A Dose Finding and Safety Study of CC-220, Alone and in Combination With an Anti-CD20 Monoclonal Antibody (mAb) in Subjects With Relapsed or Refractory Lymphomas

NCT04464798 | Terminated Phase 1 FDA Drug

• 3 other identifiers: CC-220-NHL-001U1111-1254-17722020-000354-10
• Study Type: interventional
• Target: 62
• Locations: 6 countries
• Sites: 26

Brief Summary

This Phase 1/2, multicenter, open-label study to evaluate CC-220 alone, as well as in combination with an anti-CD20 mAb (rituximab or obinutuzumab) in subjects with relapsed or refractory (R/R) lymphoma. Subjects must have received at least 2 prior lines of therapy, and have at least one measurable lesion according to Lugano 2014 classification. Study will consist of two parts: Part 1 (Dose Escalation) which will be followed by Part 2 (Dose Expansion).

Conditions

Lymphoma

Keywords

Relapsed or Refractory Lymphomas; Lymphomas; CC-220; Anti-CD20; Monoclonal Antibody; Pharmacokinetics; Safety

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  is defined as the dose that satisfies the escalation with overdose control (EWOC) criterion that the posterior probability to have excessive toxicity is less than 25% and has the highest probability of dose-limiting toxicity (DLT) rate being in the target interval (0.16 to 0.33)

  During the First cycle (each cycle is 28 days)

• Recommended Phase 2 Dose (RP2D)

  is defined as the dose that will be selected for dose expansion based on PK/Pd and MTD

  During the first Cycle (each cycle is 28 days)

Secondary Outcomes (12)

• Adverse Events (AEs)

  From first dose to 28 days after last subject discontinues study treatment

• Pharmacokinetics - Cmax

  At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)

• Pharmacokinetics - Ctrough

  At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)

• Pharmacokinetics - AUC(TAU)

  At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)

• Pharmacokinetics - tmax

  At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)

Study Arms (7)

Cohort A- Monotherapy in R/R lymphoma subjects

EXPERIMENTAL

Subjects with Relapsed or Refractory (R/R) lymphoma who have been allocated to Cohort A will receive CC-220 monotherapy (MonoT). Oral CC-220 at dose specified by cohort dose level from Day 1 to 21 of each 28-day cycle, up to PD or a maximum of 24 cycles.

Drug: CC-220

Cohort B- CC-220 and rituximab in R/R B-Cell NHL subjects

EXPERIMENTAL

Subjects with R/R B-cell Non Hodgkin Lymphoma (NHL) who have been allocated to Cohort B will receive CC-220 in combination with rituximab. * Oral CC-220 at dose specified by cohort dose level from Day 1 to 21 of each 28-day cycle up to PD or maximum 24 cycles. * Rituximab will be administered at 375 mg/m2 IV at C1D1 and then on D8, D15, and D22 of C1 and then every 28-day cycle at D1 from C2 to C5, either by SC administration at a dose of 1400 mg or by IV infusion at a dose of 375 mg/m2.

Drug: CC-220; Drug: Rituximab

Cohort C - CC-220 and obinutuzumab in R/R FL or MZL subjects

EXPERIMENTAL

Subjects with R/R FL (Grade 1 to 3a) or MZL who have been allocated to Cohort C will receive CC-220 in combination with obinutuzumab. * Oral CC-220 at dose specified by cohort dose level from Day 1 to 21 of each 28-day cycle, up to PD or a maximum of 12 cycles. * Obinutuzumab will be administered at 1000 mg at C1D1, D8, and D15, and on D1 of every 28-day cycle from C2 to C6.

Drug: CC-220; Drug: Obinutuzumab

Cohort D -CC-220 monotherapy in participants with aggressive B-cell lymphoma and follicular lymphoma

EXPERIMENTAL

Drug: CC-220

Cohort E - CC-220 and rituximab in participants with aggressive B-cell lymphoma

EXPERIMENTAL

Drug: CC-220; Drug: Rituximab

Cohort F - CC-220 and rituximab with follicular lymphoma grade 1-3a

EXPERIMENTAL

Drug: CC-220; Drug: Rituximab

Cohort G - CC-220 plus obinutuzumab in participants with follicular lymphoma grade 1-3a

EXPERIMENTAL

Drug: CC-220; Drug: Obinutuzumab

Interventions

CC-220 DRUG

Oral

Also known as: Iberdomide

Cohort A- Monotherapy in R/R lymphoma subjects; Cohort B- CC-220 and rituximab in R/R B-Cell NHL subjects; Cohort C - CC-220 and obinutuzumab in R/R FL or MZL subjects; Cohort D -CC-220 monotherapy in participants with aggressive B-cell lymphoma and follicular lymphoma; Cohort E - CC-220 and rituximab in participants with aggressive B-cell lymphoma; Cohort F - CC-220 and rituximab with follicular lymphoma grade 1-3a; Cohort G - CC-220 plus obinutuzumab in participants with follicular lymphoma grade 1-3a

Rituximab DRUG

SC and IV infusion

Cohort B- CC-220 and rituximab in R/R B-Cell NHL subjects; Cohort E - CC-220 and rituximab in participants with aggressive B-cell lymphoma; Cohort F - CC-220 and rituximab with follicular lymphoma grade 1-3a

