Induction Therapy for Patients With FLT3 Mutated Acute Myeloid Leukemia

Sponsor

Baptist Health South Florida (Other)

Overall Status

Recruiting

CT.gov ID

NCT04982354

Collaborator

Jazz Pharmaceuticals (Industry)

Enrollment

Location

Arm

120.9

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: CPX-351 Drug: Midostaurin Drug: Busulfan Drug: Melphalan Drug: Fludarabine Biological: CD34+ selected allogeneic stem cell transplant from an HLA-compatible donor	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 5, 2022

Anticipated Primary Completion Date :

Aug 1, 2031

Anticipated Study Completion Date :

Aug 1, 2032

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Investigational Treatment 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 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. Drug: Midostaurin 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. Other Names: Rydapt Drug: Busulfan 0.8 mg/kg/dose every six hours x 12 doses administered intravenously Other Names: Myleran Drug: Melphalan 70 mg/m2/day x 2 doses administered intravenously Other Names: Alkeran Drug: Fludarabine 25 mg/m2/day x 5 doses administered intravenously Other Names: Fludara Biological: CD34+ selected allogeneic stem cell transplant from an HLA-compatible donor Allogeneic stem cell transplant infused intravenously

Arm

Intervention/Treatment

Experimental: Investigational Treatment

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

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.

Drug: Midostaurin

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.

Other Names:

Rydapt

Drug: Busulfan

0.8 mg/kg/dose every six hours x 12 doses administered intravenously

Other Names:

Myleran

Drug: Melphalan

70 mg/m2/day x 2 doses administered intravenously

Other Names:

Alkeran

Drug: Fludarabine

25 mg/m2/day x 5 doses administered intravenously

Other Names:

Fludara

Biological: CD34+ selected allogeneic stem cell transplant from an HLA-compatible donor

Allogeneic stem cell transplant infused intravenously

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Change in the rate of Minimal Residual Disease (MRD) negativity [3, 6, 12 and 24 months]
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)
Correlation of Minimal Residual Disease (MRD) [3, 6, 12 and 24 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).