Study to Evaluate Tolerability of Iberdomide (CC-220) in Combination With Polatuzumab Vedotin Plus Rituximab or Tafasitamab or Rituximab Plus Chemotherapy in B-cell Lymphoma

NCT ID: NCT04882163

Last Updated: 2021-10-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1/PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-10

Study Completion Date

2029-04-07

Brief Summary

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This is a Phase 1b/2 randomized study of Iberdomide (CC-220) added to 3 different combination regimens (polatuzumab vedotin plus rituximab (Cohort A), tafasitamab (Cohort B), rituximab plus gemcitabine and platinum-based chemotherapy (Cohort C)) for participants with relapsed or refractory aggressive B-cell lymphoma (R/R a-BCL). All 3 cohorts will be open for enrollment at study start. Part 1 (dose escalation) will be followed by Part 2 (dose expansion), in which participants will be randomized to one of three cohorts, with CC-220 at the recommended Phase 2 Dose in combination with the Cohorts A, B and C treatment that is compared to their individual standard of care regimen.

Detailed Description

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Conditions

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Lymphoma, B-Cell

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CC-220 + Polatuzumab vedotin + rituximab- Cohort A

Subjects with Relapsed or refractory (R/R) Aggressive B-cell lymphoma (a-BCL) will receive CC-220 at a dose specified by cohort dose level in combination with polatuzumab vedotin plus rituximab.

Group Type EXPERIMENTAL

CC-220

Intervention Type DRUG

CC-220

Polatuzumab vedotin

Intervention Type DRUG

Polatuzumab vedotin

Rituximab

Intervention Type DRUG

Rituximab

CC-220 + Tafasitamab- Cohort B

Subjects with R/R a-BCL will receive CC-220 at a dose specified by cohort dose level in combination with tafasitamab.

Group Type EXPERIMENTAL

CC-220

Intervention Type DRUG

CC-220

Tafasitamab

Intervention Type DRUG

Tafasitamab

CC-220 + Rituximab + Chemo (Cohort C)

Subjects with R/R a-BCL will receive CC-220 at a dose specified by cohort dose level in combination with rituximab plus chemotherapy (Gemcitabine, cisplatin, dexamethasone).

Group Type EXPERIMENTAL

CC-220

Intervention Type DRUG

CC-220

Rituximab

Intervention Type DRUG

Rituximab

Gemcitabine

Intervention Type DRUG

Gemcitabine

Cisplatin

Intervention Type DRUG

Cisplatin

Dexamethasone

Intervention Type DRUG

Dexamethasone

CC-220 + Pola + Ritux vs Pola + Benda + Ritux (Cohort D)

Subjects will be randomized to receive either CC-220 + Pola (polatuzumab vedotin) + Ritux (rituximab) or polatuzumab vedotin + bendamustine + rituximab in 21-day treatment cycles. CC-220 will be given at the RP2D declared in Part 1 of this study. Polatuzumab vedotin and rituximab will be administered at the same levels as in part 1. Bendamustine will be given to subjects randomized in the control arm at a dose of 90 mg/m2 IV on Days 1 and 2 of each of the first 6 cycles.

Group Type EXPERIMENTAL

CC-220

Intervention Type DRUG

CC-220

Polatuzumab vedotin

Intervention Type DRUG

Polatuzumab vedotin

Rituximab

Intervention Type DRUG

Rituximab

Bendamustine

Intervention Type DRUG

Bendamustine

CC-220 + tafasitamab vs Lenalidomide + Tafasitamab- Cohort E

Subjects will be randomized to receive either CC-220 + tafasitamab or lenalidomide + tafasitamab in 28-day treatment cycles. CC-220 will be given at the RP2D declared in Part 1 of this study and the tafasitamab will be at the same levels as in Part 1. Lenalidomide will be administered to subjects randomized in the control arm at a dose of 25 mg/day orally, for 21 days out of 28, for up to 12 cycles.

Group Type EXPERIMENTAL

CC-220

Intervention Type DRUG

CC-220

Tafasitamab

Intervention Type DRUG

Tafasitamab

Lenalidomide

Intervention Type DRUG

Lenalidomide

CC-220 + Rituximab + Chemo vs Rituximab + Chemo (Cohort F)

Subjects will be randomized to receive either CC-220 + rituximab + chemotherapy (Gemcitabine, Cisplatin, Dexamethasone) or rituximab + chemotherapy (Gemcitabine, Cisplatin, Dexamethasone) in 21-day treatment cycles. CC-220 will be administered at the RP2D declared in Part 1 of this study and the combination medicines will be at the same levels as in part 1.

