Clincosm LogoSign in Get a demo

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

Sponsor
Celgene (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04884035
Collaborator
(none)
116
Enrollment
27
Locations
2
Arms
52.7
Anticipated Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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 Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
116 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, Aggressive B-cell Lymphoma
Actual Study Start Date :
Sep 15, 2021
Anticipated Primary Completion Date :
Jan 22, 2024
Anticipated Study Completion Date :
Feb 4, 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.
Other Names:
  • 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 Names:
  • 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 Names:
  • 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.

    Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) - Part 1 [During the first cycle 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 [During the first cycle 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 [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) [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) [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) [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) [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) [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) [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) [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 [At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days)]

      Maximum plasma concentration of drug

    9. Pharmacokinetics - Ctrough for CC-220 [At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days]

      Minimum or trough concentration

    10. Pharmacokinetics - AUC (TAU) for CC-220 [At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days]

      Area under the concentration-time curve during a dosing interval of tau

    11. Pharmacokinetics - Tmax for CC-220 [At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days]

      Time to maximum plasma concentration

    12. Pharmacokinetics - CLT/F for CC-220 [At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days]

      Apparent total plasma clearance

    13. Pharmacokinetics - Cmax for CC-99282 [At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days]

      Maximum plasma concentration

    14. Pharmacokinetics - Ctrough for CC-99282 [At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days]

      Minimum or trough concentration

    15. Pharmacokinetics - AUC (TAU) for CC-99282 [At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days]

      Area under the concentration-time curve during a dosing interval of tau

    16. Pharmacokinetics - Tmax for CC-99282 [At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days]

      Time to maximum plasma concentration

    17. Pharmacokinetics - CLT/F for CC-99282 [At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days]

      Apparent total plasma clearance

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 International Prognostic Index (IPI) score 0-5 in Part 1 and IPI 2-5 in Part 2.

    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:

    7. 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)

    8. Hemoglobin (Hb) ≥ 8 g/dL

    9. 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

    10. 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.

    11. Serum total bilirubin ≤ 2.0 mg/dL except in cases of Gilbert syndrome, then ≤ 5.0 mg/dl

    12. Estimated serum creatinine clearance of ≥ 50 mL/min

    13. All participants must:

    14. Have an understanding that the study drug could have a potential teratogenic risk.

    15. 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.

    16. Females of childbearing potential (FCBP) must:

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

    1. Male participants must:

    2. 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:

    1. Left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO)

    1. Major surgery ≤ 2 weeks prior to starting CC-220 or CC-99282; participant must have recovered from any clinically significant effects of recent surgery.

    2. Any condition causing inability to swallow tablets.

    3. Known seropositivity for or active viral infection with human immunodeficiency virus (HIV)

    4. 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

    5. 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:

    6. Localized nonmelanoma skin cancer

    7. Carcinoma in situ of the cervix

    8. Carcinoma in situ of the breast

    9. 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.

    10. Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab.

    11. Known hypersensitivity to any component of CHOP regimen.

    12. Known allergy to thalidomide, pomalidomide, or lenalidomide.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic - Arizona Scottsdale Arizona United States 85259
    2 Mayo Clinic - Jacksonville Jacksonville Florida United States 32224
    3 University of Kansas Medical Center Kansas City Kansas United States 66160
    4 Mayo Clinic - Rochester Rochester Minnesota United States 55905
    5 MD Anderson Cancer Center Houston Texas United States 77003
    6 Royal Adelaide Hospital Adelaide South Australia Australia 5000
    7 Royal Perth Hospital Perth Australia WA 6000
    8 Evangelismos General Hospital of Athens Athens Greece 10676
    9 Laiko General Hospital of Athens Athens Greece 11 527
    10 Attikon university General Hospital Athens Greece 12464
    11 Georgios Papanikolaou General Hospital of Thessaloniki Thessaloniki Greece 57010
    12 Samsung Medical Center Seoul Korea, Republic of 06351
    13 Asan Medical Center Seoul Korea, Republic of 138-736
    14 Seoul National University Hospital Seoul Korea, Republic of 3080
    15 Uniwersyteckie Centrum Kliniczne Gdansk Poland 80-952
    16 MCM Krakow - PRATIA - PPDS Slomniki Poland 32-090
    17 SP ZOZ Szpital Uniwersytecki w Krakowie Slomniki Poland 32-090
    18 Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy Warsaw Poland 02-781
    19 Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu Wroclaw Poland 50-367
    20 Hospital Universitari Germans Trias i Pujol ICO Badalona Barcelona Spain 08916
    21 Hospital General Universitario Gregorio Marañon Madrid Spain 28007
    22 H. Virgen de la Victoria Málaga Spain 29010
    23 Hospital Universitario de Salamanca Salamanca Spain 37007
    24 Local Institution - 200 Salamanca Spain 37007
    25 China Medical University Hospital Taichung Taiwan 404332
    26 Taichung Veterans General Hospital Taichung Taiwan 407219
    27 National Taiwan University Hospital Taipei Taiwan 100229

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT04884035
    Other Study ID Numbers:
    • CC-220-DLBCL-001
    • 2020-005705-71
    First Posted:
    May 12, 2021
    Last Update Posted:
    Jul 7, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Prednisone
    Prednisolone
    Cyclophosphamide
    Rituximab
    Doxorubicin
    Vincristine

    Study Results

    No Results Posted as of Jul 7, 2022