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

January 5, 2024 updated by: Matthew S. Davids, MD, Dana-Farber Cancer Institute

A Phase Ib Study of Ibrutinib in Combination With Obinutuzumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the best order of administration of these two drugs. "Investigational" means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has approved ibrutinib and obinutuzumab individually for the treatment of patients with Chronic Lymphocytic Leukemia, your type of cancer. However, the FDA has not approved the combination of these two drugs as a treatment for any disease.

Ibrutinib is a type of drug called a kinase inhibitor. It is believed to block a type of protein called a kinase that helps leukemia cells live and grow. By blocking this, it is possible that the study drug will kill cancer cells or stop them from growing.

Obinutuzumab is a type of drug called a monoclonal antibody. It is believed to attach to a protein called CD20 on the outside of a Chronic Lymphocytic Leukemia cell. By attaching to the cell, the antibody can cause the Chronic Lymphocytic Leukemia cell to die.

In this research study, the investigators are assessing the safety of various dosing regimens of ibrutinib and obinutuzumab. The investigators are trying to determine whether it is better to give one drug before the other or if they can be started at the same time.

Study Type

Interventional

Enrollment (Actual)

54

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester Wilmot Cancer Inst.
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  • 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
    • Platelet count ≥25,000 cells/mm3 (25 x 10^9/L) independent of transfusion within 7 days of screening
  • Adequate hepatic function defined as: AST and ALT ≤ 4.0 x upper limit of normal (ULN), bilirubin ≤2.0 x upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's syndrome)
  • Adequate renal function defined by serum creatinine <2.0 x upper limit of normal (ULN) unless due to biopsy proven Chronic Lymphocytic Leukemia kidney infiltration
  • Women of child-bearing potential and men must agree to use adequate contraception
  • Patients who have undergone prior allo transplant are eligible provided that their transplant day 0 is > 6 months from their first dose of study drug

Exclusion Criteria:

  • 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.
  • Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 CHF as defined by the NYHA Functional Classification; or a history of Myocardial Infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
  • Lactating or pregnant.
  • Patients receiving any other study agents
  • Patients with known Central Nervous System involvement
  • Baseline QT Interval Corrected by the Fridericia Correction Formula (QTcF) >480 ms unless Left Bundle Branch Block
  • Patients who require warfarin or other vitamin K antagonists for anticoagulation
  • Concurrent administration of strong inhibitors or inducers of CYP3A

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A- obinutuzumab -> ibrutinib
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
Obinutuzumab given weekly during cycle 1, then monthly during cycles 2-6
Other Names:
  • Gazyva
  • GA-101
Drug: Ibrutinib
Ibrutinib given once daily by mouth
Other Names:
  • Imbruvica
Experimental: Arm B- ibrutinib -> obinutuzumab
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
Obinutuzumab given weekly during cycle 1, then monthly during cycles 2-6
Other Names:
  • Gazyva
  • GA-101
Drug: Ibrutinib
Ibrutinib given once daily by mouth
Other Names:
  • Imbruvica
Experimental: Arm C- obinutuzumab/ibrutinib
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
Obinutuzumab given weekly during cycle 1, then monthly during cycles 2-6
Other Names:
  • Gazyva
  • GA-101
Drug: Ibrutinib
Ibrutinib given once daily by mouth
Other Names:
  • Imbruvica

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
Time Frame: Baseline to 6 Months
To assess the safety of 3 different dosing regimens of ibrutinib plus obinutuzumab in patients with relapsed/refractory CLL
Baseline to 6 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: 6 Months
To assess the efficacy of ibrutinib plus obinutuzumab in patients with relapsed/refractory CLL as measured by:
6 Months
Partial Response Rate
Time Frame: 6 Months
To assess the efficacy of ibrutinib plus obinutuzumab in patients with relapsed/refractory CLL as measured by:
6 Months
Complete Response Rate
Time Frame: 6 Months
To assess the efficacy of ibrutinib plus obinutuzumab in patients with relapsed/refractory CLL as measured by:
6 Months
Minimal residual disease (MRD) status in the bone marrow and blood
Time Frame: 6 Months
To assess the efficacy of ibrutinib plus obinutuzumab in patients with relapsed/refractory CLL as measured by:
6 Months
Duration of Response
Time Frame: 2 Years
To assess the efficacy of ibrutinib plus obinutuzumab in patients with relapsed/refractory CLL as measured by:
2 Years
Progression Free Survival
Time Frame: 2 Years
To assess the efficacy of ibrutinib plus obinutuzumab in patients with relapsed/refractory CLL as measured by:
2 Years
Overall Response Rate
Time Frame: 2 Years
To assess the efficacy of ibrutinib plus obinutuzumab in patients with relapsed/refractory CLL as measured by:
2 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Collaborators

Genentech, Inc.

Investigators

  • Principal Investigator: Matthew Davids, MD, MMSc, Dana-Farber Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2015

Primary Completion (Actual)

March 1, 2020

Study Completion (Estimated)

January 1, 2029

Study Registration Dates

First Submitted

August 27, 2015

First Submitted That Met QC Criteria

August 28, 2015

First Posted (Estimated)

September 1, 2015

Study Record Updates

Last Update Posted (Actual)

January 9, 2024

Last Update Submitted That Met QC Criteria

January 5, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-283

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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