Group Type EXPERIMENTAL

CC-220

Intervention Type DRUG

CC-220

Rituximab

Intervention Type DRUG

Rituximab

Gemcitabine

Intervention Type DRUG

Gemcitabine

Cisplatin

Intervention Type DRUG

Cisplatin

Dexamethasone

Intervention Type DRUG

Dexamethasone

Interventions

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CC-220

CC-220

Intervention Type DRUG

Polatuzumab vedotin

Polatuzumab vedotin

Intervention Type DRUG

Rituximab

Rituximab

Intervention Type DRUG

Tafasitamab

Tafasitamab

Intervention Type DRUG

Gemcitabine

Gemcitabine

Intervention Type DRUG

Cisplatin

Cisplatin

Intervention Type DRUG

Dexamethasone

Dexamethasone

Intervention Type DRUG

Bendamustine

Bendamustine

Intervention Type DRUG

Lenalidomide

Lenalidomide

Intervention Type DRUG

Other Intervention Names

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Iberdomide

Eligibility Criteria

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Inclusion Criteria

* Participants must satisfy the following criteria to be enrolled in the study:

1. Participant 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, aggressive B-cell lymphoma (a-BCL) according to 2016 WHO classification among the following subtypes:

1. Diffuse large B-cell lymphoma (DLBCL), Not otherwise specified (NOS) including Germinal center B-cell and Activated B-cell types;
2. High-grade B-cell lymphoma, with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements;
3. Primary mediastinal (thymic) large B-cell lymphoma (PMBCL);
4. Primary cutaneous DLBCL-leg type;
5. Anaplastic lymphoma kinase positive (ALK+) large B-cell lymphoma;
6. Epstein Barr virus positive (EBV+) DLBCL, NOS;
7. Grade 3b Follicular lymphoma (FL).
3. Participants must have relapsed or refractory disease after at least 2 prior lines of therapy including Rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP)-like regimen OR after one prior line of standard therapy and being not eligible for autologous stem cell transplant (ASCT); participants previously treated with CAR-T therapy can be enrolled.
4. Participant 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. Participant 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 pegylated granulocyte-colony stimulating factor (peg-G-CSF))
2. Hemoglobin ≥ 8 g/dL
3. Platelets ≥ 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 glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x ULN except in the case of documented liver involvement by lymphoma, where ALT/SGPT and AST/SGOT must be ≤ 5.0 x ULN.
5. Serum total bilirubin ≤ 2.0 mg/dL (34 μmol/L) except in cases of Gilbert syndrome, then ≤ 5.0 mg/dL (86 μmol/L)
6. Estimated serum creatinine clearance of ≥ 50 mL/minute using the modification of diet in renal disease 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 Pregnancy Prevention Plan for Participants in Clinical Trials.
8. A female of childbearing potential (FCBP) must:

a. Have two negative pregnancy tests as verified by the investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy.
9. Male participants must:

1. Practice true abstinence (which must be reviewed on a monthly basis and source documented) 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. Participant has 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.

a. In the case of prior SARS-CoV-2 infection, symptoms must have completely resolved
2. Participant has 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. Participant has any other subtype of lymphoma.
4. Participant has received systemic anti-cancer treatment, CAR-T or any T-cell targeting treatment (approved or investigational) ≤ 5 half-lives or 4 weeks prior to starting CC-220, whichever is shorter.
5. Participant has received prior therapy with a Cereblon-modulating drug (eg, lenalidomide, avadomide) ≤ 4 weeks prior to starting CC-220.
6. Participant has persistent diarrhea or malabsorption ≥ Grade 2 (NCI-CTCAE v5.0), despite medical management.
7. Participant has peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0).
8. Participant is on chronic systemic immunosuppressive therapy or corticosteroids.
9. Participant has impaired cardiac function or clinically significant cardiac disease.
10. Participant had major surgery ≤ 2 weeks prior to starting CC-220.
11. Participant has known seropositivity for or active viral infection with human immunodeficiency virus (HIV).
12. Participant has known chronic active hepatitis B
13. Participant has history of other malignancy, unless being free of the disease for ≥ 3 years prior to starting study drug; exceptions to the ≥ 3-year time limit include history of the following:

1. Localized non-melanoma 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. Participant has current treatment with strong CYP3A4/5 modulators.
15. Participant has known hypersensitivity to any component of planned combination medications in the regimen.
16. Participant has known allergy to thalidomide, pomalidomide, lenalidomide or avadomide.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Site Status

Medizinische Universität Graz

Graz, , Austria

Site Status

Universitätsklinikum St. Pölten

Sankt Pölten, , Austria

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

Hôpital de Jolimont

La Louvière, , Belgium

Site Status

H.-Hartziekenhuis Roeselare-Menen vzw

Roeselare, , Belgium

Site Status

EDOG - Institut Bergonie - PPDS

Bordeaux, , France

Site Status

Hôpital François Mitterand

Dijon, , France

Site Status

Centre Hospitalier Lyon Sud

Lyon, , France

Site Status

EDOG - Institut Claudius Regaud - PPDS

Toulouse, , France

Site Status

Gustave Roussy

Villejuif, , France

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Hospital Universitario Germans Trias i Pujol

Badalona, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Complejo Asistencial Universitario de Salamanca - H. Clinico

Salamanca, , Spain

Site Status

Hospital Universitario Virgen del Rocio - PPDS

Seville, , Spain

Site Status

Taipei Veterans General Hospital

Beitou District, Taipei City, , Taiwan

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, Zhongzheng Dist., , Taiwan

Site Status

Beatson West of Scotland Cancer Centre

Glasgow Scotland, , United Kingdom

Site Status

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Site Status

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Site Status

University Hospital Southampton NHS Foundation Trust - Southampton General Hospital

Southampton, , United Kingdom

Site Status

Countries

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United States Austria Belgium France South Korea Spain Taiwan United Kingdom

Other Identifiers

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2020-005333-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-220-DLBCL-002

Identifier Type: -

Identifier Source: org_study_id

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