in the prior 48 hours. All doses after the second romiplostim dose 
will be titrated as per Table 3, based on weekly CBC/platelet counts. Patients will receive 
a maximum of six weekly doses of romiplostim. 
B. Laboratory Assessments 
a. CBC, CMP, and Immature Platelet Fraction every day from day of AHCT (Day 0) 
until Day +15. All patients will get at least weekly (+/- 3 days) labs until Day +30. 
Patients who need 3 or more doses of romiplostim will get weekly (+/- 3 days) 
labs as long as their platelet count is ≥25,000. For patients who need 3 or more 
doses of romiplostim and whose platelet counts are <25,000 they will receive labs 
every second day until their platelets are ≥25,000. 
b. LDH, PT/INR, APTT every 7 days (+/-2 days) from Day +1 until Day +15. 
c.   CBC with differential, CMP, Immature Platelet Fraction, LDH, PT/INR, and APTT 
will be done at days +30 (+/- 7 days), +60 (+/- 7 days) and at +100 (+/-14 days) 
from AHCT. 
C. If there is a medical circumstance wherein the platelets decrease to <20,000/mcL, 
romiplostim can be resumed during hospitalization at the discretion of the treating 
physician for medical necessity. However, a patient will not exceed six total doses of 
romiplostim. 
D. If there is a medical circumstance (e.g. prolonged infection, sepsis, pneumonia) wherein 
a subject remains admitted for more than 30 days post-AHCT, which inhibits platelet 
recovery and platelet engraftment, daily labs will be discontinued and will instead be 
collected at least once weekly until discharge from hospital. 
E. Toxicity assessments will be done weekly until 7 days after the last dose of Romiplostim 
(Days +1, +8, +15, +22, +29, … +/- 2 days), and Days +30 (+/-7 days), +60 (+/-7 days), 
and +100 (+/- 14 days) from AHCT. 


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11.1 EVALUATION DURING TREATMENT/INTERVENTION 
 
The following assessments will be made during the study to assess efficacy and safety. See 
Table 4 Schedule of Assessments. 
Laboratory Assessments 
a. CBC with differential, CMP, and Immature Platelet Fraction every day from day of 
AHCT (Day 0) until day +15 All patients will get at least weekly (+/- 3 days) labs 
until day +30. Patients who need 3 or more doses of romiplostim will get weekly 
(+/- 3 days) labs as long as their platelet count is ≥25,000. For patients who need 
3 or more doses of romiplostim and whose platelet counts are <25,000 they will 
receive labs every second day until their platelets are ≥25,000. 
b. LDH, PT/INR, APTT every 7 days (+/-2 days) from Day +1 until Day +15. 
c. CBC with differential, CMP, Immature Platelet Fraction, LDH, PT/INR, and APTT 
will be done at days +30 (+/- 7 days), +60 (+/- 7 days) and at +100 (+/- 14 days) 
from AHCT. 
d. For women of childbearing potential, a pregnancy test (negative serum or urine 
hCG) must be done at the end of treatment visit, 7 days after the last dose of 
romiplostim. 
Safety endpoints will include change in typical neutrophil engraftment kinetics, venous or 
arterial thrombosis, evidence of marrow toxicity, and evidence of organ dysfunction. 
 
12.1 CRITERIA FOR REMOVAL FROM STUDY 
 
Treatment will continue until the occurrence of any of the following events: 
• 
Continuation is no longer in the patient’s best interest as determined by the patient’s 
treating oncologist. 
• 
Patient withdraws consent 
• 
Death 
• 
Lost to follow-up 
• 
Major violation of study protocol, such as non-compliance. 
• 
Adverse event(s) that, in the judgment of the Investigator or treating oncologist, may 
cause severe or permanent harm or which rule out continuation of the trial. 
 
Discontinuation of Romiplostim: 
 
If a patient develops a Grade 3/4 adverse event, attributable to romiplostim, based on the 
Common Terminology Criteria for Adverse Events (CTCAE version 5), the Romiplostim 
will be discontinued. 
If a patient develops an asymptomatic deep vein thrombosis and/or pulmonary embolism, 
or a symptomatic deep vein thrombosis and/or pulmonary embolism, not associated with 
hemodynamic instability, and not considered life-threatening, the romiplostim may be 
continued if there is consensus of judgment of the treating oncologist and study 
investigator. 


