This research study is studying a drug as a possible treatment for IDH1-mutant myeloid neoplasms. -The drug involved in this study is ivosidenib (AG-120)
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied. The FDA (the U.S. Food and Drug Administration) has not approved ivosidenib as a treatment for any disease. Ivosidenib is an inhibitor of the protein IDH1. Ivosidenib is currently being studied as a treatment for myeloid cancers like acute myeloid leukemia or myelodysplastic syndromes with an IDH1 mutation. This study is examining whether or not ivosidenib is beneficial and well-tolerated as an agent to prevent the relapse of IDH1-mutated acute myeloid leukemia or other myeloid neoplasms after hematopoietic stem cell transplantation. IDH1 is an enzyme that, when mutated, can overproduce metabolites (substances that help with metabolism) and compounds that contribute to the growth of tumors and cancerous cells. Ivosidenib may help block the over production of these substances and possibly reduce the chances of relapse.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Ivosidenib is an inhibitor of the protein IDH1
Johns Hopkins Cancer Center
Baltimore, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Maximum Tolerated Dose
Participants will be enrolled in standard 3 + 3 dose escalation cohorts in order to determine the maximum tolerated dose (MTD). The first 3 participants will be started on 500mg of Ivosidenib, administered daily for 28 consecutive days (1 cycle). If the 500mg/day dose level is tolerated, an additional 10 participants will be treated at this dose level. If the 500mg/day dose is not tolerated, the dose will be decreased to 250mg/day. If 250mg daily is tolerated, then an additional 10 participants will be treated at 250mg daily. The only doses studied will be 500mg daily and 250mg daily (the latter, if necessary). If 250mg daily dosing is not tolerated, then the study will end without expansion. Dose limiting toxicities are assessed and graded using Common Terminology Criteria for Adverse Events (CTCAE 4).
Time frame: 28 Days
Ivosidenib-related Adverse Events, categorized by grade
Adverse events will be assessed and graded using Common Terminology Criteria for Adverse Events (CTCAE 4).
Time frame: From the start of treatment until 30 days after the end of treatment, up to 13 months total
Cumulative incidence of acute GVHD
Cumulative incidence of acute graft versus host disease (GVHD), measured from start of treatment with Ivosidenib.
Time frame: From the start of treatment with Ivosidenib until the onset of Acute GVHD, up to 100 days
Cumulative incidence of chronic GVHD
The cumulative incidence of chronic GVHD, measured from start of treatment with Ivosidenib. Chronic GVHD will be assessed using the National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease.
Time frame: From the start of treatment with Ivosidenib until the onset of chronic GVHD, up to 24 months
Plasma and marrow 2-hydroxyglutarate levels
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Time frame: Screening, cycle 1 days 8 and 15 (cycles are 28 days), before the start of cycles 2 and 3, and at the time of relapse; up 24 months total time
IDH clonal evolution and mutational burden
Isocitrate dehydrogenase (IDH) clonal evolution and mutational burden in patients with IDH1-mutant myeloid neoplasms who receive Ivosidenib after hematopoietic stem cell transplantation. Next-generation sequencing will be used to assess mutational burden (i.e. the fraction of AML cells harboring IDH mutations, corrected for copy number) at various time points. SNaPshot genotyping analysis platform will be used to perform these analyses.
Time frame: Screening, cycle 1 days 8 and 15 (cycles are 28 days), before the start of cycles 2 and 3, and at the time of relapse; up 24 months total time