• Dose Limiting Toxicity (DLT) [ Time Frame: up to 28 days in Cycle 1 ]
  Number of subjects with a DLT
• Maximum tolerated dose (MTD) [ Time Frame: up to 28 days in cycle 1 ]
  The highest dose of CC-99282 associated with acceptable safety and tolerability
• Adverse Events (AEs) [ Time Frame: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 2 years) ]
  Type, frequency, seriousness, severity and relationship of AEs to CC-99282 and rituximab; changes from baseline in clinically-relevant physical findings, vital signs, selected analytes, ECGs, LVEF and ECOG

• Pharmacokinetics - Cmax [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
  Maximum observed plasma concentration
• Pharmacokinetics - AUC [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
  Area under the plasma concentration-time curve
• Pharmacokinetics - Tmax [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
  Time to Cmax
• Pharmacokinetics - t1/2 [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
  Terminal-phase elimination half-life
• Pharmacokinetics - CL/F [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
  Apparent total clearance of the drug from plasma after oral administration
• Pharmacokinetics - V/F [ Time Frame: Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days) ]
  Apparent volume of distribution during terminal phase after non-intravenous administration
• Objective response rate (ORR) [ Time Frame: up to approximately 3 years ]
  Sum of partial response (PR) plus complete response (CR) determined by the Lugano Classification for NHL and by the modified International PCNSL collaborative Group (IPCG) criteria
• Time to response (TTR) [ Time Frame: up to approximately 3 years ]
  Time from first dose of CC-99282 to the first documentation of response ≥ PR
• Duration of response (DoR) [ Time Frame: up to approximately 3 years ]
  Time from first documentation of response (≥ PR) to the first documentation of PD or death
• Progression free survival [ Time Frame: up to approximately 3 years ]
  Time from first dose of CC-99282 to the first occurrence of disease progression or death from any cause
• Overall survival [ Time Frame: up to approximately 3 years ]
  Time from first dose of CC-99282 to death from any cause

Subjects with R/R NHL who have failed at least 2 lines of therapy (or have received at least one prior line of standard therapy and are not eligible for any other therapy).

The dose escalation will evaluate the safety and tolerability of escalating doses of CC-99282 in R/R DLBCL and/or R/R FL subjects to determine the MTD of CC-99282 as monotherapy.

The dose expansion will further evaluate the safety and preliminary efficacy of single agent CC-99282 administered at or below MTD in subjects with R/R DLBCL and NHL. Part B will also evaluate the safety and preliminary efficacy of CC-99282 in combination with rituximab in subjects with R/R DLBCL and R/R FL.

• Drug: CC-99282
  CC-99282
• Drug: rituximab
  rituximab

• Experimental: Administration of CC-99282
  Escalating doses of CC-99282 administered orally once daily on intermittent schedules up to 2 years.
  Intervention: Drug: CC-99282
• Experimental: CC-99282 + rituximab
  CC-99282 administered orally once daily on intermittent schedule with rituximab intravenously (IV) 375 mg/m2 weekly in Cycle 1, every 28 days in C2-6, then every 8 weeks through 2 years.
  Interventions:

  • Drug: CC-99282
  • Drug: rituximab

Inclusion Criteria:

1. Subject is ≥18 years of age at the time of signing the informed consent form (ICF).
2. Subject has a history of NHL with relapsed or refractory disease
3. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

4. Subjects must have the following laboratory values:

   1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support for 7 days (14 days if pegfilgastrim)
   2. Hemoglobin (Hgb) ≥ 8 g/dL
   3. Platelets (plt) ≥ 75 x 109/L without transfusion for 7 days
   4. Serum bilirubin ≤ 1.5 x ULN (upper limit of normal).
   5. AST/SGOT and ALT/SGPT ≤ 2.5X ULN
   6. Estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault equation.
5. Agree to follow the CC-99282 Pregnancy Prevention Plan (PPP)

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Subject has life expectancy ≤ 2 months.
2. Subject has received prior systemic anti-cancer treatment (approved or investigational) ≤ 5 half-lives or 4 weeks prior to starting CC-99282, whichever is shorter.
3. Subject has symptomatic CNS involvement of disease (does not apply to PCNSL subjects in Part B).
4. Persistent diarrhea or malabsorption≥ Grade 2 , despite medical management
5. Subject is on chronic systemic immunosuppressive therapy or corticosteroids (eg, prednisone or equivalent not to exceed 10 mg per day within the last 14 days) or subjects with clinically significant graft-versus-host disease (GVHD).
6. Subject had prior autologous SCT ≤ 3 months prior to starting CC 99282. If subject had prior autologous SCT > 3 months prior to the start of CC-99282, any treatment-related toxicity is unresolved (grade > 1).
7. Subject had prior allogeneic SCT with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-99282. If subject had prior allogenic SCT > 6 months prior to the start of CC-99282, any treatment-related toxicity is unresolved (grade > 1).
8. Impaired cardiac function or clinically significant cardiac disease