A Study of Ibrutinib + Obinutuzumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

NCT02537613 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 15-283
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 4

Brief Summary

This research study is evaluating a combination of two drugs, ibrutinib and obinutuzumab, as a possible treatment for Chronic Lymphocytic Leukemia (CLL).

Conditions

Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

  To assess the safety of 3 different dosing regimens of ibrutinib plus obinutuzumab in patients with relapsed/refractory CLL

  Baseline to 6 Months

Secondary Outcomes (7)

• Overall Response Rate

  6 Months

• Partial Response Rate

  6 Months

• Complete Response Rate

  6 Months

• Minimal residual disease (MRD) status in the bone marrow and blood

  6 Months

• Duration of Response

  2 Years

Study Arms (3)

Arm A- obinutuzumab -> ibrutinib

EXPERIMENTAL

Participants enrolled in Arm A will receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6. Participants will begin to take ibrutinib daily starting cycle 2 and will continue with daily ibrutinib until the end of treatment.

Drug: Obinutuzumab; Drug: Ibrutinib

Arm B- ibrutinib -> obinutuzumab

EXPERIMENTAL

Participants enrolled in Arm B will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. Participants will begin to receive obinutuzumab weekly starting cycle 2, and will receive obinutuzumab monthly during cycles 3-7

Drug: Obinutuzumab; Drug: Ibrutinib

Arm C- obinutuzumab/ibrutinib

EXPERIMENTAL

Participants enrolled in Arm C will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. At the same time, participants will begin to receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6.

Drug: Obinutuzumab; Drug: Ibrutinib

Interventions

Obinutuzumab DRUG

Obinutuzumab given weekly during cycle 1, then monthly during cycles 2-6

Also known as: Gazyva, GA-101

Arm A- obinutuzumab -> ibrutinib; Arm B- ibrutinib -> obinutuzumab; Arm C- obinutuzumab/ibrutinib

Ibrutinib DRUG

Ibrutinib given once daily by mouth

Also known as: Imbruvica

Arm A- obinutuzumab -> ibrutinib; Arm B- ibrutinib -> obinutuzumab; Arm C- obinutuzumab/ibrutinib

Eligibility Criteria

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

You may qualify if:

• Must have a confirmed diagnosis of Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma as per IW-CLL 2008 criteria and require therapy based on meeting at least one of the following criteria:
• Evidence of progressive marrow failure with anemia (hemoglobin \<11.0 g/L) and/or thrombocytopenia (platelets \<100 x 10\^9/L)
• Massive (≥6 cm below the left costal margin), progressive, or symptomatic splenomegaly
• Massive nodes (at least 10 cm longest diameter), progressive, or symptomatic lymphadenopathy
• Progressive lymphocytosis with an increase of more than 50% over a 2-month period or LDT of \<6 months.
• Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids
• Constitutional symptoms, defined as 1 or more of the following:
• unintentional weight loss \>10% within 6 months prior to screening
• significant fatigue (inability to work or perform usual activities) fevers \>100.5° F or 38.0° C for 2 or more weeks prior to screening without evidence of infection
• night sweats for more than 1 month prior to screening without evidence of infection
• Relapsed after or refractory to at least one prior Chronic Lymphocytic Leukemia-directed therapy
• Age greater than or equal to 18 years
• ECOG Performance Status \<2
• Heme criteria at screening, unless significant bone marrow involvement of Chronic Lymphocytic Leukemia confirmed on biopsy:
• Absolute Neutrophil Count (ANC) ≥500 cells/mm3 (0.5 x 10\^9/L). Growth factor allowed to achieve

You may not qualify if:

• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• Prior treatment with either obinutuzumab or ibrutinib
• History of other malignancies, except:
• Malignancy treated with curative intent and with no known active disease present for ≥3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.
• Low-risk prostate cancer on active surveillance
• Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration of \>20 mg/day of prednisone) within 28 days of the first dose of study drug.
• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
• Recent infection requiring systemic treatment that was completed ≤7 days before the first dose of study drug.
• Known bleeding disorders or hemophilia.
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• Known history of HIV or active hepatitis C virus (HCV) or hepatitis B virus (HBV).
• Any uncontrolled active systemic infection.
• Major surgery within 4 weeks of first dose of study drug.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Genentech, Inc.: collaborator

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Rochester Wilmot Cancer Inst.

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

obinutuzumab; ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Matthew Davids, MD, MMSc

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: September 1, 2015
• Study Start: December 1, 2015
• Primary Completion: March 1, 2020
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)