Obinutuzumab DRUG

IV Infusion

Cohort C - CC-220 and obinutuzumab in R/R FL or MZL subjects; Cohort G - CC-220 plus obinutuzumab in participants with follicular lymphoma grade 1-3a

Eligibility Criteria

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

You may qualify if:

• Subjects 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).
• Has histologically confirmed (per local evaluation) diagnosis of lymphoma according to 2016 World Health Organization (WHO) classification including:
• Cohort A: all subtypes including B-cell, T-cell and Natural killer (NK)-cell Non-Hodgkin lymphoma (NHL), and Classical Hodgkin lymphoma (cHL).
• Cohort B: all B-cell NHL.
• Cohort C: FL Grade 1-3a and MZL including extranodal marginal zone lymphoma (ENMZL) of mucosa-associated lymphoid tissue (MALT lymphoma), nodal marginal zone lymphoma (NMZL) and splenic marginal zone lymphoma (SMZL)
• Cohort D: aggressive B-cell lymphoma and FL grade 1-3a
• Cohort E: aggressive B-cell lymphoma including DLBCL NOS, high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements, Grade 3b FL and PMBCL
• Cohorts F and G: FL Grade 1 to 3a
• Relapsed or refractory disease according to the following definitions:
• Aggressive B-cell lymphoma
• Follicular lymphoma (FL) and Marginal zone lymphoma (MZL): following at least 2 prior lines of systemic therapy (being previously exposed to at least 1 anti-CD20 mAb and 1 alkylating agent).
• Mantle cell lymphoma (MCL): following at least 2 prior lines of therapy including at least 1 immunochemotherapy and 1 bruton tyrosine kinase (BTK) inhibitor.
• Peripheral T-cell lymphoma (PTCL): following at least 2 prior lines of therapy OR after 1 prior line of standard therapy and being not eligible for any other approved regimen.
• Classical Hodgkin lymphoma (cHL): following at least 2 prior systemic lines of therapy and previously exposed to brentuximab vedotin and anti-PD1.

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Any significant medical condition, active infection (including severe acute respiratory syndrome coronavirus 2 \[SARS-CoV-2) suspected or confirmed, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Life expectancy ≤ 3 months.
• Diagnosis of lymphoblastic lymphoma.
• Aggressive lymphoma relapse requiring immediate cytoreductive therapy to avoid potential life-threatening consequences (eg, due to tumor location).
• Prior Grade 3 or 4 infusion related reaction with rituximab (for Cohorts B, E and F) or obinutuzumab (for Cohorts C and G).
• Prior therapy with the cereblon-modulating drug CC-99282.
• Chronic systemic immunosuppressive therapy or corticosteroids.
• Prior ASCT ≤ 3 months prior to starting CC-220 or \> 3 months AND with unresolved, Grade \> 1, treatment-related toxicity.
• Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-220 or \> 6 months with unresolved, Grade \> 1, treatment-related toxicity.
• Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab or obinutuzumab.
• Known allergy to thalidomide, pomalidomide or lenalidomide.
• Inability or unwilling to undergo protocol required thromboembolism prophylaxis.
• Major surgery ≤ 2 weeks prior to starting CC-220;

Sponsors & Collaborators

• Celgene: lead

Study Sites (26)

Local Institution - 106

Phoenix, Arizona, 85054, United States

Location

Local Institution - 105

Lake Mary, Florida, 32746, United States

Location

Local Institution - 102

Rochester, Minnesota, 55905, United States

Location

Local Institution - 100

New York, New York, 10065, United States

Location

University of Rochester Cancer Center

Rochester, New York, 14642, United States

Location

Local Institution - 103

Nashville, Tennessee, 37203, United States

Location

Local Institution - 203

Créteil, 94010, France

Location

Local Institution - 200

Lillie Cedex, 59037, France

Location

Local Institution - 201

Montpellier, 34295, France

Location

Local Institution - 202

Nantes, 44093, France

Location

Local Institution - 204

Paris, 75010, France

Location

Local Institution - 205

Pessac, 33604, France

Location

Local Institution - 401

Berlin, 12203, Germany

Location

Local Institution - 402

Leipzig, 4103, Germany

Location

Local Institution - 403

Münster, 48149, Germany

Location

Local Institution - 404

Würzburg, 97080, Germany

Location

Local Institution - 300

Brescia, 25123, Italy

Location

Local Institution - 303

Milan, 20133, Italy

Location

Local Institution - 301

Pavia, 27100, Italy

Location

Local Institution - 302

Verona, 37134, Italy

Location

Local Institution - 502

Seoul, 03722, South Korea

Location

Local Institution - 501

Seoul, 06351, South Korea

Location

Local Institution - 500

Seoul, 5505, South Korea

Location

Local Institution - 600

Niaosong District Kaohsiung City, 83301, Taiwan

Location

Local Institution - 601

Taoyuan, 33305, Taiwan

Location

Local Institution - 602

Taoyuan, 40447, Taiwan

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma; Recurrence

Interventions

iberdomide; Rituximab; obinutuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: July 6, 2020
• First Posted: July 9, 2020
• Study Start: November 11, 2020
• Primary Completion: January 31, 2023
• Study Completion: January 9, 2025
• Last Updated: April 29, 2025

Record last verified: 2025-04

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

DE (4); US (6); FR (6); IT (4); KR (3); TW (3)