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13.0 
CRITERIA FOR OUTCOME ASSESSMENT AND ENDPOINT EVALUABILITY 
 
13.1 Criteria for Therapeutic Response/Outcome Assessment 
Primary Endpoint 
 
1) The number of days requiring platelet transfusions or grade 4 CTCAE thrombocytopenia 
following HDT-AHCT 
Secondary Endpoints 
 
1) The number of platelet transfusions issued during the AHCT admission 
 
2) The time to platelet engraftment after HDT-AHCT Platelet engraftment is defined as the 
first day of seven consecutive days with a platelet count of ≥20 K/mcL without transfusion 
support. 
 
3) The length of stay of AHCT 
 
4) The safety profile of romiplostim as per Section 11.0 Toxicities/Side Effects. 
 
Platelet transfusions will be at the discretion of the treating BMT attending at will not be 
specified in the protocol. However, a member of the investigator team will review the medical 
record to determine the reason for the transfusion, specified as (a) thrombocytopenia alone, 
(b) bleeding attributed, at least in part to thrombocytopenia, and/or (c) need for interventional 
procedure while thrombocytopenia is present. 
13.2 Criteria for Study Endpoint Evaluability 
All patients who enroll, and receive at least two dose of romiplostim, will be evaluable for 
primary and secondary endpoints. If a patient has enrolled, but does not receive two doses of 
romiplostim due to death, or change in medical status, they will not be evaluable and they will 
be replaced on the study. 
14.0 
BIOSTATISTICS 
 
This pilot study will investigate whether romiplostim reduces the number of days requiring 
platelet transfusions or grade 4 CTCAE thrombocytopenia following HDT-AHCT. The study 
includes patients with (1) MM undergoing high-dose melphalan and AHCT, (2) HL or NHL 
undergoing BEAM- or CBV-AHCT or (3) CNSL undergoing TBC-AHCT.  Further, at least 20 
will have MM undergoing high-dose melphalan and AHCT, and at least 20 will have HL or 
NHL undergoing BEAM-, CBV-, or TBC-AHCT. The primary endpoint along with the 
secondary endpoints will be evaluated in cohorts (1) MM and (2) HL or NHL separately. Due 
to anticipated low numbers, patients with CNSL receiving TBC-conditioning will be 
considered exploaratory only. 
The primary endpoint is the number of days post HDT-AHCT requiring transfusions or grade 
4 CTCAE thrombocytopenia. The study does not include a formal hypothesis test for the 
primary endpoint or corresponding decision rule. Instead the median and interquartile range 


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(IQR) of the number of days will be used to describe the number of days post HDT-AHCT 
requiring transfusions or grade 4 CTCAE thrombocytopenia for each cohort separately. The 
mean number of days along with a 95% confidence interval will additionally be reported. 
These summary statistics will be compared to the summary statistics of the historical data 
from patients transplanted from 2014-2016, presented in Table 1. For Cohort 1 (MM), the 
associated standard deviation for the mean of days post HDT-AHCT requiring transfusions or 
grade 4 CTCAE thrombocytopenia is 3.5. With 20 or more patients, the half width of the 95% 
confidence interval for the mean number of days for patients treated with  romiplostim is  +/- 
1.6 or less if a similar standard deviation is observed. For Cohort 2 (HL/NHL), the standard 
deviation is 4.7, corresponding to a half width of +/- 2.1 or less. While not formally comparing 
these data to the historical MSKCC data, observed improvements in the mean number of 
days requiring transfusions or grade 4 CTCAE thrombocytopenia will help design a larger 
phase II study to formally evaluate romiplostim in the HDT-AHCT setting. If the mean number 
of days requiring platelet transfusions decreases by at least 1.5 days for Cohort 1, and/or at 
least 2 days for Cohorts 2, this study will be considered sufficiently promising. We will then 
proceed with a phase II trial for the cohort or cohorts that reached the above criteria (i.e. the 
specified decrease in days requiring platelet transfusion). 
Evaluability criteria for both the primary and secondary endpoints are provided in Section 13.2. 
In addition to the primary endpoint, the pilot study includes a number of secondary objectives. 
1. 
To estimate the median and mean number of platelet transfusions issued during 
AHCT admission. In addition to the mean, the 95% confidence interval will be 
reported.This will be reported separately for each cohort. 
2. 
To estimate the median and mean time to platelet engraftment after AHCT.  In 
addition to the mean, the 95% confidence interval will be reported.This will be 
reported separately for each cohort. 
3. 
To estimate the  median and mean AHCT length of stay.  In addition to the mean, the 
95% confidence interval will be reported.This will be reported separately for each 
cohort. 
4. 
To describe the safety and toxicity profile of romiplostim in this patient population. 
Toxcitiy will be described by grade and will be reported separately for each cohort. 
15.1 TOXICITIES/RISKS/SIDE EFFECTS 
 
