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

NCT ID: NCT02315768

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-26
• Study Completion Date: 2022-04-18

Brief Summary

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.

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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

GA101

Intervention Type: DRUG

Ibrutinib

Intervention Type: DRUG

Interventions

GA101

Intervention Type: DRUG

Ibrutinib

Intervention Type: DRUG

Other Intervention Names

Obinutuzumab; Imbruvica

Eligibility Criteria

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)

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmacyclics LLC.

INDUSTRY

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Thomas Kipps

Deputy Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas J. Kipps, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

UCSD Moores Cancer Center

La Jolla, California, United States

Countries

United States

References

Castro JE, Lengerke-Diaz PA, Velez Lujan J, Choi MY, Moreno-Cortes EF, Forero JV, Garcia-Robledo JE, Jacobs C, McCarthy C, Heinen A, Amaya-Chanaga CI, Kipps TJ. Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Trial NCT0231576. Adv Hematol. 2022 Jan 22;2022:4450824. doi: 10.1155/2022/4450824. eCollection 2022.

Reference Type: DERIVED

PMID: 35103064 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

141106

Identifier Type: -

Identifier Source: org_study_id