Ibrutinib in Combination With GA101 (Obinutuzumab) in Previously Untreated Chronic Lymphocytic Leukemia (CLL) Patients.

November 27, 2023 updated by: Thomas Kipps, University of California, San Diego

A Phase Ib/II Study of Ibrutinib in Combination With GA101 - Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia (CLL) Patients Over 65 Years of Age or With Comorbidities That Preclude the Use of Chemotherapy Based Treatment. GA101+Ibrutinib

The purpose of the study is to determine whether ibrutinib in combination with GA101 - Obinutuzumab might be useful for the treatment of CLL. This study will evaluate if ibrutinib in combination with GA101 - Obinutuzumab can reduce the amount of cancerous cells in body.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an open label phase IB/II clinical trial designed to determine the safety and clinical activity of Ibrutinib in combination with GA101 - Obinutuzumab. Safety, tolerability and dose-limiting toxicities (DLTs) will be evaluated during the initial cycle of treatment (Cycle 1; Day 1-28) as part of the phase Ib of this study (safety run-in).

In the phase II the response rate will be determined in all subjects that have received treatment. The study will enroll 32 subjects previously untreated who have active disease requiring treatment (as defined by IWCLL 2008 criteria for initiation of therapy). The study will include a Screening Phase, a Treatment Phase, and a Follow-up Phase. The Screening Phase assessments will be performed within 28 days prior to treatment. The Treatment Phase will extend from first dose until completion of all planned cycles of treatment (#6) or study drug discontinuation.

All subjects will receive Ibrutinib 420 mg (3 x 140-mg capsules) orally once daily for up to 6 cycles. The treatment with Ibrutinib will continue after cycle 6 for the following 3 years until disease progression, unacceptable toxicity or other reason for treatment discontinuation.

Subjects will undergo response assessment two months after completion of the study treatment. The initial follow-up evaluations will be made (after the response assessment) every 3 months during 9 months and later every 6 months until initiation of new treatment for CLL, consent withdrawal or death. During the long-term follow-up phase, subjects will be followed for survival (PFS, TFS and OS). The long-term follow-up phase will continue until disease progression, death, loss to follow up, consent withdrawal, or study end, whichever occurs first.

An evaluation of the End of Study will be performed due to initiation of new treatment for CLL or withdrawal of consent.

Study Type

Interventional

Enrollment (Estimated)

32

Phase

  • Phase 2
  • 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
    • California
      • La Jolla, California, United States, 92093
        • UCSD Moores Cancer 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

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Diagnosis of CLL
  2. Indication for treatment as defined by the International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) Guidelines
  3. No previous treatment for CLL

  4. Males and females 65 years of age and older. Subjects under 65 years of age that meet any of the following criteria:

    A. Documented refusal to be treated with chemotherapy agents B. Subjects that are not candidates for treatment with chemotherapy based on poor performance status (ECOG g>= 2), Cumulative Illness Rating Scale (CIRS score) >= 6 or creatinine clearance less than 70 mL/min

  5. Adequate hematologic, hepatic, and renal function
  6. Anticipated survival of at least 6 months
  7. Effective contraception is required while receiving Ibrutinib in combination with GA101-Obinutuzumab. For women of childbearing potential and men, effective contraception is required while receiving GA101-Obinutuzumab and for 365 days (12 months) after the last dose of the study drug

Exclusion Criteria:

  1. Pregnant or nursing women
  2. Treatment with chemotherapy, monoclonal antibodies, or biological agents (e.g. lenalidomide) other than the investigational agents during the time of participation in this trial
  3. Grade 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
  4. Severe or debilitating pulmonary disease
  5. Participation in any investigational drug study within 28 days prior to initiation of treatment within this protocol.
  6. History of second malignancy, other than non-melanoma skin cancer or in situ carcinoma of the cervix or the breast, unless the tumor was successfully treated at least 2 years before trial entry and with no evidence of relapse or active cancer.
  7. Active symptomatic fungal, bacterial and/or viral infection including evidence of infection with HIV, human T-cell leukemia virus 1 (HTLV-1) seropositive status.
  8. Evidence of active acute or chronic Hepatitis B (HBV)
  9. Evidence of active Hepatitis C (HCV): subjects with positive hepatitis C serology and positive HCV RNA test
  10. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
  11. Known hypersensitivity to any of the study drugs
  12. Major surgery (within 4 weeks prior to the start of Cycle 1), except for procedures that are performed for diagnostic purposes
  13. Vaccination with a live vaccine within 28 days of the initiation of treatment.
  14. Concomitant use of warfarin or other Vitamin K antagonists
  15. Requirement to receive treatment with a strong cytochrome P450 (CYP) 3A inhibitor
  16. Chronic liver disease with hepatic impairment (Child-Pugh class B or C)

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GA101+ibrutinib

Ibrutinib 420 mg (140 mg capsules 3 times) orally once daily for up to 6 cycles.

GA101 (Obinutuzumab) by Intravenous infusion for up to 6 cycles (28 day cycles) as follows:

  • Cycle 1, Day 1,100 mg GA101 obinutuzumab will be administered.
  • Cycle 1, Day 2, 900 mg of GA101 obinutuzumab will be administered.
  • Cycle 1, Days 8 and 15,1,000 mg of GA101 obinutuzumab will be administered.
  • Cycles 2-6, Day 1, 1,000 mg of GA101 obinutuzumab will be administered.
Drug: ibrutinib
Drug: GA101
Other Names:
  • Obinutuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase IB Evaluate the safety, tolerability and dose limiting toxicity (DLT) of Ibrutinib in combination with Obinutuzumab in previously untreated CLL subjects.
Time Frame: 4 weeks
4 weeks
Phase II Determine the overall response rate of Ibrutinib in combination with Obinutuzumab in previously untreated subjects with CLL.
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Determine progression-free survival (PFS), treatment-free survival (TFS) and overall survival (OS) in previously untreated CLL subjects that will receive treatment with Ibrutinib in combination with Obinutuzumab.
Time Frame: 2 years
2 years
Negative minimal residual disease (MRDneg)
Time Frame: 2 years
2 years

Collaborators and Investigators

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

Sponsor

University of California, San Diego

Collaborators

Pharmacyclics LLC.

Investigators

  • Principal Investigator: Thomas J. Kipps, MD, PhD, University of California, San Diego

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

August 26, 2015

Primary Completion (Estimated)

November 1, 2023

Study Completion (Estimated)

November 1, 2023

Study Registration Dates

First Submitted

October 30, 2014

First Submitted That Met QC Criteria

December 11, 2014

First Posted (Estimated)

December 12, 2014

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 27, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 141106

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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