Induction Therapy for Patients With FLT3 Mutated Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04982354
• Other study ID #: 2019-KOE-003
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 5, 2022
• Est. completion date: August 1, 2032

Study information

• Verified date: April 2024
• Source: Baptist Health South Florida
• Contact: Guenther Koehne, MD, PhD
• Phone: 786-596-2000
• Email: GuentherK[@]Baptisthealth.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 1, 2032
• Est. primary completion date: August 1, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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).

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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.
• 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.
• Busulfan
0.8 mg/kg/dose every six hours x 12 doses administered intravenously
• Melphalan
70 mg/m2/day x 2 doses administered intravenously
• Fludarabine
25 mg/m2/day x 5 doses administered intravenously

Biological:
• CD34+ selected allogeneic stem cell transplant from an HLA-compatible donor
Allogeneic stem cell transplant infused intravenously

Locations

Country	Name	City	State
United States	Miami Cancer Institute at Baptist Health of South Florida	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Guenther Koehne	Jazz Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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

External Links

•   Miami Cancer Institute Website