Study of Safety and Efficacy of Iberdomide (CC-220) and CC-99282 Combined With R-CHOP to Treat Lymphoma

NCT04884035 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: CC-220-DLBCL-0012023-506094-35
• Study Type: interventional
• Target: 224
• Locations: 7 countries
• Sites: 42

Brief Summary

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.

Conditions

Lymphoma, B-Cell

Keywords

Iberdomide; CC-220; CC-99282; Phase 1; B-Cell Lymphoma

Outcome Measures

Primary Outcomes (5)

• 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

  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

  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

  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

  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

  During the first cycle of treatment (each cycle is 21 days)

Secondary Outcomes (12)

• Best overall response rate (ORR)

  Up to 4 years

• Complete Metabolic Response Rate (CMRR)

  Up to 4 years

• Time to Response (TTR)

  Up to 4 years

• Duration of Response (DOR)

  Up to 4 years

• Progression-free Survival (PFS)

  Up to 4 years

Study Arms (4)

Administration of CC-220 with R-CHOP-21

EXPERIMENTAL

CC-220 to be administered orally in combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP-21) for 6 cycles of treatment

Drug: CC-220; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone

Administration of CC-99282 with R-CHOP-21

EXPERIMENTAL

CC-99282 to be administered orally in combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP-21) for 6 cycles of treatment

Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: CC-99282

Administration of CC-220 with polatuzumab-R-CHP

EXPERIMENTAL

CC-220 to be administered orally in combination with Polatuzumab vedotin, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (polatuzumab-R-CHP) for 6 cycles of treatment

Drug: CC-220; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Polatuzumab vedotin; Drug: Rituximab

Administration of CC-99282 with polatuzumab-R-CHP

EXPERIMENTAL

CC-99282 to be administered orally in combination with Polatuzumab vedotin, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (polatuzumab-R-CHP) for 6 cycles of treatment

Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: CC-99282; Drug: Polatuzumab vedotin; Drug: Rituximab

Interventions

CC-220 DRUG

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.

Also known as: Iberdomide, BMS-986382

Administration of CC-220 with R-CHOP-21; Administration of CC-220 with polatuzumab-R-CHP

Cyclophosphamide DRUG

Cyclophosphamide 750mg/m2 on Day 1 by IV infusion of a 21-day treatment cycle for up to a total of 6 cycles

Administration of CC-220 with R-CHOP-21; Administration of CC-220 with polatuzumab-R-CHP; Administration of CC-99282 with R-CHOP-21; Administration of CC-99282 with polatuzumab-R-CHP

Doxorubicin DRUG

Doxorubicin 50 mg/m2 IV infusion on Day 1 of a 21-day treatment cycle for up to a total of 6 cycles

Administration of CC-220 with R-CHOP-21; Administration of CC-220 with polatuzumab-R-CHP; Administration of CC-99282 with R-CHOP-21; Administration of CC-99282 with polatuzumab-R-CHP

Vincristine DRUG

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

Administration of CC-220 with R-CHOP-21; Administration of CC-99282 with R-CHOP-21

Prednisone DRUG

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

Also known as: Prednisolone

Administration of CC-220 with R-CHOP-21; Administration of CC-220 with polatuzumab-R-CHP; Administration of CC-99282 with R-CHOP-21; Administration of CC-99282 with polatuzumab-R-CHP

CC-99282 DRUG

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.

Also known as: BMS-986369

Administration of CC-99282 with R-CHOP-21; Administration of CC-99282 with polatuzumab-R-CHP

Polatuzumab vedotin DRUG

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

Administration of CC-220 with polatuzumab-R-CHP; Administration of CC-99282 with polatuzumab-R-CHP

Rituximab DRUG

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

Administration of CC-220 with R-CHOP-21; Administration of CC-99282 with R-CHOP-21

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must satisfy the following criteria to be enrolled in the study:
• 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).
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Participants must have the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L or ≥ 1.0 x 109/L in case of documented bone marrow involvement (\> 50% or tumor cells), without growth factor support for 7 days (14 days if peg-G-CSF)
• Hemoglobin (Hb) ≥ 8 g/dL
• Platelets (PLT) ≥ 75 x 109/L or ≥ 50 x 109/L in case of documented bone marrow involvement (\>50% or tumor cells), without transfusion for 7 days
• Aspartate aminotransferase / serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase / serum glutamate pyruvic transaminase (ALT/SGPT) ≤ 2.5 x upper limit of normal (ULN). In the case of documented liver involvement by lymphoma, ALT/SGPT and AST/SGOT must be ≤ 5.0 x ULN.
• Serum total bilirubin ≤ 2.0 mg/dL except in cases of Gilbert's syndrome, then ≤ 5.0 mg/dl. Subjects receiving polatuzumab vedotin must have serum total bilirubin \< 1.5 × ULN (26 μmol/L) (corresponding to mild degree as per National Cancer Institute Organ Dysfunction Working Group \[NCI ODWG\] criteria) except in cases of Gilbert's syndrome, then ≤ 3.0 mg/dl (51 μmol/L).
• Estimated serum creatinine clearance (CrCl) of ≥ 50 mL/min using the modification of diet in renal disease (MDRD) formula.
• All participants must:
• Have an understanding that the study drug could have a potential teratogenic risk.