Based on our initial experience, we have not observed treatment-related toxicities in our 
patients treated with romiplostim for CIT.  Based on the romiplostim Prescribing Information, 
the most common adverse reactions (≥ 5% higher patient incidence in romiplostim versus 
placebo) are arthralgia, dizziness, insomnia, myalgia, pain in extremity, abdominal pain, 
shoulder pain, dyspepsia, and paresthesia. 
Individual cases of thrombosis and been reported in patients receiving romiplostim, but in 
one recent review of long-term use of romiplostim, “The thrombotic adverse event rate 


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across all studies was 0.09 events per 100 patient-weeks on romiplostim therapy,” markedly 
lower than would expected in patients with active cancer receiving chemotherapy. We have 
not observed an increased thrombosis rate compared with expected rates in patients with 
metastatic cancer, on chemotherapy, however, we will monitor any clinical evidence of 
thrombosis as well as hemorrhage. 
Assessment of potential toxicity will be based on the Common Terminology Criteria for 
Adverse Events (CTCAE) Version 5.  We will monitor for evidence of marrow toxicity, with 
weekly CBC (CBC must include: WBC, Hgb, platelet, MCV, cell differential) and lab toxicities 
of grade 3/4 will be adjudicated on a regular basis by the PI or Co-PI of the study. 
Toxicity assessments will be done weekly (+/- 3 days while COVID restrictions remain in 
place) until 7 days after the last dose of Romiplostim, and Days +30 (+/-7 days), +60 (+/-7 
days), and +100 (+/- 14 days) from AHCT. If a patient is discontinuing 
chemotherapy/treatment and going to hospice/ comfort care, the final toxicity assessments 
will be omitted if toxicities were managed regularly. 
The study will report all toxicities from the time a patient signs consent until 30 days after the 
last dose of treatment, unless they are at least possible related to the protocol, in which case 
they will be reported beyond the 30-day period. All toxicities meeting these criteria should be 
reported to MSKCC as a toxicity in CRDBi-Multicenter with supporting source 
documentation. 
Longterm safety follow up for secondary malignancy is not planned within this protocol 
because the patients enrolled will be followed as part of their standard of care on the Adult 
Bone Marrow Transplant Service at MSKCC. 
15.1 
Serious Adverse Event (SAE) Reporting 
 
An adverse event is considered serious if it results in ANY of the following outcomes: 
• 
Death 
• 
A life-threatening adverse event 
• 
An adverse event that results in inpatient hospitalization or prolongation of existing 
hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect 
• 
Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical judgment, 
they may jeopardize the patient or participant and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition 
 
Note: Hospital admission for a planned procedure/disease treatment is not considered an 
SAE. 


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SAE reporting is required as soon as the participant starts investigational 
treatment/intervention. SAE reporting is required for 30-days after the participant’s last 
investigational treatment/intervention. Any event that occur after the 30-day period that is 
unexpected and at least possibly related to protocol treatment must be reported. 
 
Please note: Any SAE that occurs prior to the start of investigational treatment/intervention 
and is related to a screening test or procedure (i.e., a screening biopsy) must be reported. 
 
