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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
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. 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. 4. 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). 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'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). 6. Estimated serum creatinine clearance (CrCl) of ≥ 50 mL/min using the modification of diet in renal disease (MDRD) formula. 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. Subjects with a history of progressive multifocal leukoencephalopathy. 8. Chronic systemic immunosuppressive therapy or corticosteroids 9. 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) 10. Major surgery ≤ 2 weeks prior to starting CC-220 or CC-99282; participant must have recovered from any clinically significant effects of recent surgery. 11. Any condition causing inability to swallow tablets. 12. Known seropositivity for or active viral infection with human immunodeficiency virus (HIV) 13. 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 14. 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. 15. Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab or polatuzumab vedotin. 16. Known hypersensitivity to any component of CHOP/CHP regimen. 17. Known allergy to thalidomide, pomalidomide, or lenalidomide.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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
    • BMS-986382
  • Drug: Rituximab
    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
  • 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
    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
  • 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.
    Other names:
    • BMS-986369
Experimental
Administration of CC-220 with polatuzumab-R-CHP 		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
    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
    • BMS-986382
  • 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: 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: Polatuzumab vedotin
    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
  • Drug: Rituximab
    Rituximab 375 mg/m2 on Day 1 by intravenous (IV) infusion of a 21-day treatment cycle for up to a total of 6 cycles
Experimental
Administration of CC-99282 with polatuzumab-R-CHP 		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
    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: 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.
    Other names:
    • BMS-986369
  • Drug: Polatuzumab vedotin
    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
  • Drug: Rituximab
    Rituximab 375 mg/m2 on Day 1 by intravenous (IV) infusion of a 21-day treatment cycle for up to a total of 6 cycles

Recruiting Locations

University Of Kansas Medical Center
Kansas City, Kansas 66160
Contact:
Marc Hoffmann, Site 159
913-574-2650

More Details

Status
Recruiting
Sponsor
Celgene

Study Contact

BMS Study Connect Contact Center www.BMSStudyConnect.com
855-907-3286
Clinical.Trials@bms.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.