FRIDA: Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+)
Study Details
Study Description
Brief Summary
This is an escalation/expansion, open label, multicenter study to investigate the safety and the RP2D of the combination of iadademstat with gilteritinib in FLT3-mutated R/R AML.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Active arm iadademstat and gilteritinib |
Drug: Iadademstat
iadademstat oral solution
Other Names:
Drug: Gilteritinib Oral Tablet
120 mg Gilteritinib
|
Outcome Measures
Primary Outcome Measures
- Adverse Events (AE) [Up to 18 months]
Number of participants with Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
- Laboratory value abnormalities and/or adverse events (AE) [Up to 18 months]
Number of participants with laboratory value abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
- Vital sign abnormalities and/or adverse events (AEs) [Up to 18 months]
Number of participants with vital signs abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
- Routine 12-lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs) [Up to 18 months]
Number of participants with Routine 12-lead electrocardiogram (ECG )abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
- Recommend Phase 2 dose (RP2D) [Up to 18 months]
Determine the recommended Phase 2 dose (RP2D) of iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R
- iadademstat tmax [Up to 26 days]
Measurement of the time it takes for iadademstat to reach the maximum concentration (Cmax) in blood.
- Iadademstat Cmax [Up to 26 days]
Measurement of the highest concentration of iadademstat in the blood after a dose is given.
- iadademstat Cmin [Up to 26 days]
Measurement of the lowest concentration of iadademstat in the blood, after a dose is given.
- iadademstat AUC [Up to 26 days]
Measurement of how much iadadmestat reaches a person's bloodstream in a given period of time after a dose is given.
- iadademstat Target Engagement (TE) [Up to 26 days]
- OR rate [Up to 18 months]
Proportion of patients achieving complete remission (CR), CR with incomplete hematologic recovery (CRi), and partial remission (PR).
Secondary Outcome Measures
- Overall Survival (OS) [Up to 24 months]
Time from start of treatment to the time of death from any cause.
- Event-Free-Survival (EFS) [Up to 18 months]
Time from start of treatment to the date of failure to achieve CR or CRi, relapse from CR/CRi, or death from any cause, whichever occurs first.
- Overall response rate [Up to 6 months]
Percentage of patients with complete remission (CR), CR with incomplete blood count recovery (CRi), or PR.
- Time to Response (TTR) [Up to 6 months]
Time from the date of initial dosing at RP2D/expansion dose to first documentation of either a type of CR or Partial Response (PR).
- Duration of Remission (DoR) [Up to 18 months]
Time from the date of first documentation of any type of remission to the date of first documentation of progression of remission for remitters
- Transfusion independence rate [Up to 18 months]
A patient is defined as red blood cell (RBC) and/or platelet-transfusion independent if he/she receives no RBC and/or platelet transfusions for a period of at least 8 weeks. Rate of transfusion independence is the percentage of patients who become RBC and/or platelet transfusion independent (from the number of patients transfusion dependent at baseline).
- Transplantation Rate Time Frame [Up to 18 months]
Percentage of patients undergoing Hematopoietic Stem Cell Transplantation (HSCT) during the study period.
Eligibility Criteria
Criteria
Main Inclusion Criteria:
-
Diagnosis of primary AML or AML with myelodysplasia-related changes (AML-MRC)
-
Patient is in first or second relapse or has refractory disease. Patients must have had histologic verification of AML at the original diagnosis.
-
Patient must be positive for the following FLT3 mutations in bone marrow or PB: FLT3 internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD) D835 or I836 or FLT3-ITD and specified FLT3-TKD.
-
ECOG performance status 0-2
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Life expectancy of at least 3 months in the opinion of the investigator.
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Normal hepatic and renal function.
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Patient is able to swallow oral medications.
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Female patients are postmenopausal, documented as surgically sterile, use two methods of contraception or practice true abstinence and have a negative urine pregnancy test at screening.
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Male patients even if surgically sterilized agree to practice true abstinence or use highly effective barrier contraception.
Main Exclusion Criteria:
-
Diagnosis of acute promyelocytic leukemia.
-
Known BCR-ABL-positive leukemia.
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AML secondary to prior chemotherapy for other neoplasms (except for MDS).
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AML that has relapsed after or is refractory to more than 2 lines of therapy.
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Clinically active central nervous system leukemia or prior history of NCI CTCAE Grade ≥ 3 drug-related CNS toxicity.
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Major surgery or radiation therapy within 4 weeks prior to the first study dose.
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Prior treatment with iadademstat or FLT3 inhibitors (except sorafenib or midostaurin used in first line as part of induction).
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Patients not eligible to receive gilteritinib per label.
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Prior treatment with 3 or more lines of AML therapy.
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Treatment with any investigational products within 3 weeks prior to first dose of study treatment.
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Uncontrolled hypertension or poorly controlled diabetes.
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Evidence of active uncontrolled viral, bacterial, or systemic fungal infection.
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Pregnant or lactating women.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Massachusetts General Hospital (MGH) | Boston | Massachusetts | United States | 02114 |
Sponsors and Collaborators
- Oryzon Genomics S.A.
Investigators
- Study Chair: Douglas Faller, PhD, Oryzon Genomics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CL04-ORY-1001