ASTX727 and FT-2102 in Treating IDH1-Mutated Recurrent/Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT04013880|
Recruitment Status : Withdrawn (Loss of funding)
First Posted : July 10, 2019
Last Update Posted : July 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Recurrent Myelodysplastic Syndrome Refractory Acute Myeloid Leukemia Refractory Myelodysplastic Syndrome||Drug: CDA Inhibitor E7727/Decitabine Combination Agent ASTX727 Drug: IDH-1 Inhibitor FT-2102||Phase 1 Phase 2|
- To evaluate the safety of IDH-1 inhibitor FT-2102 (FT-2102) in combination with CDA inhibitor E7727/decitabine combination agent ASTX727 (ASTX727) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients with IDH1 R132 mutations. (Phase Ib)
- To evaluate the response rate (overall response rate [ORR], complete response [CR], complete remission with partial hematologic recovery (CRh), complete remission with incomplete blood count recovery [CRi], morphologic leukemia-free state [MLFS], partial response [PR]) of the combination of ASTX727 and the IDH1-inhibitor, FT-2102 in subjects with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with IDH1 R132 mutations. (Phase II)
- To confirm the phase II recommended dosing level of FT-2102 and ASTX727 in combination. (Phase Ib)
- To determine the pharmacokinetics of FT-2102 and ASTX727 in combination. (Phase Ib)
- To determine the reduction of bone marrow blasts. (Phase II)
- To determine the overall survival and event-free survival. (Phase II)
- To determine the levels of 2-HG in the blood and blood cells after treatment. (Phase II)
- To determine the relationship of 2-HG reduction to clinical response. (Phase II)
OUTLINE: This is a phase Ib, dose-escalation of IDH-1 inhibitor FT-2102 followed by a phase II study.
Patients receive CDA inhibitor E7727/decitabine combination agent ASTX727 orally (PO) once daily (QD) on days 1-5 and IDH-1 inhibitor FT-2102 PO QD or twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 12 months, and then periodically for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase IB/II Study to Evaluate the Safety, Tolerability, and Efficacy of ASTX727 and FT-2102 in IDH1-Mutated Myelodysplastic Syndrome or Acute Myeloid Leukemia|
|Actual Study Start Date :||August 27, 2019|
|Estimated Primary Completion Date :||March 31, 2021|
|Estimated Study Completion Date :||March 31, 2022|
Experimental: Treatment (ASTX727, FT-2102)
Patients receive CDA inhibitor E7727/decitabine combination agent ASTX727 PO QD on days 1-5 and IDH-1 inhibitor FT-2102 PO QD or BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: CDA Inhibitor E7727/Decitabine Combination Agent ASTX727
Given by mouth
Other Name: ASTX727
Drug: IDH-1 Inhibitor FT-2102
Given by mouth
Other Name: FT 2102, FT-2102, IDH1-R132 Inhibitor FT-2102
- Incidence of adverse events (Phase Ib) [ Time Frame: Up to 30 days ]Graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
- Response rate (Phase II) [ Time Frame: Approximately 12 months ]calculated for each cohort, together with 95% confidence intervals based on exact binomial distributions.
- To confirm the phase II recommended dosing level (1b) [ Time Frame: At 28 days ]
- Pharmacokinetics parameters (1b) [ Time Frame: Approximately 12 months ]analysis of plasma concentrations during the dose escalation phase of the study
- Reduction of bone marrow blasts (phase II) [ Time Frame: Approximately 12 months ]
- Overall survival (Phase II) [ Time Frame: Up to 2 years ]Time from randomization to death due to any cause
- Event-Free Survival (Phase II) [ Time Frame: Up to 2 years ]Time from start of treatment to event that treatment was intended to prevent or delay
- Measure change in levels of 2-HG in the blood and blood cells after treatment (Phase II) [ Time Frame: Up to 12 months ]
- Compare 2-HG change to clinical response (Phase II) [ Time Frame: Up to 12 months ]
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): NCT04013880
|Principal Investigator:||Paul Ferrell, MD||Vanderbilt Medical Center|