Acute Myeloid Leukemia
Conditions
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.
Interventions
DRUGCPX-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.
DRUGMidostaurin
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.
DRUGBusulfan
0.8 mg/kg/dose every six hours x 12 doses administered intravenously
DRUGMelphalan
70 mg/m2/day x 2 doses administered intravenously
DRUGFludarabine
25 mg/m2/day x 5 doses administered intravenously
BIOLOGICALCD34+ selected allogeneic stem cell transplant from an HLA-compatible donor
Allogeneic stem cell transplant infused intravenously
Sponsors
Jazz Pharmaceuticals
Guenther Koehne
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed