This website is intended for healthcare professionals

close-icon

Log In to Bolder Science

or

Don't have an account? Sign Up

close-icon

Please enter your email address.

You will receive a link to create a new password via email.

Log In

close-icon

Create an Account

or
  • 8 characters minimum
  • First character may not be a number
  • Last character may not be a number
close-icon

Welcome and thank you for creating an account!

At Bolder Science, we want your clinical trial search experience to be the best it can be. Complete the following prompts to easily find the trials you are interested in and see trials recruiting near you. You can adjust these selections in your dashboard after creating your account.

Condition Categories

Condition categories are pulled directly from ClinicalTrials.gov. Choose 1 or more condition categories that you are interested in:

Clinical Trials of Interest

When I’m looking for information on clinical trials, I usually am interested in...

Set a default location

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

  • Clinicaltrials.gov identifier

    NCT04884035

  • Recruitment Status

    Recruiting

  • First Posted

    May 12, 2021

  • Last update posted

    December 8, 2021

Study Description

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.

  • Condition or Disease:Lymphoma, B-Cell
  • Intervention/Treatment: Drug: CC-220
    Drug: Rituximab
    Drug: Cyclophosphamide
    Drug: Doxorubicin
    Drug: Vincristine
    Drug: Prednisone
    Drug: CC-99282
  • Phase: Phase 1

Detailed Description

N/A

Study Design

  • Study Type: Interventional
  • Estimated Enrollment: 76 participants
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: 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, Poor Risk (IPI 3 to 5), Aggressive B-cell Lymphoma
  • Actual Study Start Date: September 2021
  • Estimated Primary Completion Date: April 2023
  • Estimated Study Completion Date: February 2026

Arms and interventions

Arm Intervention/treatment
Experimental: Administration of CC-220 with R-CHOP-21
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
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.

Drug: Rituximab
Rituxan 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

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

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

Drug: Vincristine
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

Drug: Prednisone
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
Experimental: Administration of CC-99282 with R-CHOP-21
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
Rituxan 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

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

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

Drug: Vincristine
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

Drug: Prednisone
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

Drug: CC-99282
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.

Outcome Measures

  • Primary Outcome Measures: 1. Maximum Tolerated Dose (MTD) - Part 1 [ Time Frame: During the first two cycles of treatment (each cycle is 21 days) ]
    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
  • 2. Recommended Phase 2 Dose (RP2D) - Part 1 [ Time Frame: During the first two cycles of treatment (each cycle is 21 days) ]
    Defined as the dose that will be selected for dose expansion based on MTD
  • 3. Safety and tolerability of CC-220 and CC-99282 at RP2D - Part 2 [ Time Frame: From the first dose of any IP until 28 days after the last dose of IP ]
    AEs evaluated using NCI CTCAE criteria, v. 5.0, including treatment -emergent adverse events (TEAEs) and laboratory assessments
  • Secondary Outcome Measures: 1. Best overall response rate (ORR) [ Time Frame: Up to 4 years ]
    The proportion of participants with best overall response achieved during the study as either Complete Response or Partial Response before subsequent anti-lymphoma therapy
  • 2. Complete Metabolic Response Rate (CMRR) [ Time Frame: Up to 4 years ]
    The proportion of participants experiencing complete metabolic response (CMR) before receiving any subsequent anti-lymphoma therapy
  • 3. Time to Response (TTR) [ Time Frame: Up to 4 years ]
    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)
  • 4. Duration of Response (DOR) [ Time Frame: Up to 4 years ]
    The time from the earliest date of documented response (≥ PR) to the first occurrence of relapse or progression
  • 5. Progression-free Survival (PFS) [ Time Frame: Up to 4 years ]
    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
  • 6. Overall Survival (OS) [ Time Frame: Up to 4 years ]
    The time from entry to the study (enrollment date for Part 1 and randomization date for Part 2) to death from any cause
  • 7. Incidence of Adverse Events (AEs) [ Time Frame: From enrollment until at least 28 days after completion of study treatment ]
    An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE
  • 8. Pharmacokinetics - Cmax for CC-220 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Maximum plasma concentration of drug
  • 9. Pharmacokinetics - Ctrough for CC-220 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Minimum or trough concentration
  • 10. Pharmacokinetics - AUC for CC-220 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Area under the plasma concentration-time curve
  • 11. Pharmacokinetics - tmax for CC-220 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Time to maximum plasma concentration
  • 12. Pharmacokinetics - t½ for CC-220 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Terminal elimination half-life in plasma
  • 13. Pharmacokinetics - CL/F for CC-220 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Apparent total plasma clearance
  • 14. Pharmacokinetics - V/F for CC-220 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Apparent volume of distribution
  • 15. Pharmacokinetics - Cmax for CC-99282 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Maximum plasma concentration
  • 16. Pharmacokinetics - Ctrough for CC-99282 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Minimum or trough concentration
  • 17. Pharmacokinetics - AUC for CC-99282 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Area under the plasma concentration-time curve
  • 18. Pharmacokinetics - tmax for CC-99282 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Time to maximum plasma concentration
  • 19. Pharmacokinetics - t½ for CC-99282 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Terminal elimination half-life in plasma
  • 20. Pharmacokinetics - CL/F for CC-99282 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Apparent total plasma clearance
  • 21. Pharmacokinetics - V/F for CC-99282 [ Time Frame: At Cycle 1 Day 7 and Cycle 2 Day 7 (each cycle is 21 days) ]
    Apparent volume of distribution

Eligibility Criteria

  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria: 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 poor-risk disease defined as International Prognostic Index (IPI) score ≥ 3 (high-intermediate or high-risk). Participants must have measurable disease defined by at least one FDG-avid lesion for FDGavid 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 syndrome, then ≤ 5.0 mg/dl Estimated serum creatinine clearance of ≥ 50 mL/min All participants must: Have an understanding that the study drug could have a potential teratogenic risk. Agree to follow all requirements defined in the Pregnancy Prevention Program for CC-220 or CC-99282 Pregnancy Prevention Plan for Participants in Clinical trials. Females of childbearing potential (FCBP) must: a. Have two negative pregnancy tests as verified by the investigator prior to starting study therapy. Male participants must: Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study. Exclusion Criteria: 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). 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 scan (MUGA) 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 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 History of other malignancy, unless being free of the disease for ≥ 3 years; exceptions to the ≥ 3-year time limit include history of the following: Localized nonmelanoma skin cancer Carcinoma in situ of the cervix Carcinoma in situ of the breast Incidental histologic finding of prostate cancer (T1a or T1b as per Tumor Node Metastasis [TNM] staging system) or prostate cancer that has been treated with curative intent. Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab. Known hypersensitivity to any component of CHOP regimen. Known allergy to thalidomide, pomalidomide, or lenalidomide.

Contacts and Locations

Contacts

Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com

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

Locations

United States, Arizona
Mayo Clinic - Arizona
Scottsdale

United States, Minnesota
Mayo Clinic - Rochester
Rochester

United States, Texas
MD Anderson Cancer Center
Houston

Australia, South Australia
Royal Adelaide Hospital
Adelaide

Australia, Victoria
Austin Health - Austin Hospital
Heidelberg

Greece
Attikon university General Hospital
Athens

Korea, Republic of
Samsung Medical Center
Seoul

Korea, Republic of
Asan Medical Center
Seoul

Korea, Republic of
Seoul National University Hospital
Seoul

Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
Czestochowa

Poland
Uniwersyteckie Centrum Kliniczne
Gdansk

Poland
MCM Krakow - PRATIA - PPDS
Slomniki

Poland
SP ZOZ Szpital Uniwersytecki w Krakowie
Slomniki

Spain
Hospital Universitari Germans Trias i Pujol ICO Badalona
Barcelona

Spain
Hospital General Universitario Gregorio Marañon
Madrid

Spain
H. Virgen de la Victoria
Málaga

Spain
Universitario de Salamanca - Hospital Clinico
Salamanca

Taiwan
China Medical University Hospital
Taichung

Taiwan
Taichung Veterans General Hospital
Taichung

Taiwan
National Taiwan University Hospital
Taipei

Sponsors and Collaborators

Celgene

Investigators

Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

More Information

  • Responsible Party: Celgene
  • ClinicalTrials.gov Identifier: NCT04884035 History of Changes
  • Other Study ID Numbers: CC-220-DLBCL-001, 2020-005705-71
  • First Posted: May 12, 2021 Key Record Dates
  • Last Update Posted: December 8, 2021
  • Last Verified: December 2021
  • Individual Participant
    Data (IPD) Sharing
    Statement:

  • Plan to Share IPD: Yes
  • Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
  • Supporting Materials: Study Protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF), Clinical Study Report (CSR), Analytic Code
  • Time Frame: See Plan Description
  • Access Criteria: See Plan Description
  • URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Celgene: Iberdomide
    CC-220
    CC-99282
    Phase 1
    B-Cell Lymphoma
  • Additional relevant MeSH terms: Lymphoma
    Lymphoma, B-Cell
    Neoplasms by Histologic Type
    Neoplasms
    Lymphoproliferative Disorders
    Lymphatic Diseases
    Immunoproliferative Disorders
    Immune System Diseases
    Lymphoma, Non-Hodgkin