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

• Status: Active, not recruiting
• Trial end date: 2022-11-30
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Celgene; Celgene Corporation
• Treatments: Rituximab; Spebrutinib

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 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].