Clinical trial NCT02031419: Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-cell Lymphoma and Follicular Lymphoma
Official title: A Phase 1B, Multi-Center, Open-Label Study of Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lymphoma, Large B-Cell, Diffuse
Keywords: CC-122
CC-223
CC-292
Rituximab
Lymphoma
Diffuse Large B-Cell Lymphoma
Lenalidomide naïve Follicular Lymphoma
Lenalidomide exposed Follicular Lymphoma
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2014-01-09
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: First study, at multiple clinical centers, exploring the effects of different combinations of compounds (CC-122, CC-223 ,CC-292 and rituximab) to treat Diffuse Large B Cell Lymphoma (DLBCL) and Follicular Lymphoma

Detailed description: Study CC-122-DLBCL-001 is a Phase 1b dose escalation and expansion clinical study of CC 122, CC-223 and CC-292 administered orally as doublets with or without rituximab, in participants with relapsed/refractory DLBCL who have failed standard therapy.

In expansion phase, selected combination will be administered to lenalidomide naïve FL participants and lenalidomide exposed FL participants in addition to relapsed/refractory DLBCL participants.

Eligibility criteria: Inclusion Criteria:

* Men and women, 18 years or older, with histologically or cytologically-confirmed either:

  1. Chemo-refractory DLBCL (including transformed low grade lymphoma)
  2. Lenalidomide naïve; relapsed or refractory CD20-positive follicular lymphoma (Grade 1, 2, or 3a) following at least one prior standard systemic treatment regimen including systemic chemo-, immune-; or chemo-immunotherapy and at least one prior line of salvage therapy with no prior exposure to lenalidomide, or double-refractory FL participants with no prior exposure to lenalidomide (FL-1 cohort)
  3. Lenalidomide exposed: relapsed or refractory CD20-positive follicular lymphoma (Grade 1, 2, or 3a) previously treated with at least two cycles of lenalidomide-containing regimen (FL-2 cohort), either as a single agent or in combination
* At least one site of measurable disease
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
* Participants must have the following laboratory values:
* Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L or ≥ 1.0 x 109/L (with bone marrow involvement with DLBCL)
* Hemoglobin (Hgb) ≥ 8 g/dL.
* Potassium within normal limits
* Asparate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) and Alanine Aminotransferase/Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 X ULN if liver tumor is present.
* Serum bilirubin ≤ 1.5 x ULN.
* Estimated serum creatinine clearance of ≥ 50 mL/min
* Participants must have the following laboratory values:

Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L without growth factor support for 7 days (14 days if participants received pegfilgrastim).

* Males enrolled into treatment arms receiving CC-122 must: Agree to abstain from donating sperm while taking IP and for at least 95 days following discontinuation of IP

Exclusion Criteria:

* Symptomatic central nervous system involvement.
* Known symptomatic acute or chronic pancreatitis.
* Persistent diarrhea or malabsorption despite medical management.
* Peripheral neuropathy ≥ grade 2
* Impaired cardiac function or clinically significant cardiac diseases
* Participants with diabetes on active treatment (for participants treated on CC-223 containing arms only)
* Prior autologous stem cell transplant (ASCT) ≤ 3 months before first dose.
* Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning.
* Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks prior to starting study drugs, whichever is shorter.
* Participants who have undergone major surgery ≤ 2 weeks prior to starting study drugs.
* Women who are pregnant or breast feeding. Adults of reproductive potential not willing to employ two forms of birth control.
* Participants with known HIV infection, chronic active hepatitis B or C virus (HBV/HCV) infection.
* Participants with treatment-related myelodysplastic syndrome.
* History of concurrent second cancers requiring active, ongoing systemic treatment.
* Prior treatment with a dual mTORC1/mTORC2 inhibitor (CC-223 arms only) or BTK inhibitor (PCI-32765) (CC-292 arms only). \[Prior treatment with rapamycin analogues, PI3K or AKT inhibitors, lenalidomide and rituximab are allowed\].

Primary outcomes:
measure: Safety
timeFrame: From the time of informed consent, throughout dosing period and for 28 days after the last dose of study drug.
Secondary outcomes:
measure: Efficacy
timeFrame: Every 2-3 months until proof of tumor progression
measure: Pharmacokinetics - CC-223 and CC-292 interaction
timeFrame: Day 1, Day 15
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: Local Institution - 005
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Nashville
country: United States
facility: Local Institution - 001
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: Local Institution - 007
state: Wisconsin
city: Edmonton
country: Canada
facility: Local Institution - 402
state: Alberta
city: Toronto
country: Canada
facility: Local Institution - 400
state: Ontario
city: Bordeaux
country: France
facility: Local Institution - 102
city: Lyon
country: France
facility: Local Institution - 101
city: Villejuif CEDEX
country: France
facility: Local Institution - 100
city: Milano
country: Italy
facility: Local Institution - 202
city: Rozzano (MI)
country: Italy
facility: Local Institution - 200
city: Turin
country: Italy
facility: Local Institution - 201
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: