Ipilimumab and Decitabine in Treating Patients With Relapsed or Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia
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ClinicalTrials.gov Identifier: NCT02890329 |
Recruitment Status :
Active, not recruiting
First Posted : September 7, 2016
Last Update Posted : March 21, 2024
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Tracking Information | |||||
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First Submitted Date ICMJE | September 1, 2016 | ||||
First Posted Date ICMJE | September 7, 2016 | ||||
Last Update Posted Date | March 21, 2024 | ||||
Actual Study Start Date ICMJE | September 5, 2017 | ||||
Estimated Primary Completion Date | July 1, 2024 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Maximum tolerated dose (recommended phase 2 dose) of ipilimumab in combination with decitabine [ Time Frame: Up to 56 days ] Defined as the highest dose at which 1 or fewer of 6 patients experience a dose limiting toxicity graded by Common Terminology Criteria for Adverse Events version 5.0 criteria.
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Original Primary Outcome Measures ICMJE |
MTD (RP2D) of ipilimumab in combination with decitabine defined as the highest dose at which 1 or fewer of 6 patients experience a dose limiting toxicity (DLT) graded by Common Terminology Criteria for Adverse Events version 4.03 (CTCAE V.4.03) criteria [ Time Frame: Up to 56 days ] | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
Ability of absolute lymphocyte count to predict response [ Time Frame: Up to cycle 3 day 1 ] Absolute lymphocyte count levels will be divided into: low (< 1000 cells/ul) and normal/high (greater than or equal to 1000 cells/ul). The response and overall survival of patients with low absolute lymphocyte count versus normal/high absolute lymphocyte count will be compared using Kaplan-Meier estimates and the differences will be assessed using log-rank test.
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Original Other Pre-specified Outcome Measures |
Ability of ALC to predict response [ Time Frame: Up to course 3 day 1 ] ALC levels will be divided into: low (<1000 cells/ul) and normal/high (greater than or equal to 1000 cells/ul). The response and overall survival of patients with low ALC versus normal/high ALC will be compared using Kaplan-Meier estimates and the differences will be assessed using log-rank test.
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Descriptive Information | |||||
Brief Title ICMJE | Ipilimumab and Decitabine in Treating Patients With Relapsed or Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia | ||||
Official Title ICMJE | A Phase 1 Study of Ipilimumab in Combination With Decitabine in Relapsed or Refractory Myelodysplastic Syndrome/Acute Myeloid Leukemia | ||||
Brief Summary | This phase I trial studies the side effects and best dose of ipilimumab when given together with decitabine in treating patients with myelodysplastic syndrome or acute myeloid leukemia that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ipilimumab and decitabine may work better in treating patients with relapsed or refractory myelodysplastic syndrome or acute myeloid leukemia. | ||||
Detailed Description | PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of combination decitabine and ipilimumab for relapsed or refractory myelodysplastic syndrome (MDS) or relapsed or refractory acute myeloid leukemia (AML) in patients who are post allogeneic hematopoietic stem cell transplant (allo-HCT). II. To determine the MTD or RP2D of combination decitabine and ipilimumab for relapsed or refractory MDS or relapsed or refractory AML in patients who are transplant naive. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To determine the overall response rate (ORR) including complete remission (CR) and complete remission with incomplete count recovery (CRi) for AML following 2003 International Working Group (IWG) response criteria. III. To determine the ORR including CR, partial remission, marrow CR, hematologic improvement for MDS using 2006 IWG criteria. IV. To determine the overall survival and progression free survival at 1 year. V. To determine the duration of remission. VI. To capture the incidence and severity of acute graft-versus-host disease (GVHD) in the post allo-HCT cohort. VII. To capture the incidence and severity of chronic graft-versus-host disease (GVHD) in the post allo-HCT cohort. EXPLORATORY OBJECTIVES: I. To measure the absolute lymphocyte count (ALC) prior to treatment and during treatment. II. To evaluate the genome for evidence of clonal evolution among longitudinal samples (prior to treatment, during treatment, and at relapse if relevant) from individual patients. III. To evaluate the histopathologic findings of immune response using immunohistochemistry. IV. To determine the immune response in the AML tumor microenvironment by using flow cytometry and single cell mass cytometry to evaluate T cell subsets. OUTLINE: This is a dose-escalation study of ipilimumab. ARM A (PATIENTS POST ALLO-HCT): PRIMING PHASE: Patients receive decitabine intravenously (IV) over 60 minutes on days 1-5 out of 28 days. INDUCTION PHASE: Patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 4 or 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. ARM B (TRANSPLANT NAIVE PATIENTS): PRIMING PHASE: Patients receive decitabine IV over 60 minutes on days 1-5 out of 28 days. INDUCTION PHASE: Patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 4 or 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 52 weeks (1 year). |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 | ||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Active, not recruiting | ||||
Estimated Enrollment ICMJE |
48 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | July 1, 2024 | ||||
Estimated Primary Completion Date | July 1, 2024 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT02890329 | ||||
Other Study ID Numbers ICMJE | NCI-2016-01326 NCI-2016-01326 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 17-718 10026 ( Other Identifier: Dana-Farber - Harvard Cancer Center LAO ) 10026 ( Other Identifier: CTEP ) UM1CA186709 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Current Responsible Party | National Cancer Institute (NCI) | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | National Cancer Institute (NCI) | ||||
Verification Date | March 2024 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |