Back to resultsObinutuzumab With High-dose Ibrutinib for the Treatment of Patients With Chronic Lymphocytic Leukemia With Progressive Disease on Single Agent Ibrutinib.
Primary Purpose
Chronic Lymphocytic Leukemia
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
ibrutinib
obinutuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring CLL, cancer, obinutuzumab, ibrutinib, SLL
Eligibility Criteria
Inclusion Criteria:
- Clinical and phenotypic verification of B cell CLL or SLL and measurable disease.
- Prior therapy: Patients must have been receiving single agent ibrutinib therapy at the time of disease progression. Patient may have received other therapy in combination with ibrutinib earlier in the their treatment course. Prior obinutuzumab therapy is also permitted.
- Progressive disease on current single agent ibrutinib therapy (but not within the first 2 months of initiating ibrutinib therapy). Progression is based on 2008 iwCLL definition.
- ECOG performance status of 0-2.
- Adequate hematologic function.
- Adequate renal function.
- Adequate hepatic function.
Exclusion Criteria:
- Known CNS lymphoma or leukemia
- History of Richter's or prolymphocytic transformation.
- Primary ibrutinib resistance, defined by progressive disease within the first 2 months of first initiating ibrutinib therapy.
- Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP)
CLL therapy, with the exception of ibrutinib within the following timeframes:
- Chemotherapy, external beam radiation therapy, anticancer antibodies within 30 days prior to the first dose of drug on this study.
- Corticosteroid use 20mg prednisone within 1 week prior to first dose on this study.
- Radio- or toxin-conjugated antibody therapy within 10 weeks prior to first dose on this study.
- Allogeneic stem cell transplant within 6 months prior to first dose on this study
- History of major surgery within 4 weeks prior to first dose on this study.
- History of prior malignancy, with the exception of adequately treated non-melanoma skin cancer, malignancies treated with curative intent and with no evidence of active disease for more than 3 years, or adequately treated cervical carcinoma in situ without current evidence of disease.
- Currently active clinically significant cardiovascular disease or history of myocardial infarction within 6 months of first dose.
- Serologic status and/or PCR testing reflecting active hepatitis B or C infection.
- Known history of infection with human immunodeficiency virus (HIV).
- Unable to swallow capsules or disease significantly affecting gastrointestinal function.
- History of stroke or intracranial hemorrhage within 6 months of first dose.
- Requires anticoagulation with warfarin or other Vitamin K antagonists.
- Requires treatment with a strong CYP 3A inhibitor.
- Pregnant or breast-feeding women
- Women of child-bearing age must obtain a pregnancy test and pregnant or breast feeding females
- Patients who are currently receiving another investigational therapy
- Current infection requiring parenteral antibiotics.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ibrutinib +obinutuzumab
Arm Description
Outcomes
Primary Outcome Measures
Maximum tolerated dose
Secondary Outcome Measures
Treatment-emergent adverse events
overall response rate
progression free survival
stable disease rate
Full Information
NCT ID
NCT02611908
First Posted
November 19, 2015
Last Updated
January 23, 2019
Sponsor
Michael Choi
Collaborators
Pharmacyclics LLC.
1. Study Identification
Unique Protocol Identification Number
NCT02611908
Brief Title
Obinutuzumab With High-dose Ibrutinib for the Treatment of Patients With Chronic Lymphocytic Leukemia With Progressive Disease on Single Agent Ibrutinib.
Official Title
A Phase 1 Clinical Trial to Evaluate Obinutuzumab With High-dose Ibrutinib for the Treatment of Patients With Chronic Lymphocytic Leukemia With Progressive Disease on Single Agent Ibrutinib.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Withdrawn
Why Stopped
No participants enrolled
Study Start Date
June 2016 (undefined)
Primary Completion Date
November 2019 (Anticipated)
Study Completion Date
November 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Michael Choi
Collaborators
Pharmacyclics LLC.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to investigate whether the combination of obinutuzumab and ibrutinib (administered up to 840 mg per day) might be useful for the treatment of CLL or SLL that is not responding or no longer responding to treatment with ibrutinib alone. The study will evaluate whether this regimen can reduce the amount of cancerous cells in the body. Subjects will be treated with ibrutinib at a dose of up to 840 mg a day by mouth, as well as obinutuzumab infusions. Although both of these agents are approved by the FDA for the treatment of CLL or SLL, the combination and the dosing schedule of ibrutinib are considered experimental.
