RECRUITING

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

Conditions

Lymphoma, B-Cell Iberdomide CC-220 CC-99282 Phase 1 B-Cell Lymphoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2021-09-15

Study Completion:2026-02-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04884035

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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: 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.	* 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: 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.

Inclusion Criteria

Exclusion 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:
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.

* 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:
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.

Contacts and Locations

Study Contact

BMS Study Connect Contact Center www.BMSStudyConnect.com

CONTACT

855-907-3286

Clinical.Trials@bms.com

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

CONTACT

Principal Investigator

Bristol-Myers Squibb

STUDY_DIRECTOR

Bristol-Myers Squibb

Study Locations (Sites)

Mayo Clinic - Arizona

Scottsdale, Arizona, 85259

United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224

United States

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, 32224

United States

University Of Kansas Medical Center

Kansas City, Kansas, 66160

United States

Mayo Clinic - Rochester

Rochester, Minnesota, 55905-0001

United States

University of Nebraska - Fred and Pamela Buffet Center

Omaha, Nebraska, 68198

United States

Roswell Park Cancer Institute

Buffalo, New York, 14263

United States

MD Anderson Cancer Center

Houston, Texas, 77003

United States

Collaborators and Investigators

Sponsor: Celgene

Bristol-Myers Squibb, STUDY_DIRECTOR, Bristol-Myers Squibb

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-09-15

Study Completion Date2026-02-04

Study Record Updates

Study Start Date2021-09-15

Study Completion Date2026-02-04

Terms related to this study

Keywords Provided by Researchers

Iberdomide
CC-220
CC-99282
Phase 1
B-Cell Lymphoma

Additional Relevant MeSH Terms

Lymphoma, B-Cell