Study of Safety and Efficacy of Iberdomide (CC-220) and CC-99282 Combined With R-CHOP to Treat Lymphoma
ConditionLymphoma, B-Cell
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorCelgene
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Is ≥ 18 years of age at the time of signing the informed consent form (ICF).
Participant has histologically confirmed (per local evaluation) diagnosis of de novo, previously untreated, a-BCL according to 2016 WHO classification.
Participant has International Prognostic Index (IPI) score 0-5 in Part 1 and IPI 2-5 in Part 2. For the CELMoD and polatuzumab-R-CHP cohort, the subject must also have IPI score 0 to 5 in Part 2A and IPI 2 to 5 in Part 2B.
Participants must have measurable disease defined by at least one FDG-avid lesion for FDG-avid subtype and one bi-dimensionally measurable (> 1.5 cm in longest diameter) disease by computed tomography (CT) or magnetic resonance imaging (MRI), as defined by the Lugano classification (Cheson, 2014).
Disqualifiers
Any significant medical condition, active infection (including SARS-CoV-2 suspected or confirmed), laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study.
Any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study.
Any other subtype of lymphoma.
Documented or suspected CNS involvement by lymphoma.
Trial design
Design model
Parallel
Treatments tested in this trial
CC-220
DrugCC-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
DrugRituximab 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
DrugCyclophosphamide 750mg/m2 on Day 1 by IV infusion of a 21-day treatment cycle for up to a total of 6 cycles
Doxorubicin
DrugDoxorubicin 50 mg/m2 IV infusion on Day 1 of a 21-day treatment cycle for up to a total of 6 cycles
Vincristine
DrugVincristine 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
DrugPrednisone 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
DrugCC-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
DrugPolatuzumab 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
DrugRituximab 375 mg/m2 on Day 1 by intravenous (IV) infusion of a 21-day treatment cycle for up to a total of 6 cycles
Treatment groups
224 Participants
are divided into 4 treatment groupsGroup A: Administration of CC-220 with R-CHOP-21Experimental treatment 6 interventions
Group B: Administration of CC-99282 with R-CHOP-21Experimental treatment 6 interventions
Group C: Administration of CC-220 with polatuzumab-R-CHPExperimental treatment 6 interventions
Group D: Administration of CC-99282 with polatuzumab-R-CHPExperimental treatment 6 interventions
Trial outcomes
Primary outcomes
1
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)2
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)3
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 IP4
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)Secondary outcomes
1
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 years2
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 years3
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 years4
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 Source ClinicalTrials.gov