A Phase 1b, Open Label, Global, Multicenter, Dose Determination, Randomized Dose Expansion Study to Determine the Maximum Tolerated Dose, Assess the Safety and Tolerability, Pharmacokinetics and Preliminary Efficacy of Iberdomide (CC-220) in Combination With R-CHOP-21 and CC-99282 in Combination With R-CHOP-21 for Subjects With Previously Untreated Aggressive B-cell Lymphoma
Categories (click each to see list of all clinical trials associated with that category): Lymphoma/CLL (ONC)
Current Status: Open
Phase: I
Principal Investigator: Lunning, Matthew
Eligibility: https://clinicaltrials.gov/ct2/show/study/NCT04884035?term=NCT04884035&draw=2&rank=1#eligibility
Summary
Primary
Part 1
To define the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D)of CC-220, also known as BMS986382, in combination with rituximab, cyclophosphamide,doxorubicin, vincristine, and prednisone (R-CHOP) given in 21-day treatment cycles(RCHOP-21) and CC-99282, also known as BMS-986369, in combination with R-CHOP-21in subjects with previously untreated a-BCL.
Part 2
To further evaluate the safety and tolerability associated with CC-220 and/or CC-99282 at theRP2D in combination with R-CHOP-21 in subjects with previously untreated, InternationalPrognostic Index (IPI) 2 to 5, a-BCL.
To define the MTD and/or RP2D of cereblon E3 ligase modulator (CELMoD; CC-220 orCC-99282) in combination with polatuzumab, rituximab, cyclophosphamide, doxorubicin, andprednisone given in 21-day treatment cycles (polatuzumab-R-CHP).
Secondary
Part 1
To determine the safety and tolerability of CC-220 in combination with R-CHOP-21 andCC-99282 in combination with R-CHOP-21 in subjects with previously untreated aBCL.
To characterize the pharmacokinetics (PK) of CC-220 in combination with R-CHOP-21 andCC99282 in combination with R-CHOP21 in subjects with previously untreated a-BCL.
To evaluate the preliminary efficacy of CC-220 in combination with RCHOP-21 andCC-99282 in combination with R-CHOP-21 in subjects with previously untreated aBCL.
Part 2
To evaluate the preliminary efficacy of CC-220 in combination with RCHOP-21 and/orCC-99282 in combination with R-CHOP-21 in subjects with previously untreated, IPI 2 to 5,a-BCL.
To characterize the PK of CC-220 in combination with R-CHOP-21 and/or CC-99282 incombination with RCHOP-21 in subjects with previously untreated, IPI 2 to 5, a-BCL. To determine the safety and tolerability of CC-220 or CC-99282 in combination withpolatuzumab-R-CHP in subjects with previously untreated a-BCL.
To characterize the PK of CC-220 or CC-99282 in combination with polatuzumab-R-CHP insubjects with previously untreated a-BCL.
To evaluate the preliminary efficacy of CC-220 or CC-99282 in combination withpolatuzumab-R-CHP in subjects with previously untreated a-BCL.
Exploratory
To correlate PK with safety profile, clinical activity, and PD biomarkers of CC-220 and CC-99282.
To evaluate the PK of CC-220 metabolite M12, after administration of CC-220 in combination with RCHOP-21 in subjects with previously untreated, a-BCL.
To evaluate the PK of CC1007744 (CC-99282 s R-enantiomer) in subjects with previously untreated, aBCL.
To explore the relationship of dose, exposure, and response to CRBN substrate degradation kinetics in peripheral blood.
To explore the relationship of dose, exposure, and response of CC-220 and CC-99282 to peripheral immune cell populations by immunophenotyping.
To evaluate correlation of protein expression, gene expression or genomic abnormalities in tumor cells to CC-220 and CC-99282 response or relapse.
To evaluate the correlation of baseline and changes in immune cell composition of the tumor microenvironment to CC-220 and CC99282 treatment and response or relapse.
To explore changes in ctDNA levels and mutations and its correlation with radiological and metabolic response.
To assess the impact of SARS-CoV-2 on subjects receiving CC-220 and CC99282 for the treatment of lymphoma and to support health authority requests.
To explore the correlation of biomarkers and efficacy endpoints.