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

NCT04882163 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: CC-220-DLBCL-0022020-005333-32
• Study Type: interventional
• Target: N/A
• Locations: 8 countries
• Sites: 27

Brief Summary

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.

Conditions

Lymphoma, B-Cell

Keywords

CC-220; Phase 1B/2; B-Cell Lymphoma

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD)

  Frequency of dose limiting toxicities (DLT) to define MTD of CC- 220 in combination with polatuzumab vedotin plus rituximab or tafasitamab or rituximab plus chemotherapy in subjects with R/R a-BCL.

  During the First cycle (each cycle is 28 days)

• Recommended Phase 2 Dose (RP2D)

  Frequency of dose limiting toxicities (DLT) to establish the RP2D of CC- 220 in combination with polatuzumab vedotin plus rituximab or tafasitamab or rituximab plus chemotherapy in subjects with R/R a-BCL.

  During the First cycle (each cycle is 28 days)

• Best Overall Response Rate (ORR)

  The proportion of participants with best overall response achieved during the study as either Complete Response or Partial Response before subsequent anti-lymphoma therapy.

  Up to 7 years

Secondary Outcomes (12)

• Incidence of Adverse Events (AEs)

  From enrollment until at least 28 days after last dose of study treatment

• Best ORR- Part 1

  Up to 6 years

• Complete Response Rate (CRR)- Part 2

  Up to 7 years

• Time to Response (TRR)- Part 2

  Up to 7 years

• Duration of Response (DOR)- Part 2

  Up to 7 years

Study Arms (6)

CC-220 + Polatuzumab vedotin + rituximab- Cohort A

EXPERIMENTAL

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.

Drug: CC-220; Drug: Polatuzumab vedotin; Drug: Rituximab

CC-220 + Tafasitamab- Cohort B

EXPERIMENTAL

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

Drug: CC-220; Drug: Tafasitamab

CC-220 + Rituximab + Chemo (Cohort C)

EXPERIMENTAL

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).

Drug: CC-220; Drug: Rituximab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Dexamethasone

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

EXPERIMENTAL

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.

Drug: CC-220; Drug: Polatuzumab vedotin; Drug: Rituximab; Drug: Bendamustine

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

EXPERIMENTAL

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.

Drug: CC-220; Drug: Tafasitamab; Drug: Lenalidomide

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

EXPERIMENTAL

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.

Drug: CC-220; Drug: Rituximab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Dexamethasone

Interventions

CC-220 DRUG

CC-220

Also known as: Iberdomide

CC-220 + Pola + Ritux vs Pola + Benda + Ritux (Cohort D); CC-220 + Polatuzumab vedotin + rituximab- Cohort A; CC-220 + Rituximab + Chemo (Cohort C); CC-220 + Rituximab + Chemo vs Rituximab + Chemo (Cohort F); CC-220 + Tafasitamab- Cohort B; CC-220 + tafasitamab vs Lenalidomide + Tafasitamab- Cohort E

Polatuzumab vedotin DRUG

Polatuzumab vedotin

CC-220 + Pola + Ritux vs Pola + Benda + Ritux (Cohort D); CC-220 + Polatuzumab vedotin + rituximab- Cohort A

Rituximab DRUG

Rituximab

CC-220 + Pola + Ritux vs Pola + Benda + Ritux (Cohort D); CC-220 + Polatuzumab vedotin + rituximab- Cohort A; CC-220 + Rituximab + Chemo (Cohort C); CC-220 + Rituximab + Chemo vs Rituximab + Chemo (Cohort F)

Tafasitamab DRUG

Tafasitamab

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

Gemcitabine DRUG

Gemcitabine

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

Cisplatin DRUG

Cisplatin

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

Dexamethasone DRUG

Dexamethasone

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

Bendamustine DRUG

Bendamustine

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

Lenalidomide DRUG

Lenalidomide

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must satisfy the following criteria to be enrolled in the study:
• Participant is ≥ 18 years of age at the time of signing the informed consent form (ICF).
• Participant has histologically confirmed (per local evaluation) diagnosis of, aggressive B-cell lymphoma (a-BCL) according to 2016 WHO classification among the following subtypes:
• Diffuse large B-cell lymphoma (DLBCL), Not otherwise specified (NOS) including Germinal center B-cell and Activated B-cell types;
• High-grade B-cell lymphoma, with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements;
• Primary mediastinal (thymic) large B-cell lymphoma (PMBCL);
• Primary cutaneous DLBCL-leg type;
• Anaplastic lymphoma kinase positive (ALK+) large B-cell lymphoma;
• Epstein Barr virus positive (EBV+) DLBCL, NOS;
• Grade 3b Follicular lymphoma (FL).
• 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.
• 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).
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Participant 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 pegylated granulocyte-colony stimulating factor (peg-G-CSF))

You may not qualify if:

• The presence of any of the following will exclude a participant from enrollment:
• 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
• 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.
• Participant has any other subtype of lymphoma.
• 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.
• Participant has received prior therapy with a Cereblon-modulating drug (eg, lenalidomide, avadomide) ≤ 4 weeks prior to starting CC-220.
• Participant has persistent diarrhea or malabsorption ≥ Grade 2 (NCI-CTCAE v5.0), despite medical management.
• Participant has peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0).
• Participant is on chronic systemic immunosuppressive therapy or corticosteroids.
• Participant has impaired cardiac function or clinically significant cardiac disease.
• Participant had major surgery ≤ 2 weeks prior to starting CC-220.
• Participant has known seropositivity for or active viral infection with human immunodeficiency virus (HIV).
• Participant has known chronic active hepatitis B
• 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:

Sponsors & Collaborators

• Celgene: lead

Study Sites (27)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Medizinische Universität Graz

Graz, 8036, Austria

Location

Universitätsklinikum St. Pölten

Sankt Pölten, 3100, Austria

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Hôpital de Jolimont

La Louvière, 7100, Belgium

Location

H.-Hartziekenhuis Roeselare-Menen vzw

Roeselare, 8800, Belgium

Location

EDOG - Institut Bergonie - PPDS

Bordeaux, 33076, France

Location

Hôpital François Mitterand

Dijon, 21000, France

Location

Centre Hospitalier Lyon Sud

Lyon, 69373, France

Location

EDOG - Institut Claudius Regaud - PPDS

Toulouse, 31000, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Hospital Universitario Germans Trias i Pujol

Badalona, 8916, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Complejo Asistencial Universitario de Salamanca - H. Clinico

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio - PPDS

Seville, 41013, Spain

Location

Taipei Veterans General Hospital

Beitou District, Taipei City, 11217, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, Zhongzheng Dist., 10002, Taiwan

Location

Beatson West of Scotland Cancer Centre

Glasgow Scotland, G12 OXL, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, Ng5 1PB, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust - Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

iberdomide; polatuzumab vedotin; Rituximab; tafasitamab; Gemcitabine; Cisplatin; Dexamethasone; Bendamustine Hydrochloride; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Isoindoles

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: May 11, 2021
• Study Start: October 10, 2021
• Primary Completion: April 8, 2026
• Study Completion (Estimated): April 7, 2029
• Last Updated: October 5, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

FR (5); KR (3); TW (3); ES (4); GB (4); US (3); AU (2); BE (3)