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

This study is currently recruiting participants.
Verified July 2017 by Matthew S. Davids, MD, Dana-Farber Cancer Institute
Sponsor:
ClinicalTrials.gov Identifier:
NCT02537613
First Posted: September 1, 2015
Last Update Posted: July 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Matthew S. Davids, MD, Dana-Farber Cancer Institute
  Purpose
This research study is evaluating a combination of two drugs, ibrutinib and obinutuzumab, as a possible treatment for Chronic Lymphocytic Leukemia (CLL).

Condition Intervention Phase
Chronic Lymphocytic Leukemia Drug: Obinutuzumab Drug: Ibrutinib Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib Study of Ibrutinib in Combination With Obinutuzumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Matthew S. Davids, MD, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 [ Time Frame: Baseline to 6 Months ]

Secondary Outcome Measures:
  • Overall Response Rate [ Time Frame: 6 Months ]
  • Partial Response Rate [ Time Frame: 6 Months ]
  • Complete Response Rate [ Time Frame: 6 Months ]
  • Minimal residual disease (MRD) status in the bone marrow and blood [ Time Frame: 6 Months ]
  • Duration of Response [ Time Frame: 2 Years ]
  • Progression Free Survival [ Time Frame: 2 Years ]
  • Overall Response Rate [ Time Frame: 2 Years ]

Estimated Enrollment: 40
Study Start Date: December 2015
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Imbruvica

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 Lymphomcytic 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 Lymphomcytic Leukemia cell. By attaching to the cell, the antibody can cause the Chronic Lymphomcytic 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Must have a confirmed diagnosis of Chronic Lymphomcytic 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 Lymphomcytic 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 Lymphomcytic 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 Lymphomcytic 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02537613


Contacts
Contact: Matthew Davids, MD, MMSc 617-632-6331 matthew_davids@dfci.harvard.edu

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Jeremy Abramson, MD    617-724-4000    jabramson@partners.org   
Principal Investigator: Jeremy Abramson, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Matthew Davids, MD    617-632-6331    matthew_davids@dfci.harvard.edu   
Principal Investigator: Matthew Davids, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Genentech, Inc.
Investigators
Principal Investigator: Matthew Davids, MD, MMSc Dana-Farber Cancer Institute
  More Information

Responsible Party: Matthew S. Davids, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02537613     History of Changes
Other Study ID Numbers: 15-283
First Submitted: August 27, 2015
First Posted: September 1, 2015
Last Update Posted: July 7, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Matthew S. Davids, MD, Dana-Farber Cancer Institute:
Chronic Lymphocytic Leukemia

Additional relevant MeSH terms:
Obinutuzumab
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents