Trial record 1 of 1 for:
CC-220-DLBCL-001
Study of Safety and Efficacy of Iberdomide (CC-220) and CC-99282 Combined With R-CHOP to Treat Lymphoma
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| ClinicalTrials.gov Identifier: NCT04884035 |
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Recruitment Status :
Recruiting
First Posted : May 12, 2021
Last Update Posted : February 21, 2024
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Sponsor:
Celgene
Information provided by (Responsible Party):
Celgene
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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.
| 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 Drug: Polatuzumab vedotin | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 174 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 : | September 15, 2021 |
| Estimated Primary Completion Date : | June 10, 2024 |
| Estimated Study Completion Date : | February 4, 2026 |
| Arm | Intervention/treatment |
|---|---|
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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
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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:
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 Name: Prednisolone |
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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
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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 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.
Other Name: BMS-986369 |
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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
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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:
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 Name: 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 |
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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
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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 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.
Other Name: 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 |
Primary Outcome Measures :
- Maximum Tolerated Dose (MTD) - Part 1 [ Time Frame: During the first 2 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
- Recommended Phase 2 Dose (RP2D) - Part 1 [ Time Frame: 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
- 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
- Maximum Tolerated Dose (MTD) - Part 2A [ Time Frame: During the first cycle of treatment (each cycle is 21 days) ]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
- Recommended Phase 2 Dose (RP2D) - Part 2A [ Time Frame: 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
Secondary Outcome Measures :
- 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
- 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
- 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)
- 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
- 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
- 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
- Pharmacokinetics - Cmax for CC-220 [ Time Frame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days) ]Maximum plasma concentration of drug
- Pharmacokinetics - Ctrough for CC-220 [ Time Frame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days ]Minimum or trough concentration
- Pharmacokinetics - Tmax for CC-220 [ Time Frame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days ]Time to maximum plasma concentration
- Pharmacokinetics - Cmax for CC-99282 [ Time Frame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days ]Maximum plasma concentration
- Pharmacokinetics - Ctrough for CC-99282 [ Time Frame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days ]Minimum or trough concentration
- Pharmacokinetics - Tmax for CC-99282 [ Time Frame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days ]Time to maximum plasma concentration
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.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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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.
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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.
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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.
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Females of childbearing potential (FCBP) must:
a. Have two negative pregnancy tests as verified by the investigator prior to starting study therapy.
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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:
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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
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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
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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 or polatuzumab vedotin.
- Known hypersensitivity to any component of CHOP/CHP regimen.
- 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
| Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com | 855-907-3286 | Clinical.Trials@bms.com | |
| Contact: First line of the email MUST contain the NCT # and Site #. |
Locations
Show 34 study locations
Sponsors and Collaborators
Celgene
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Additional Information:
| 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: | February 21, 2024 |
| Last Verified: | February 2024 |
| 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.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Celgene:
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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 |
Polatuzumab vedotin 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 |