All patients will be followed for safety and toxicity related to the study drug (romiplostim). 
Potentially serious toxicities are an expected part of autologous stem cell transplantation.  
The reportable adverse events (AEs) and serious adverse events (SAEs) associated with 
autologous stem cell transplantation will be defined according to the Adult Bone Marrow 
Transplant (ABMT) Adverse Event (AE) and Serious Adverse Event (SAE Guide). The ABMT 
AE and SAE Guide is posted as a Standard Working Procedure (SWP) on the Clinical 
Research Policies and Regulations page: 
https://one.mskcc.org/sites/pub/clinresearch/Policies/Departmental%20SOPs/Adult%20BMT 
%20AE%20and%20SAE%20Guide.pdf 
 
All SAEs must be submitted in PIMS. If an SAE requires submission to the HRPP office per 
IRB SOP RR-408 ‘Reporting of Serious Adverse Events’, the SAE report must be submitted 
within 5 calendar days of the event.  All other SAEs must be submitted within 30 calendar 
days of the event. 
The report should contain the following information: 
 
• 
The date the adverse event occurred 
• 
The adverse event 
• 
The grade of the event 
• 
Relationship of the adverse event to the treatment(s) 
• 
If the AE was expected 
• 
Detailed text that includes the following 
o An explanation of how the AE was handled 
o A description of the participant’s condition 
o Indication if the participant remains on the study 
• 
If an amendment will need to be made to the protocol and/or consent form 
• 
If the SAE is an Unanticipated Problem 
 
15.2. External SAE Reporting 
 
The MSKCC research staff must inform Amgen, Inc. of any Suspected Unexpected Serious 
Adverse Reaction (SUSAR) as soon as possible but no later than 5 calendar days of the 
MSKCC principal investigator becoming aware of the event. All SUSARs will be reported up 
to 30 days after the last dose of treatment, unless they are at least possibly related to the 
protocol, in which case they will be reported beyond the 30-day period. 


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The MSKCC research staff must also inform Amgen, Inc. of any pregnanacy or exposure to 
drug through lactation and the associated reports and outcomes (i.e. unexpected pregnancy, 
pregnancy of partner, spontaneous abortion, congenital abnormality etc.). This report must 
be sent to Amgen Safety within 1 business day of MSKCC research staff awareness for 
reports meeting serious criteria, and is not to exceed 15 calendar days of MSKCC research 
staff awareness for non-serious reports. 
16.1 PROTECTION OF HUMAN PARTICIPANTS 
 
Inclusion of Children in Research: 
This protocol/project does not include children because the number of children is limited and 
the majority are already accessed by a nationwide pediatric cancer research network. This 
statement is based on exclusion 4b of the NIH Policy and Guidelines on the Inclusion of 
Children as Participants in Research Involving Human Subjects. 
 
Incentives/Costs/Benefits: 
No incentives will be offered to patients/subjects for participation in this study. Participation is 
voluntary. The potential benefits of participation in the study will be weighed against other 
treatment options (see below) including supportive care. The patient/subject or their health 
insurance provider will be responsible for the costs of standard medical care including MD 
visits, routine blood tests, administration of the study drug, and bone marrow biopsies and 
aspirates. The patient/subject or their health insurance provider will not be charged for the 
study drug romiplostim. 
 
Alternative treatment of patients:  Usual care with transfusion of platelets when necessary as 
deemed by treating oncologist. 
 
16.1 
Privacy 
 
MSK’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form. The use and disclosure of 
protected health information will be limited to the individuals/entities described in the 
Research Authorization form. A Research Authorization form must be approved by the IRB 
and Privacy Board (IRB/PB). 
The consent indicates that individualized  de identified information collected for the purposes 
of this study may be shared with other qualified researchers. Only researchers who have 
received approval from MSK will be allowed to access this information which will not include 
protected health information, such as the participant’s name, except for dates. It is also 
stated in the Research Authorization that their research data may be shared with others at 
the time of study publication. 
 
 
16.2 
Data Management 
 
A Clinical Research Coordinator (CRC) will be assigned to the study at MSKCC. The 
responsibilities of the CRC include project compliance, data collection, abstraction and entry, 
data reporting, regulatory monitoring, problem resolution and prioritization, and coordinate 
the activities of the protocol study team. 


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The data collected for this study will be entered into a secure database, Medidata Rave. 
Source documentation will be available to support the computerized patient record. 
Investigators will permit study-related audits by the sponsor, IRB review, and regulatory 
inspection(s) (e.g., FDA, EMEA, TPP), providing direct access to the facilities where the 
study took place, to the source documents, and to all other study documents. 
Final data sets for publication are required to be locked and stored centrally for potential 
future access requests from outside entities. 
16.3 
Quality Assurance 
 
Weekly registration reports will be generated to monitor patient accruals and completeness of 
registration data. Routine data quality reports will be generated to assess missing data and 
inconsistencies. Accrual rates, the extent and accuracy of evaluations and follow-ups will be 
monitored periodically throughout the study period for potential problems, which will be brought 
to the attention of the study team for discussion and action. 
Random-sample data quality and protocol compliance audits will be conducted by the study 
team, at a minimum of two times per year, or more frequently if indicated. 
 
16.4 
Data and Safety Monitoring 
 
The Data and Safety Monitoring Plan utilized for this study must align with the MSK DSM  
Plan, where applicable. 
 
The Data and Safety Monitoring (DSM) Plans at Memorial Sloan Kettering were approved by 
the National Cancer Institute in August 2018. The plans address the new policies set forth by 
the NCI in the document entitled “Policy of the National Cancer Institute for Data and Safety  
Monitoring  of Clinical Trials.” 
 
There are several different mechanisms by which clinical studies are monitored for data, 
safety and quality. At a departmental/PI level there exists procedures for quality control by 
the research team(s). Institutional processes in place for quality assurance include protocol 
monitoring, compliance and data verification audits, staff education on clinical research QA 
and two institutional committees that are responsible for monitoring the activities of our 
clinical trials programs. The committees: Data and Safety Monitoring Committee (DSMC) for 
Phase I and II clinical trials, and the Data and Safety Monitoring Board (DSMB) for Phase III 
clinical trials, report to the Deputy Physician-in-Chief,  Clinical Research. 
 
During the protocol development and review process, each protocol will be assessed for its 
level of risk and degree of monitoring required. 
The MSK DSMB monitors phase III trials and the DSMC monitors non-phase III trials.  The 
DSMB/C have oversight over the following trials: 
• 
MSK Investigator Initiated Trials (IITs; MSK as sponsor) 
• 
External studies where MSK is the data coordinating center 


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• 
Low risk studies identified as requiring DSMB/C review 
 
The DSMC will initiate review following the enrollment of the first participant/or by the end of 
the year one if no accruals and will continue for the study lifecycle until there are no 
participants under active therapy and the protocol has closed to accrual. The DSMB will 
initiate review once the protocol is open to accrual. 
The MSKCC research staff will submit to Amgen, Inc. annual safety reports. These reports 
will include SUSARs and pregnancy and lactation exposure (and any associated 
reports/outcomes). The reports will be sent to the NASCR Manager once per year and at the 
end of the study. Any other report containing safety data generated during the course of the 
study will also be sent to Amgen, Inc. at the time of submission to any body governing 
research conduct. A final end of study safety report will be sent to Amgen, Inc. at the time of 
submission to any body governing but no later than 1 calendar year past study completion. 
17.0 
REFERENCES 
 
1. 
Landau H, Giralt S. Treatment of Transplant-Eligible Patients with Multiple Myeloma in 2014. 
Hematol Oncol Clin North Am. 2014;28(5):815-827.  doi:10.1016/j.hoc.2014.06.004. 
2. 
Shah N, Callander N, Ganguly S, et al. Hematopoietic Stem Cell Transplantation for Multiple 
Myeloma: Guidelines from the American Society for Blood and Marrow Transplantation. Biol 
Blood Marrow Transplant. 2015;21(7):1155-1166.  doi:10.1016/j.bbmt.2015.03.002. 
3. 
Oliansky DM, Czuczman M, Fisher RI, et al. The role of cytotoxic therapy with hematopoietic 
stem cell transplantation in the treatment of diffuse large B cell lymphoma: update of the 2001 
evidence-based review. Biol Blood Marrow Transplant. 2011;17(1):20-47.e30. 
doi:10.1016/j.bbmt.2010.07.008. 
4. 
Majhail NS, Farnia SH, Carpenter PA, et al. Indications for Autologous and Allogeneic 
Hematopoietic Cell Transplantation: Guidelines from the American Society for Blood and 
Marrow Transplantation. Biol Blood Marrow Transplant. 2015;21(11):1-7. 
doi:10.1016/j.bbmt.2015.07.032. 
5. 
Chen Y-B, Lane A a, Logan BR, et al. Impact of conditioning regimen on outcomes for 
patients with lymphoma undergoing high-dose therapy with autologous hematopoietic cell 
transplantation. Biol Blood Marrow Transplant. 2015;21(6):1046-1053. 
doi:10.1016/j.bbmt.2015.02.005. 
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Perales M-A, Ceberio I, Armand P, et al. Role of Cytotoxic Therapy with Hematopoietic Cell 
Transplantation in the Treatment of Hodgkin Lymphoma: Guidelines from the American 
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2015;21(6):971-983.   doi:10.1016/j.bbmt.2015.02.022. 
7. 
Omuro A, Correa DD, DeAngelis LM, et al. R-MPV followed by high-dose chemotherapy with 
TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 
2015;125(9):1403-1410.   doi:10.1182/blood-2014-10-604561. 
8. 
Scordo M, Bhatt V, Hsu M, et al. A Comprehensive Assessment of Toxicities in Patients with 
Central Nervous System Lymphoma Undergoing Autologous Stem Cell Transplantation Using 
Thiotepa, Busulfan, and Cyclophosphamide Conditioning. Biol Blood Marrow Transplant. 


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IRB Number: 20-180 A(9) 
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2017;23(1):38-43.   doi:10.1016/j.bbmt.2016.09.024. 
9. 
DeFilipp Z, Li S, El-Jawahri A, et al. High-dose chemotherapy with thiotepa, busulfan, and 
cyclophosphamide and autologous stem cell transplantation for patients with primary central 
nervous system lymphoma in first complete remission. Cancer. 2017;123(16):3073-3079. 
doi:10.1002/cncr.30695. 
10. 
Kuter DJ. Managing  Thrombocytopenia Associated With Cancer Chemotherapy. Cancer 
Netw.  2015:1-17.  http://www.cancernetwork.com/oncology-journal/managing- 
thrombocytopenia-associated-cancer-chemotherapy. 
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Gajewski JL, Johnson V V., Sandler SG, Sayegh A, Klumpp TR. A review of transfusion 
practice before, during, and after hematopoietic progenitor cell transplantation. Blood. 
2008;112(8):3036-3047.   doi:10.1182/blood-2007-10-118372. 
12. 
Tay J, Allan D, Beattie S, et al. Rationale and design of platelet transfusions in 
haematopoietic stem cell transplantation: the PATH pilot study. BMJ Open. 
2016;6(10):e013483.   doi:10.1136/bmjopen-2016-013483. 
13. 
Broudy VC, Lin NL. AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl. 
Cytokine. 2004;25(2):52-60.  doi:10.1016/j.cyto.2003.05.001. 
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Kuter DJ. Biology and Chemistry of Thrombopoietic Agents. Semin Hematol. 2010;47(3):243- 
248.  doi:10.1053/j.seminhematol.2010.02.005. 
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Bussel JB, Kuter DJ, George JN, et al. AMG 531, a thrombopoiesis-stimulating protein, for 
chronic ITP. N Engl J Med. 2006;355:1672-1681. doi:10.1056/NEJMoa054626. 
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Bussel JB, Kuter DJ, Pullarkat V, Lyons RM, Guo M, Nichol JL. Safety and efficacy of long- 
term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood. 
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Elting LS, Rubenstein EB, Martin CG, et al. Incidence, cost, and outcomes of bleeding and 
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thrombocytopenia. J Clin Oncol. 2001;19(4):1137-1146. 
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Parameswaran R, Lunning M, Mantha S, et al. Romiplostim for management of 
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Soff GA, Miao Y, Devlin SM, et al. Romiplostim for Chemotherapy-Induced Thrombocytopenia 
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18.0 
APPENDICES 
 
Appendices will be stored in a separate file and will be submitted in electronic and/or paper 
format. 
Appendix A: Investigators Brochure 


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Memorial Sloan Kettering Cancer Center 
IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
 
 
 
19.0 
MSK MULTICENTER TRIAL ADDENDUM 
 
Data analysis being performed by the site(s): "Clinical, laboratory and radiographic data will be 
shared with SYLVESTER COMPREHENSIVE CANCER CENTER, including but not limited to: 
cancer therapy, COVID-19 treatment, demographic information, and assessment values." 
Dr. Gerald A Soff MD (Clinical Director, Hemostasis, Thrombosis and Transfusion Services, 
University of Miami Health System/Sylvester Comprehensive Cancer Center) will serve as a Data 
Collaborator for this study. In this capacity, he will participate in analysis, presentation, and 
publication of the data and findings of the study. He will also contribute to the language for 
amendments to the protocols, if necessary. 
Dr. Soff will not have access to any Protected Health Information (PHI) on any patient. He will have 
access to aggregated data only. All correspondences between the MSKCC investigators and Dr. 
Soff will be conducted via secure email. Data will be made available to Dr. Soff throughout the 
performance of the study, as well as during the period when the data are analyzed and written up for 
presentation and publication. 