You may not qualify if:

• The presence of any of the following will exclude a participant from enrollment:
• 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.
• Persistent diarrhea or malabsorption ≥ Grade 2 (NCI CTCAE v5.0), despite medical management.
• Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0).
• Subjects with a history of progressive multifocal leukoencephalopathy.
• Chronic systemic immunosuppressive therapy or corticosteroids
• Impaired cardiac function or clinically significant cardiac disease, including any of the following:
• a. Left ventricular ejection fraction (LVEF) \< 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO)
• Major surgery ≤ 2 weeks prior to starting CC-220 or CC-99282; participant must have recovered from any clinically significant effects of recent surgery.
• Any condition causing inability to swallow tablets.
• Known seropositivity for or active viral infection with human immunodeficiency virus (HIV)
• Known chronic active hepatitis B (hepatitis B virus surface antigen \[HBsAg\] positive and/or hepatitis B core antibody \[anti-HBc\] positive with viral DNA positive) or C (positive serology requiring treatment and/or with evidence of liver damage) infection

Sponsors & Collaborators

• Celgene: lead

Study Sites (42)

Local Institution - 162

Birmingham, Alabama, 35233, United States

NOT YET RECRUITING

Mayo Clinic - Arizona

Scottsdale, Arizona, 85259, United States

RECRUITING

Local Institution - 169

Duarte, California, 91010, United States

NOT YET RECRUITING

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

WITHDRAWN

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, 32224, United States

RECRUITING

Local Institution - 161

Marietta, Georgia, 30060, United States

NOT YET RECRUITING

University Of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Cancer Center Of Kansas-Wichita

Wichita, Kansas, 67214, United States

RECRUITING

Mayo Clinic - Rochester

Rochester, Minnesota, 55905-0001, United States

RECRUITING

HealthPartners Cancer Research Center

Saint Louis Park, Minnesota, 55426, United States

RECRUITING

University of Nebraska - Fred and Pamela Buffet Center

Omaha, Nebraska, 68198, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

WITHDRAWN

Local Institution - 170

Charlotte, North Carolina, 28204, United States

NOT YET RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77003, United States

RECRUITING

Local Institution - 168

Murray, Utah, 84107, United States

NOT YET RECRUITING

Local Institution - 171

St. George, Utah, 84790, United States

NOT YET RECRUITING

Local Institution - 501

Adelaide, South Australia, 5000, Australia

COMPLETED

Local Institution - 503

Perth, WA 6000, Australia

COMPLETED

Local Institution - 502

Waratah, NSW, Australia

WITHDRAWN

Evangelismos General Hospital of Athens

Athens, 10676, Greece

RECRUITING

General Hospital of Athens "Laiko"

Athens, 11 527, Greece

RECRUITING

Attikon University General Hospital

Athens, 12464, Greece

RECRUITING

Local Institution - 703

Pátrai, 26500, Greece

WITHDRAWN

Georgios Papanikolaou General Hospital of Thessaloniki

Thessaloniki, 57010, Greece

RECRUITING

AIDPORT Sp. z o.o.

Skórzewo, Greater Poland Voivodeship, 60-185, Poland

RECRUITING

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

RECRUITING

MCM Krakow - PRATIA - PPDS

Krakow, 30-727, Poland

RECRUITING

Local Institution - 0706

Poznan, 60-185, Poland

WITHDRAWN

Local Institution - UNK0706

Poznan, 60-185, Poland

WITHDRAWN

SP ZOZ Szpital Uniwersytecki w Krakowie

Słomniki, 32-090, Poland

RECRUITING

Local Institution - 602

Warsaw, 02-781, Poland

RECRUITING

Local Institution - 604

Wroclaw, 50-367, Poland

COMPLETED

Local Institution - 300

Seoul, 06351, South Korea

COMPLETED

Local Institution - 302

Seoul, 138-736, South Korea

COMPLETED

Local Institution - 301

Seoul, 3080, South Korea

COMPLETED

Hospital Universitari Germans Trias i Pujol ICO Badalona

Barcelona, 08916, Spain

RECRUITING

Local Institution - 204

Madrid, 28028, Spain

WITHDRAWN

H. Virgen de la Victoria

Málaga, 29010, Spain

RECRUITING

Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca

Salamanca, 37007, Spain

RECRUITING

China Medical University Hospital

Taichung, 40447, Taiwan

RECRUITING

Taichung Veterans General Hospital

Taichung, 407, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 100229, Taiwan

RECRUITING

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

iberdomide; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; Prednisolone; polatuzumab vedotin

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Central Study Contacts

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

CONTACT

855-907-3286; Clinical.Trials@bms.com

First line of the email MUST contain NCT # and Site #.

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: May 12, 2021
• Study Start: September 15, 2021
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

US (16); GR (5); AU (3); KR (3); PL (8); ES (4); TW (3)