Chronic Lymphocytic Leukemia
Conditions
Keywords
CLL, Chronic Lymphocytic Leukemia, Ibrutinib, Obinutuzumab, Cancer
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.
Interventions
DRUGGA101
DRUGIbrutinib
Sponsors
Pharmacyclics LLC.
University of California, San Diego
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety, Tolerability and Dose Limiting Toxicity (DLT) of Ibrutinib in Combination With Obinutuzumab | 4 weeks | Remission rate after discontinuation of Ibrutinib in patients with previously untreated CLL treated with Ibrutinib in combination with Obinutuzumab |
| Overall Response Rate of Ibrutinib in Combination With Obinutuzumab | 2 years | Determine the overall response rate of Ibrutinib in combination with Obinutuzumab in previously untreated subjects with CLL. Overall response rate was based on the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2008 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
GA101
ibrutinib | 32 |
| Total | 32 |
Baseline characteristics
| Characteristic | GA101+Ibrutinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 32 / 32 |
| serious Total, serious adverse events | 3 / 32 |
Outcome results
Primary
Overall Response Rate of Ibrutinib in Combination With Obinutuzumab
Determine the overall response rate of Ibrutinib in combination with Obinutuzumab in previously untreated subjects with CLL. Overall response rate was based on the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2008 criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GA101+Ibrutinib | Overall Response Rate of Ibrutinib in Combination With Obinutuzumab | 32 Participants |
Primary
Safety, Tolerability and Dose Limiting Toxicity (DLT) of Ibrutinib in Combination With Obinutuzumab
Remission rate after discontinuation of Ibrutinib in patients with previously untreated CLL treated with Ibrutinib in combination with Obinutuzumab
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GA101+Ibrutinib | Safety, Tolerability and Dose Limiting Toxicity (DLT) of Ibrutinib in Combination With Obinutuzumab | 32 Participants |