Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-cell Lymphoma and Follicular Lymphoma

Launched by CELGENE · Jan 7, 2014

Keywords

ClinConnect Summary

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.

Gender

ALL

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). \[Prior treatment with rapamycin analogues, PI3K or AKT inhibitors, lenalidomide and rituximab are allowed\].