Induction Therapy for Patients With FLT3 Mutated Acute Myeloid Leukemia

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: CPX-351; Drug: Midostaurin; Drug: Busulfan; Drug: Melphalan; Drug: Fludarabine; Biological: CD34+ selected allogeneic stem cell transplant from an HLA-compatible donor

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Guenther Koehne, MD, PhD; Phone Number: 786-596-2000; Email: GuentherK@Baptisthealth.net

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33176
      • Recruiting
      • Miami Cancer Institute at Baptist Health of South Florida
      • Principal Investigator: Guenther Koehne, MD, PhD
      • Contact: Guenther Koehne, MD, PhD; Phone Number: 786-596-2000; Email: GuentherK@Baptisthealth.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Guenther Koehne
• Collaborators: Jazz Pharmaceuticals
• Investigators: Principal Investigator: Guenther Koehne, MD. PhD, Miami Cancer Institute at Baptist Health of South Florida

Publications and helpful links

Helpful Links

• Miami Cancer Institute Website

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Estimated): August 1, 2031
• Study Completion (Estimated): August 1, 2032

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 28, 2021
• First Posted (Actual): July 29, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Protein Kinase Inhibitors; Melphalan; Fludarabine; Busulfan; Midostaurin
• Other Study ID Numbers: 2019-KOE-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No