A Phase 1b Open-label Study to Evaluate the Safety and Efficacy of CC-122 With Obinutuzumab (GA101) in Relapsed/Refractory DLBCL and iNHL.

NCT02417285 | Completed Phase 1

• 1 other identifier: CC-122-NHL-001
• Study Type: interventional
• Target: 75
• Locations: 3 countries
• Sites: 8

Brief Summary

CC-122-NHL-001 study is a multicenter, open-label, phase Ib study with dose escalation and expansion parts. It evaluates the safety, tolerability and clinical pharmacokinetics of CC-122 in combination with obinutuzumab (GA101). The study is also assessing the preliminary efficacy of the combination as well as pharmacodynamic and tumor biomarkers as exploratory objectives. In the dose escalation part, the safety and tolerability of increasing doses of CC-122 administered with a fixed dose of obinutuzumab will be administered to identify the maximum tolerated dose. In the dose expansion part, more patients will be enrolled at a CC-122 dose selected from the escalation part of the study in combination with fixed dose obinutuzumab to further study safety and efficacy.

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin

Keywords

Non-Hodgkin's Lymphoma; Diffused Large B-Cell Lymphoma; Phase 1B; Open-Label; Safety and Efficacy; CC-122; Obinutuzumab; GA101; Relapsed; Refractory

Outcome Measures

Primary Outcomes (1)

• Adverse Events (AEs)

  Number of participants with adverse events

  Approximately 6 years

Secondary Outcomes (9)

• Tumor Response

  Approximately 6 years

• Response Duration

  Approximately 6 years

• Progression-free Survival (PFS)

  Approximately 6 years

• Pharmacokinetics - Cmax

  up to 8 months

• Pharmacokinetics AUC

  Up to 8 months

Study Arms (1)

CC-122 in combination with Obinutuzumab

EXPERIMENTAL

CC-122 will be administered orally QD starting on Day 1 for 5 consecutive days followed by 2 days off study drug every 7 days (5/7-day schedule) in each 28-day cycle in combination with Obinutuzumab administered as an intravenous (IV) infusion at a dose of 1000 mg on Days 2, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 through 8.

Drug: Obinutuzumab; Drug: CC-122

Interventions

Obinutuzumab DRUG

1000 mg administered IV on Days 2, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 though 8.

Also known as: GA-101

CC-122 in combination with Obinutuzumab

CC-122 DRUG

CC-122 1mg, 2mg, 3mg, 4mg or 5mg administered orally once daily on a 5/7-day schedule in each 28-day cycle. In addition, subjects will be enrolled on the CC-122 formulated capsule (F6) and evaluated for safety and tolerability in combination with GA101 (Obinituzumab) in a separate cohort. The CC-122 dose will be escalated until the MTD is established on the CC-122 formulated capsule (F6) in combination with GA101 (Obinituzumab).

CC-122 in combination with Obinutuzumab

Eligibility Criteria

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

You may qualify if:

• Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
• ≥ 18 years of age or older at the time of signing the informed consent document.
• Entry Criteria Specific for Dose-Escalation Phase (Part A)
• Subjects with CD20 positive, histologically or cytologically-confirmed, diffuse large B-cell lymphoma (DLBCL)(including transformed low grade lymphoma) who have relapsed or refractory disease following at least two prior standard treatment regimens (eg, R-CHOP or similar first-lineregimen and at least one second-line salvage regimen) and/or autologous stem cell transplant (ASCT) in chemotherapy-sensitive patients, with the following ASCT
• EXCEPTIONS:
• Subjects in the pre-ASCT setting with poor prognosis, defined as primary refractory disease, that have relapsed within 12 months following first-line treatment; "double-hit" lymphomas with Bcl-2/Myc gene rearrangements or, overexpression or high IPI score (2,3) at relapse.
• Subjects refusing ASCT or for whom ASCT is not appropriate based on the Investigator's judgment.
• Entry Criteria Specific for Dose-Expansion Phase (Part B)
• Subjects with CD20 positive, histologically confirmed (by WHO 2008 classification \[Jaffe, 2009\]), FL (Grade 1, 2, or 3a) who have relapsed or refractory disease following at least one prior standard systemic treatment regimen including systemic chemo-, immune-, or chemoimmunotherapy.
• Systemic therapy includes treatments such as rituximab monotherapy, chemotherapy given with or without rituximab, radio-immunoconjugates such as 90Y-ibritumomab tiuxetan and 1311-tositumomab. Systemic therapy does not include, for example, H. pylori eradication or antibiotic treatment.
• Lenalidomide naïve
• Relapsed or refractory follicular lymphoma (Grade 1, 2, or 3a) following at least one prior standard systemic treatment regimen including systemic chemo-, immune-, or chemoimmunotherapy with no prior exposure to lenalidomide (FL-1 cohort)
• Lenalidomide exposed
• Relapsed or refractory follicular lymphoma (Grade 1, 2, or 3a) previously treated with at least two cycles of lenalidomide-containing regimen (FL-2 cohort), either as a single agent or in combination, and experienced outcomes to the lenalidomide treatment as follows:
• Early relapse after lenalidomide treatment: Subjects with relapse within one year of last dose of lenalidomide (or a lenalidomide-containing regimen) following initial response of Complete Response (CR) to lenalidomide (or a lenalidomide-containing regimen) Early progression after lenalidomide treatment: Subjects with Progressive Disease (PD) within one year of last dose of lenalidomide (or lenalidomide-containing regimen) following initial response of partial response (PR) to lenalidomide (or a lenalidomide-containing regimen) Disease refractory to lenalidomide: Subjects with best response of stable disease (SD) or PD while on lenalidomide (or lenalidomide-containing regimen) without any documented response of PR or better during treatment with lenalidomide (or a lenalidomide-containing regimen) Lenalidomide or lenalidomide - containing regimen does not need to be the immediate prior regimen received by the subject to be eligible for entry.

You may not qualify if:

• Any significant medical condition, 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.
• Any condition that confounds the ability to interpret data from the study.
• Symptomatic central nervous system involvement.
• Any history of progressive multifocal leukoencephalopathy (PML).
• Known symptomatic acute or chronic pancreatitis.
• Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management.
• Peripheral neuropathy ≥ NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade 2
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• LVEF (left ventricular ejection fraction) \< 45% as determined by MUGA (multi-gated acquisition scan) or ECHO (echocardiogram).
• Complete left bundle branch or bifascicular block.
• Congenital long QT syndrome.
• Persistent or clinically meaningful ventricular arrhythmias.
• QTcF \> 460 msec on Screening ECG (electrocardiogram) (mean of triplicate recordings as assessed by central read).
• Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting study drugs.

Sponsors & Collaborators

• Celgene: lead

Study Sites (8)

Local Institution - 105

Borddeaux Cedex, 33076, France

Location

Local Institution - 102

Marseille, 13273, France

Location

Local Institution - 103

Pierre-Bénite, 69495, France

Location

Local Institution - 101

Villejuif, 94805, France

Location

Local Institution - 301

Bologna, 40138, Italy

Location

Local Institution - 302

Torino, 10126, Italy

Location

Local Institution - 201

Amsterdam, 1105, Netherlands

Location

Local Institution - 202

Rotterdam, 3075 EA, Netherlands

Location

Related Publications (1)

• Michot JM, Bouabdallah R, Vitolo U, Doorduijn JK, Salles G, Chiappella A, Zinzani PL, Bijou F, Kersten MJ, Sarmiento R, Mosulen S, Mendez C, Uttamsingh S, Pourdehnad M, Hege K, Chen T, Klein C, Hagner PR, Nikolova Z, Ribrag V. Avadomide plus obinutuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (CC-122-NHL-001): a multicentre, dose escalation and expansion phase 1 study. Lancet Haematol. 2020 Sep;7(9):e649-e659. doi: 10.1016/S2352-3026(20)30208-8. Epub 2020 Aug 3.

  PMID: 32758434 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Recurrence

Interventions

obinutuzumab; 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma; 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

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2015
• First Posted: April 15, 2015
• Study Start: May 22, 2015
• Primary Completion: May 27, 2019
• Study Completion: September 28, 2023
• Last Updated: October 23, 2023

Record last verified: 2023-10

Locations

FR (4); IT (2); NL (2)