Ensayos clínicos

Inclusion Criteria:

• Biopsy proven Diffuse large B-cell lymphoma (DLBCL) (including transformed low grade lymphoma)
• Relapsed or refractory to prior standard treatment regimens
• At least one site of measurable disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
• Subjects 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
• Subjects 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 subject 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
• Subjects with diabetes on active treatment (for subjects 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.
• Subjects 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.
• Subjects with known HIV infection, chronic active hepatitis B or C virus (HBV/HCV) infection.
• Subjects 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].