Induction Therapy for Patients With FLT3 Mutated Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This is a pilot study designed to identify the effect of daunorubicin-cytarabine liposome (CPX-351) in combination with a FLT3-inhibitor (midostaurin) as induction and consolidation therapy for patients with high-risk FLT3 mutated acute myeloid leukemia (AML) and subsequent CD34+-selected allogeneic stem cell transplant from HLA compatible related or unrelated donors.

Official Title
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A Pilot Study of Daunorubicin-cytarabine Liposome (CPX-351) Plus FLT3-inhibitor (Midostaurin) as Induction Therapy for Patients With FLT3 Mutated Acute Myeloid Leukemia Followed by Consolidation With a CD34+-Selected Allograft

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: CPX-351
* Drug: Midostaurin
* Drug: Busulfan
* Drug: Melphalan
* Drug: Fludarabine
* Biological: CD34+ selected allogeneic stem cell transplant from an HLA-compatible donor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a Karnofsky (adult) Performance Status of at least 70%. Patients must have adequate organ function Exclusion Criteria: Female patients who are pregnant or breast-feeding Active viral, bacterial or fungal infection Patient seropositive for Human Immunodeficiency Virus (HIV-I /II); Human T-Cell Lymphotrophic Virus (HTLV -I /II) Presence of leukemia in the Central Nervous System (CNS).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational Treatment<br>Daunorubicin-cytarabine liposome (CPX-351) Plus FLT3-inhibitor (Midostaurin) Induction Therapy followed by Busulfan/Melphalan/Fludarabine Conditioning therapy and CD34+-selected allografts. | Drug: CPX-351<br>* For this trial, patients will be treated with CPX-351 100 (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2) for 3 doses on days 1, 3 and 5 of one and on days 1 + 3 of a second cycle of induction therapy, depending on response obtained following the first induction. Thereafter, up to 2 cycles of consolidation therapy of 2 doses on days 1 and 3 of daunorubicin 29 mg/m2 and cytarabine 65 mg/m2 will be administered to the patients.<br>Drug: Midostaurin<br>* The FLT3 directed inhibitor, midostaurin, will be given at a dose of 50mg twice daily, starting on day 8 through day 21 of each cycle of CPX-351 until admission for allogeneic stem cell transplant.<br>* Other names: Rydapt;Drug: Busulfan<br>* 0.8 mg/kg/dose every six hours x 12 doses administered intravenously<br>* Other names: Myleran;Drug: Melphalan<br>* 70 mg/m2/day x 2 doses administered intravenously<br>* Other names: Alkeran;Drug: Fludarabine<br>* 25 mg/m2/day x 5 doses administered intravenously<br>* Other names: Fludara;Biological: CD34+ selected allogeneic stem cell transplant from an HLA-compatible donor<br>* Allogeneic stem cell transplant infused intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the complete remission rate | Assess the complete remission rate following induction therapy with CPX-351 plus midostaurin when administered to patients | 3, 6, 12 and 24 months | 
| Change in Progression Free Survival (PFS) | to determine the PFS of these patients following allo SCT. To estimate PFS the Kaplan-Meier method will be used. | 3, 6, 12 and 24 months | 
| Change in Overall Survival (OS) | to determine the OS of these patients following allo SCT. To estimate OS the Kaplan-Meier method will be used. | 3, 6, 12 and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the rate of Minimal Residual Disease (MRD) negativity | Ascertain the rate of MRD negativity by next generation sequencing at sequential time post following induction treatment at complete remission prior to allo Stem Cell Transplantation (SCT) | 3, 6, 12 and 24 months | 
| Correlation of Minimal Residual Disease (MRD) | Correlation of duration of MRD negative status with duration of complete remission of these patients will be assessed using Spearman's correlation with reported p value. | 3, 6, 12 and 24 months |