Detailed Description
This is phase 1 study for patients with CLL or small lymphocytic lymphoma (SLL) experiencing disease progression on single ibrutinib. This study will evaluate the optimal ibrutinib dose (including doses higher than 420 mg) when combined with obinutuzumab.
During the screening period, patients will continue on ibrutinib at their previous tolerated dose, unless required to stop (e.g.: by a preceding clinical trial).
On cycle 1, day 1, the dose of ibrutinib will be assigned based on the dose cohort. Patients in cohort 1 will receive ibrutinib 420 mg PO daily. Patients in cohort 2 will receive ibrutinib 560 mg PO daily. Cohort 3 will be 700 mg PO daily. Cohort 4 will be 840 mg PO daily.
On cycle 1, day 1, patients will also initiate treatment with obinutuzumab (100 mg on day 1, 900mg on day 2, 1000mg day 8, 15, 28 then q 28 days for a total of 8 doses).
The primary safety endpoint is determination of DLTs during the first 28 days. The primary efficacy endpoint of overall response rate will be assessed 2 months after the final dose of obinutuzumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
Keywords
CLL, cancer, obinutuzumab, ibrutinib, SLL
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ibrutinib +obinutuzumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ibrutinib
Other Intervention Name(s)
Imbruvica
Intervention Description
Cohort 1 420 mg PO daily Cohort 2 560 mg PO daily Cohort 3 700 mg PO daily Cohort 4 840 mg PO daily
Intervention Type
Drug
Intervention Name(s)
obinutuzumab
Other Intervention Name(s)
Gazyva
Intervention Description
obinutuzumab 100 mg IV on day 1, 900mg IV on day 2, 1000mg IV day 8, 15, 28 then q 28 days for a total of 8 doses.
Primary Outcome Measure Information:
Title
Maximum tolerated dose
Time Frame
2 months
Secondary Outcome Measure Information:
Title
Treatment-emergent adverse events
Time Frame
2 years
Title
overall response rate
Time Frame
2 months
Title
progression free survival
Time Frame
2 months
Title
stable disease rate
Time Frame
2 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical and phenotypic verification of B cell CLL or SLL and measurable disease.
Prior therapy: Patients must have been receiving single agent ibrutinib therapy at the time of disease progression. Patient may have received other therapy in combination with ibrutinib earlier in the their treatment course. Prior obinutuzumab therapy is also permitted.
Progressive disease on current single agent ibrutinib therapy (but not within the first 2 months of initiating ibrutinib therapy). Progression is based on 2008 iwCLL definition.
ECOG performance status of 0-2.
Adequate hematologic function.
Adequate renal function.
Adequate hepatic function.
Exclusion Criteria:
Known CNS lymphoma or leukemia
History of Richter's or prolymphocytic transformation.
Primary ibrutinib resistance, defined by progressive disease within the first 2 months of first initiating ibrutinib therapy.
Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP)
CLL therapy, with the exception of ibrutinib within the following timeframes:
Chemotherapy, external beam radiation therapy, anticancer antibodies within 30 days prior to the first dose of drug on this study.
Corticosteroid use 20mg prednisone within 1 week prior to first dose on this study.
Radio- or toxin-conjugated antibody therapy within 10 weeks prior to first dose on this study.
Allogeneic stem cell transplant within 6 months prior to first dose on this study
History of major surgery within 4 weeks prior to first dose on this study.
History of prior malignancy, with the exception of adequately treated non-melanoma skin cancer, malignancies treated with curative intent and with no evidence of active disease for more than 3 years, or adequately treated cervical carcinoma in situ without current evidence of disease.
Currently active clinically significant cardiovascular disease or history of myocardial infarction within 6 months of first dose.
Serologic status and/or PCR testing reflecting active hepatitis B or C infection.
Known history of infection with human immunodeficiency virus (HIV).
Unable to swallow capsules or disease significantly affecting gastrointestinal function.
History of stroke or intracranial hemorrhage within 6 months of first dose.
Requires anticoagulation with warfarin or other Vitamin K antagonists.
Requires treatment with a strong CYP 3A inhibitor.
Pregnant or breast-feeding women
Women of child-bearing age must obtain a pregnancy test and pregnant or breast feeding females
Patients who are currently receiving another investigational therapy
Current infection requiring parenteral antibiotics.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Choi, MD
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Obinutuzumab With High-dose Ibrutinib for the Treatment of Patients With Chronic Lymphocytic Leukemia With Progressive Disease on Single Agent Ibrutinib.
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