This is a Phase 1b study consisting of 2 parts: a dose escalation (Part 1) of CC-220 or CC-99282 added to the standard R-CHOP-21 regimen for first-line treatment of a-BCL. The dose escalation (Part 1) will consist of 2 parallel arms in combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP-21); CC-220 and R-CHOP-21 or CC-99282 and R-CHOP-21. Part 1 will be followed by a randomized dose expansion (Part 2) with CC-220 and/or CC-99282 at the Recommended Phase 2 Dose (RP2D) in combination with R-CHOP-21. A polatuzumab-R-CHP regimen in combination with CC-220 or CC-99282 will be explored with the addition of a new cohort only after the RP2D for the CC-220 and/or CC-99282 and R-CHOP-21 combination has been defined.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
224
CC-220 by mouth at the assigned dose starting on Day 1 for 14 consecutive days of the 21-day treatment cycle for 6 cycles of treatment.
Rituximab 375 mg/m2 on Day 1 by intravenous (IV) infusion or 1400 mg (SC) subcutaneous (from Cycle 2) of a 21-day treatment cycle for up to a total of 6 cycles
Cyclophosphamide 750mg/m2 on Day 1 by IV infusion of a 21-day treatment cycle for up to a total of 6 cycles
Doxorubicin 50 mg/m2 IV infusion on Day 1 of a 21-day treatment cycle for up to a total of 6 cycles
Vincristine 1.4 mg/m2 (maximum of 2.0 mg total) IV intravenous on Day 1 of a 21-day treatment cycle for up to a total of 6 cycles
Prednisone 100 mg PO on Days 1 through 5 of each 21-day treatment or 100mg IV on Day 1 is also acceptable for up to a total of 6 cycles
CC-99282 by mouth at the assigned dose starting on Day 1 for 7 consecutive days of the 21-day treatment cycle for 6 cycles of treatment.
Polatuzumab vedotin 1.8 mg/kg on Day 1 by intravenous (IV) infusion of a 21-day treatment cycle for up to a total of 6 cycles
Rituximab 375 mg/m2 on Day 1 by intravenous (IV) infusion of a 21-day treatment cycle for up to a total of 6 cycles
Local Institution - 162
Birmingham, Alabama, United States
NOT_YET_RECRUITINGMayo Clinic - Arizona
Scottsdale, Arizona, United States
RECRUITINGLocal Institution - 169
Duarte, California, United States
NOT_YET_RECRUITINGMayo Clinic - Jacksonville
Jacksonville, Florida, United States
Maximum Tolerated Dose (MTD) - Part 1
Frequency of dose-limiting toxicities (DLT) associated with addition of iberdomide (CC-220) to R-CHOP-21 therapy and the addition of CC-99282 to R-CHOP-21 therapy
Time frame: During the first 2 cycles of treatment (each cycle is 21 days)
Recommended Phase 2 Dose (RP2D) - Part 1
Defined as the dose that will be selected for dose expansion based on MTD
Time frame: During the first cycle of treatment (each cycle is 21 days)
Safety and tolerability of CC-220 and CC-99282 at RP2D - Part 2
AEs evaluated using NCI CTCAE criteria, v. 5.0, including treatment -emergent adverse events (TEAEs) and laboratory assessments
Time frame: From the first dose of any IP until 28 days after the last dose of IP
Maximum Tolerated Dose (MTD) - Part 2A
Frequency of DLTs associated with addition of iberdomide (CC-220) to polatuzumab-R-CHP therapy and the addition of CC-99282 to polatuzumab-R-CHP therapy
Time frame: During the first cycle of treatment (each cycle is 21 days)
Recommended Phase 2 Dose (RP2D) - Part 2A
Defined as the dose that will be selected for dose expansion based on MTD
Time frame: During the first cycle of treatment (each cycle is 21 days)
Best overall response rate (ORR)
The proportion of participants with best overall response achieved during the study as either Complete Response or Partial Response before subsequent anti-lymphoma therapy
Time frame: Up to 4 years
Complete Metabolic Response Rate (CMRR)
The proportion of participants experiencing complete metabolic response (CMR) before receiving any subsequent anti-lymphoma therapy
Time frame: Up to 4 years
Time to Response (TTR)
The time from entry to the study (enrollment date for Part 1 and randomization date for Part 2) to the date of first documented response (≥ PR)
Time frame: Up to 4 years
Duration of Response (DOR)
The time from the earliest date of documented response (≥ PR) to the first occurrence of relapse or progression
Time frame: Up to 4 years
Progression-free Survival (PFS)
The time from entry to the study (enrollment date for Part 1 and randomization date for Part 2) to the first occurrence of disease progression or death from any cause
Time frame: Up to 4 years
Overall Survival (OS)
The time from entry to the study (enrollment date for Part 1 and randomization date for Part 2) to death from any cause
Time frame: Up to 4 years
Pharmacokinetics - Cmax for CC-220
Maximum plasma concentration of drug
Time frame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days)
Pharmacokinetics - Ctrough for CC-220
Minimum or trough concentration
Time frame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
Pharmacokinetics - Tmax for CC-220
Time to maximum plasma concentration
Time frame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
Pharmacokinetics - Cmax for CC-99282
Maximum plasma concentration
Time frame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
Pharmacokinetics - Ctrough for CC-99282
Minimum or trough concentration
Time frame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
Pharmacokinetics - Tmax for CC-99282
Time to maximum plasma concentration
Time frame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
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