Clinical Trial - NCT02537613

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

Recruiting

Sponsor: Dana-Farber Cancer Institute

Collaborators: Genentech, Inc.

Information provided by (Responsible party): Principal Investigator Dana-Farber Cancer Institute Matthew S. Davids, MD Principal Investigator

ClinicalTrials.gov Identifier: NCT02537613

Protocol Info

Short Description: Phase IB Ibrutinib+ Obinutuzumab in Chronic Lymphocytic Leukemia
Long Description: A Phase IB Study of Ibrutinib in Combination with Obinutuzumab in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia
MGH Status: Open
Sponsor: DF/HCC
Disease Program: Lymphoma

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

This research study is evaluating a combination of two drugs, ibrutinib and obinutuzumab, as a possible treatment for Chronic Lymphocytic Leukemia (CLL).
Condition Title Intervention Phase
Chronic Lymphocytic Leukemia Obinutuzumab Ibrutinib Phase 1
Study Type Interventional
Official Title A Phase Ib Study of Ibrutinib in Combination With Obinutuzumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Primary Outcome Measures

Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 [Time Frame: Baseline to 6 Months] [Designated as safety issue: ]


Secondary Outcome Measures

Overall Response Rate [Time Frame: 6 Months] [Designated as safety issue: ]

Partial Response Rate [Time Frame: 6 Months] [Designated as safety issue: ]

Complete Response Rate [Time Frame: 6 Months] [Designated as safety issue: ]

Minimal residual disease (MRD) status in the bone marrow and blood [Time Frame: 6 Months] [Designated as safety issue: ]

Duration of Response [Time Frame: 2 Years] [Designated as safety issue: ]

Progression Free Survival [Time Frame: 2 Years] [Designated as safety issue: ]

Overall Response Rate [Time Frame: 2 Years] [Designated as safety issue: ]

Estimated Enrollment: 50
Study Start Date: December 2015
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: December 2019
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:Ibrutinib
Ibrutinib given once daily by mouth

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

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.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT02537613

Locations

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

Sponsors and Collaborators

Dana-Farber Cancer Institute

Genentech, Inc.

More Information

No publications provided

Responsible Party: Principal Investigator Dana-Farber Cancer Institute Matthew S. Davids, MD Principal Investigator
ClinicalTrials.gov Identifier: NCT02537613
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Dana-Farber Cancer Institute:

Chronic Lymphocytic Leukemia

Additional relevant MeSH terms:

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Obinutuzumab

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on July 18, 2019