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

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ClinicalTrials.gov Identifier: NCT04884035
Recruitment Status : Not yet recruiting
First Posted : May 12, 2021
Last Update Posted : June 9, 2021
Sponsor:
Information provided by (Responsible Party):
Celgene

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 Intervention/treatment Phase
Lymphoma, B-Cell Drug: CC-220 Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Drug: CC-99282 Phase 1

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Study Type : Interventional  (Clinical Trial)
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
Estimated Study Start Date : August 12, 2021
Estimated Primary Completion Date : February 10, 2023
Estimated Study Completion Date : March 16, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

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.
Other Name: Iberdomide

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
Other Name: Prednisolone

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
Other Name: Prednisolone

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.




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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

    1. Is ≥ 18 years of age at the time of signing the informed consent form (ICF).
    2. Participant has histologically confirmed (per local evaluation) diagnosis of de novo, previously untreated, a-BCL according to 2016 WHO classification.
    3. Participant has poor-risk disease defined as International Prognostic Index (IPI) score ≥ 3 (high-intermediate or high-risk).
    4. 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).
    5. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
    6. Participants must have the following laboratory values:

      1. 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)
      2. Hemoglobin (Hb) ≥ 8 g/dL
      3. 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
      4. 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.
      5. Serum total bilirubin ≤ 2.0 mg/dL except in cases of Gilbert syndrome, then ≤ 5.0 mg/dl
      6. Estimated serum creatinine clearance of ≥ 50 mL/min
    7. All participants must:

      1. Have an understanding that the study drug could have a potential teratogenic risk.
      2. 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.
    8. Females of childbearing potential (FCBP) must:

      a. Have two negative pregnancy tests as verified by the investigator prior to starting study therapy.

    9. Male participants must:

      1. 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:

    1. 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.
    2. Any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study.
    3. Any other subtype of lymphoma.
    4. Documented or suspected CNS involvement by lymphoma.
    5. Persistent diarrhea or malabsorption ≥ Grade 2 (NCI CTCAE v5.0), despite medical management.
    6. Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0).
    7. Chronic systemic immunosuppressive therapy or corticosteroids
    8. 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)

    9. Major surgery ≤ 2 weeks prior to starting CC-220 or CC-99282; participant must have recovered from any clinically significant effects of recent surgery.
    10. Any condition causing inability to swallow tablets.
    11. Known seropositivity for or active viral infection with human immunodeficiency virus (HIV)
    12. 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
    13. 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:

      1. Localized nonmelanoma skin cancer
      2. Carcinoma in situ of the cervix
      3. Carcinoma in situ of the breast
      4. 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.
    14. Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab.
    15. Known hypersensitivity to any component of CHOP regimen.
    16. Known allergy to thalidomide, pomalidomide, or lenalidomide.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04884035


Contacts
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Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@bms.com

Locations
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United States, Arizona
Mayo Clinic - Arizona
Scottsdale, Arizona, United States, 85259
United States, Minnesota
Mayo Clinic - Rochester
Rochester, Minnesota, United States, 55905
United States, Missouri
Mercy Clinic Springfield
Springfield, Missouri, United States, 65804
United States, Nebraska
University of Nebraska - Fred and Pamela Buffet Center
Omaha, Nebraska, United States, 68198
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77003
Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of, 06351
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Seoul National University Hospital
Seoul, Korea, Republic of, 3080
Spain
Hospital Universitari Germans Trias i Pujol ICO Badalona
Barcelona, Spain, 08916
H. Virgen de la Victoria
Málaga, Spain, 29010
Universitario de Salamanca - Hospital Clinico
Salamanca, Spain, 37007
Taiwan
China Medical University Hospital
Taichung, Taiwan, 404332
Taichung Veterans General Hospital
Taichung, Taiwan, 407219
National Taiwan University Hospital
Taipei, Taiwan, 100229
Sponsors and Collaborators
Celgene
Investigators
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Study Director: Vijaya Kesanakurthy, MD Celgene Corporation
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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT04884035    
Other Study ID Numbers: CC-220-DLBCL-001
2020-005705-71 ( EudraCT Number )
First Posted: May 12, 2021    Key Record Dates
Last Update Posted: June 9, 2021
Last Verified: June 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/

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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:
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Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Prednisone
Prednisolone
Cyclophosphamide
Rituximab
Doxorubicin
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents