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

Primary Purpose

Chronic Lymphocytic Leukemia

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

GA101

ibrutinib

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring CLL, Chronic Lymphocytic Leukemia, Ibrutinib, Obinutuzumab, Cancer

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of CLL
Indication for treatment as defined by the International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) Guidelines
No previous treatment for CLL
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
Adequate hematologic, hepatic, and renal function
Anticipated survival of at least 6 months
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:

Pregnant or nursing women
Treatment with chemotherapy, monoclonal antibodies, or biological agents (e.g. lenalidomide) other than the investigational agents during the time of participation in this trial
Grade 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
Severe or debilitating pulmonary disease
Participation in any investigational drug study within 28 days prior to initiation of treatment within this protocol.
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.
Active symptomatic fungal, bacterial and/or viral infection including evidence of infection with HIV, human T-cell leukemia virus 1 (HTLV-1) seropositive status.
Evidence of active acute or chronic Hepatitis B (HBV)
Evidence of active Hepatitis C (HCV): subjects with positive hepatitis C serology and positive HCV RNA test
History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
Known hypersensitivity to any of the study drugs
Major surgery (within 4 weeks prior to the start of Cycle 1), except for procedures that are performed for diagnostic purposes
Vaccination with a live vaccine within 28 days of the initiation of treatment.
Concomitant use of warfarin or other Vitamin K antagonists
Requirement to receive treatment with a strong cytochrome P450 (CYP) 3A inhibitor
Chronic liver disease with hepatic impairment (Child-Pugh class B or C)

Sites / Locations

UCSD Moores Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GA101+ibrutinib

Arm Description

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.

Outcomes

Primary Outcome Measures

Phase IB Evaluate the safety, tolerability and dose limiting toxicity (DLT) of Ibrutinib in combination with Obinutuzumab in previously untreated CLL subjects.

Phase II Determine the overall response rate of Ibrutinib in combination with Obinutuzumab in previously untreated subjects with CLL.

Secondary Outcome Measures

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.

Negative minimal residual disease (MRDneg)

Full Information

NCT ID

NCT02315768

First Posted

October 30, 2014

Last Updated

July 1, 2022

Sponsor

University of California, San Diego

Collaborators

Pharmacyclics LLC.

1. Study Identification

Unique Protocol Identification Number

NCT02315768

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

November 2015 (undefined)

Primary Completion Date

November 2023 (Anticipated)

Study Completion Date

November 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, San Diego

Collaborators

Pharmacyclics LLC.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Lymphocytic Leukemia

Keywords

CLL, Chronic Lymphocytic Leukemia, Ibrutinib, Obinutuzumab, Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

GA101+ibrutinib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

GA101

Other Intervention Name(s)

Obinutuzumab

Intervention Type

Drug

Intervention Name(s)

ibrutinib

Primary Outcome Measure Information:

Title

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

Title

Phase II Determine the overall response rate of Ibrutinib in combination with Obinutuzumab in previously untreated subjects with CLL.

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Time Frame

2 years

Title

Negative minimal residual disease (MRDneg)

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of CLL Indication for treatment as defined by the International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) Guidelines No previous treatment for CLL 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 Adequate hematologic, hepatic, and renal function Anticipated survival of at least 6 months 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: Pregnant or nursing women Treatment with chemotherapy, monoclonal antibodies, or biological agents (e.g. lenalidomide) other than the investigational agents during the time of participation in this trial Grade 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification Severe or debilitating pulmonary disease Participation in any investigational drug study within 28 days prior to initiation of treatment within this protocol. 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. Active symptomatic fungal, bacterial and/or viral infection including evidence of infection with HIV, human T-cell leukemia virus 1 (HTLV-1) seropositive status. Evidence of active acute or chronic Hepatitis B (HBV) Evidence of active Hepatitis C (HCV): subjects with positive hepatitis C serology and positive HCV RNA test History of severe allergic or anaphylactic reactions to monoclonal antibody therapy Known hypersensitivity to any of the study drugs Major surgery (within 4 weeks prior to the start of Cycle 1), except for procedures that are performed for diagnostic purposes Vaccination with a live vaccine within 28 days of the initiation of treatment. Concomitant use of warfarin or other Vitamin K antagonists Requirement to receive treatment with a strong cytochrome P450 (CYP) 3A inhibitor Chronic liver disease with hepatic impairment (Child-Pugh class B or C)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas J. Kipps, MD, PhD

Organizational Affiliation

University of California, San Diego

Official's Role

Principal Investigator

Facility Information:

Facility Name

UCSD Moores Cancer Center

City

La Jolla

State/Province

California

ZIP/Postal Code

92093

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

35103064

Citation

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.

Results Reference

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

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