Memorial  Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 23 of 24 
 
 
 
 
Table 4. Schedule of Study Assessments 
Memorial Sloan Kettering Cancer Center 
IRB Number: 20-180 A(9) 
Approval date: 15-Sep-2021 
 
Study Assessments/ 
Testing 
Screening 
Within 28 
days of 
AHCT 
Admission 
Day of AHCT 
Admission 
Day 0 
Day of 
AHCT 
Daily  from Day 
0 until Day 
+157. 
Weekly  from 
Day +1 until 
last doseof 
Romiplostim8. 
End of 
Treatment 
7 Days after 
last doseof 
Romiplostim 
(+/- 3d) 
Day (d) Post-AHCT 
d +21 
(+/- 3d) 
d +30 
(+/- 7d) 
d +60 
(+/- 7d) 
d+100 
(+/- 14d) 
Consultation with Adult BMT Physician 
X 
Sign informed consent 
X 
History, 
X 
Physical Exam 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
ECOG performance status 
X 
X11 
X 
X 
Confirmation of diagnosis1 
X 
CBC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CMP 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
LDH 
X 
X9 
X 
X 
X 
X 
PT/INR and APTT 
X 
X10 
X 
X 
X 
X 
Immature Platelet Fraction 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Cytogenetics2 
X 
X3 
Romiplostim injection4 
X 
Adverse Event Assessments 
X 
X 
X 
X 
X 
X 
Pregnancy Test5 
X6 
X 
X 
X 
X 
Pulmonary Function Test 
X 
MUGA or Resting Echocardiogram 
X 
1 Bone marrow and/or lymph node and/ortissue biopsy confirming a diagnosis of MM, HL, or NHL atany time prior to HDT-AHCT. 
2 If never previously done, a baseline cytogenetics will be drawn during screening. The cytogenetic testing will include the FISH panel for MDS froma bone marrow aspirate and/orbiopsy or peripheral bloodtesting. 
3 A repeat cytogenetics will be drawn on Day +100 (+/-14 days) from AHCT only if there is evidence of romiplostim toxicity tothe bone marrow. Appearance of leukoerythroblastosis on the peripheral blood, will be 
considered a surrogate for possible romiplostim toxicity tothe bone marrow. Leukoerythroblastic changes consist of immature white cells, nucleated red blood cells, orincrease inteardrop cells (dacrocytes). 


Memorial  Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 24 of 24 
 
 
MSK IRB#: 20-180 A(9), Approval Date: 15-Sep-2021 
 
 
4 All patients will receive romiplostim 3.0 mcg/kg SC on Day +1 and romiplostim 2.0 mcg/kg SC on Day +8 after HDT-AHCT. Beyond Day +8 patients will be treateduntil platelet countis >50,000/mcL, without any 
platelettransfusions inthe prior 48 hours. All doses after the secondromiplostimdose will be titrated as per Table 3, based on weekly CBC/platelet counts. Patients will receive a maximum of six weeklydoses of 
romiplostim. Romiplostim doses after Day +8 may have a +2 day window 
5 For women of childbearing potential, a negative pregnancy test (serum orurine b-HCG) mustbe done atthe timepoints specified inthe calendar. 
6 The screening pregnancy testmust be done within 48 hours of AHCT 
7 For patients who need 3 ormore doses of romiplostim and whose platelet counts are <25,000 they will receive labs every second day beyond Day +15 until their platelets are ≥25,000. 
8 While COVID restrictions remainin place, weekly physicianvisits will have a windowing of +/- 3 days. 
9 LDH only needed weekly until Day +15. 
10 PT/INR and APTT only neededweekly until Day +15. 
11 ECOG only requiredfor outpatient visits.