Induction Therapy for Patients With FLT3 Mutated Acute Myeloid Leukemia

NCT04982354 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 2019-KOE-003
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Change in the rate of Minimal Residual Disease (MRD) negativity

  3, 6, 12 and 24 months

• Correlation of Minimal Residual Disease (MRD)

  3, 6, 12 and 24 months

Study Arms (1)

Investigational Treatment

EXPERIMENTAL

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; Drug: Midostaurin; Drug: Busulfan; Drug: Melphalan; Drug: Fludarabine; Biological: CD34+ selected allogeneic stem cell transplant from an HLA-compatible donor

Interventions

CPX-351 DRUG

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.

Investigational Treatment

Midostaurin DRUG

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.

Also known as: Rydapt

Investigational Treatment

Busulfan DRUG

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

Also known as: Myleran

Investigational Treatment

Melphalan DRUG

70 mg/m2/day x 2 doses administered intravenously

Also known as: Alkeran

Investigational Treatment

Fludarabine DRUG

25 mg/m2/day x 5 doses administered intravenously

Also known as: Fludara

Investigational Treatment

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

Allogeneic stem cell transplant infused intravenously

Investigational Treatment

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a Karnofsky (adult) Performance Status of at least 70%.
• Patients must have adequate organ function

You may not qualify if:

• 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).

Sponsors & Collaborators

• Guenther Koehne: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

Miami Cancer Institute at Baptist Health of South Florida

Miami, Florida, 33176, United States

Location

Related Links

• Miami Cancer Institute Website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

CPX-351; midostaurin; Busulfan; Melphalan; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Guenther Koehne, MD. PhD

  Miami Cancer Institute at Baptist Health of South Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director and Chief of Blood and Marrow Transplant, Hematologic Oncology and Benign Hematology

Study Record Dates

• First Submitted: July 13, 2021
• First Posted: July 29, 2021
• Study Start: July 5, 2022
• Primary Completion (Estimated): August 1, 2031
• Study Completion (Estimated): August 1, 2032
• Last Updated: October 1, 2024

Record last verified: 2024-09

Locations

US (1)