Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-cell Lymphoma and Follicular Lymphoma
Lymphoma, Large B-Cell, Diffuse
About this trial
This is an interventional treatment trial for Lymphoma, Large B-Cell, Diffuse focused on measuring CC-122, CC-223, CC-292, Rituximab, Lymphoma, Diffuse Large B-Cell Lymphoma, Lenalidomide naïve Follicular Lymphoma, Lenalidomide exposed Follicular Lymphoma
Eligibility Criteria
Inclusion Criteria:
Men and women, 18 years or older, with histologically or cytologically-confirmed either:
- Chemo-refractory DLBCL (including transformed low grade lymphoma)
- 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)
- 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 3 months 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].
Sites / Locations
- Stanford Cancer Center
- Yale Cancer Center
- Local Institution - 005
- Northwestern University
- Mayo Clinic
- Local Institution - 001
- MD Anderson Cancer Center
- Local Institution - 007
- Local Institution - 402
- Local Institution - 400
- Local Institution - 102
- Local Institution - 101
- Local Institution - 100
- Local Institution - 202
- Local Institution - 200
- Local Institution - 201
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
CC-122 + CC-223 +/- rituximab
CC-122 + CC-292 +/- rituximab
CC-292 + CC-223 +/- rituximab
CC-122 + rituximab
CC-122 administered orally once daily at 2mg or 3 mg in combination with CC-223 administered orally once daily at 20mg or 30 mg with or without Rituximab administered by IV once every 28 days
CC-122 administered orally once daily at 2mg or 3 mg in combination with CC-292 administered orally twice daily at 500 mg with or without Rituximab administered by IV once every 28 days
CC-292 administered twice daily at 500 mg in combination with CC-223 administered orally once daily at 20mg or 30 mg with or without Rituximab administered by IV once every 28 days
CC-122 administered orally once daily in combination with Rituximab.