Bcl-2 Inhibitor GDC-0199 in Combination With Obinutuzumab and Ibrutinib in Treating Patients With Relapsed, Refractory, or Previously Untreated Chronic Lymphocytic Leukemia
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|ClinicalTrials.gov Identifier: NCT02427451|
Recruitment Status : Recruiting
First Posted : April 28, 2015
Last Update Posted : January 21, 2019
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia Refractory Chronic Lymphocytic Leukemia||Drug: Bcl-2 Inhibitor GDC-0199 Biological: Obinutuzumab Drug: Ibrutinib Other: Pharmacological Study Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment||Phase 1 Phase 2|
I. To identify the dose of venetoclax (Bcl-2 inhibitor GDC-0199) that can be safely administered in combination with obinutuzumab and ibrutinib for the treatment of relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL).
II. To evaluate the feasibility, safety, and tolerability of venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated CLL.
III. To determine the minimal residual disease (MRD)-negative complete response (CR) rate after 12 cycles of treatment with venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated CLL.
I. To determine the overall response rate (ORR) and complete response rate (CR) of venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated patients with CLL.
II. To estimate progression free survival (PFS) after treatment with venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated patients with CLL.
III. To conduct pharmacokinetic and pharmacodynamic studies of venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated patients with CLL.
IV. To examine pre-treatment and serial biomarkers associated with response and mechanisms of resistance to venetoclax, obinutuzumab and ibrutinib when given in combination for relapsed/refractory or previously untreated patients with CLL.
OUTLINE: This is a phase Ib, dose-escalation study of Bcl-2 inhibitor GDC-0199 followed by a phase II study.
Patients receive obinutuzumab intravenously (IV) on day 1 (days 1, 2, 8, and 15 for course 1 only) every 28 days for up to 8 courses. Beginning in course 2, patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Beginning in course 3, patients receive Bcl-2 inhibitor GDC-0199 PO QD on days 1-28. Treatment repeats every 28 days for up to 14 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4 and 8 weeks, every 3 months for 2 years, and then every 6 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||87 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Obinutuzumab, Ibrutinib, and Venetoclax for Relapsed and Previously Untreated Chronic Lymphocytic Leukemia (CLL)|
|Actual Study Start Date :||July 2015|
|Estimated Primary Completion Date :||August 29, 2019|
|Estimated Study Completion Date :||August 29, 2020|
Experimental: Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199)
Patients receive obinutuzumab IV on day 1 (days 1, 2, 8, and 15 for course 1 only) every 28 days for up to 8 courses. Beginning in course 2, patients receive ibrutinib PO QD on days 1-28. Beginning in course 3, patients receive Bcl-2 inhibitor GDC-0199 PO QD on days 1-28. Treatment repeats every 28 days for up to 14 courses in the absence of disease progression or unacceptable toxicity.
Drug: Bcl-2 Inhibitor GDC-0199
Other: Pharmacological Study
Other Name: pharmacological studies
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
- Maximum tolerated dose of Bcl-2 inhibitor GDC-0199 in combination with obinutuzumab and ibrutinib (Phase Ib) [ Time Frame: 28 days (course 3) ]
- MRD-complete response (CR) defined by the IWCLL 2008 criteria (Phase II) [ Time Frame: Up to 8 weeks post-treatment ]Assessments of MRD will be used in patients classified as CR to further evaluate their status as disease-free and if this further impacts their ability to remain progression-free and alive. MRD will be determined by high sensitivity 4 color flow cytometric analysis of the bone marrow using validated panels.
- Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 4 years ]For all patients who receive at least one day of treatment, toxicities will be tabulated by type and grade and displayed in summary form.
- Number of courses started/completed [ Time Frame: Up to 14 months ]May be summarized.
- Number of patients who reach the target dose of Bcl-2 inhibitor GDC-0199 [ Time Frame: Up to 14 months ]May be summarized.
- Number of patients requiring dose reductions [ Time Frame: Up to 14 months ]May be summarized.
- Reason for going off treatment [ Time Frame: Up to 14 months ]May be summarized.
- Overall response rate [ Time Frame: Up to 4 years ]Overall response rate with a 95% confidence interval will be reported for all evaluable patients in the phase II setting, within and potentially across cohorts, assuming a binomial distribution.
- Progression-free survival [ Time Frame: Time from first treatment date until the date of progression or death, whichever occurs first, assessed up to 4 years ]Will be summarized by the Kaplan-Meier method for each of the phase II cohorts.
- Baseline prognostic factors [ Time Frame: Baseline ]Relationships between baseline prognostic factors and response may be screened and analyzed quantitatively using logistic regression and adjusting for disease cohort, particularly if a sufficient number of patients respond to this combination therapy.
- Health related quality of life [ Time Frame: Up to 2 years ]Validated instruments will be administered serially to assess longitudinal changes in measures of health related quality of life (SF-12, BIPQ)
- Serial assessment of immune effector cell number and function. [ Time Frame: Up to day 1 of course 2 ]Peripheral blood immunophenotyping will be used to enumerate immune effector cells (counts and percentages of B-, T-, and NK-cell subsets).
- Emotional distress assessment [ Time Frame: Up to 2 years ]Validated instruments will be administered serially to assess changes in emotional distress.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02427451
|Contact: The Ohio State University Comprehensive Cancer Center||1-800-293-5066||OSUCCCClinicaltrials@osumc.edu|
|Contact: Christian Fedoremail@example.com|
|United States, Ohio|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Kerry Rogers, MD 614-688-7568 Kerry.Rogers@osumc.edu|
|Contact: Christin Fedor 614-688-7568 firstname.lastname@example.org|
|Principal Investigator: Kerry Rogers, MD|
|Principal Investigator:||Kerry Rogers, MD||Ohio State University Comprehensive Cancer Center|