Leukemia, Myeloid, Acute, Leukemia, Relapsed Adult Acute Myeloid, Myelodysplastic Syndromes, Myelodysplastic Syndromes, Previously Treated
Conditions
Brief summary
This pilot study is designed to evaluate outcomes with the combination of CPX-351 salvage therapy and haplo-cord graft stem cell transplantation for subjects with relapsed or refractory AML or myelodysplastic syndrome.
Interventions
DRUGCPX-351
Salvage Chemotherapy: CPX-351 at 120 u/m2 on Days -21, -19, and -17
DRUGFludarabine
Fludarabine 150 mg/m2 (30 mg/m2/day x 5 days, Day -7 to Day -3)
DRUGMelphalan
Melphalan 140 mg/m2 (Day -2)
DRUGRabbit Anti-Human T-Lymphocyte Globulin
Rabbit ATG (rATG)-thymoglobulin 4.5 mg/kg (1.5 mg/kg/day x 3 days)
BIOLOGICALHaplo-Cord Stem Cell Transplantation
Allogeneic stem cell transplantation using a haploidentical donor and umbilical cord blood unit.
Sponsors
Jazz Pharmaceuticals
Weill Medical College of Cornell University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
1. Subject must have refractory or relapsed Acute Myeloid Leukemia (AML) according to previously established criteria: 1. Primary induction failure (PIF) after ≥ 2 cycles of chemotherapy 2. First relapse 3. Relapse refractory to salvage chemotherapy 4. Second or subsequent relapse 2. Subjects with Myelodysplastic Syndrome (MDS): (a) Either Refractory Anemia with Excess Blasts I or Refractory Anemia with Excess Blasts II (RAEB I or RAEB II) 3. Karnofsky performance status ≥ 70 4. Willing to participate as a research subject and sign an informed consent form 5. Adequate physical function measured by: 1. Cardiac: asymptomatic, or if symptomatic then Left Ventricular Ejection Fraction (LVEF) at rest must be ≥ 45% and must improve with exercise 2. Hepatic: ≤3 x upper limit of normal (ULN) alanine aminotransferase (ALT) and ≤ 1.5 total serum bilirubin, unless liver is involved with the disease or there is congenital benign hyperbilirubinemia 3. Renal: serum creatinine within normal range, or if serum creatinine is outside the normal range, then calculated creatinine clearance ≥ 60 ml/min 4. Pulmonary: asymptomatic, or if symptomatic, diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 45% of predicted (corrected for hemoglobin) 6. If subject has prior malignancy, must be without any evidence of disease of that prior malignancy for at least 2 years (excludes skin cancers that may have been excised within that 2 year period).
Exclusion criteria
1. Serious active or uncontrolled infection or medical condition 2. Women who are pregnant or breast feeding. Women of childbearing age must use adequate contraception and have a negative pregnancy test. 3. Prior daunorubicin therapy with a cumulative dose of more than 368 mg/m2 or equivalent 4. Other systemic anticancer therapy or ongoing clinically relevant toxicities from such therapy (at discretion of the investigator) 5. History of and/or current evidence of myocardial impairment (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, congestive heart failure), resulting in heart failure by New York Heart Association Class III or IV staging. 6. Subjects with Wilson disease or other Copper-related disorders.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 1 year | Evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) |
| Neutrophil Engraftment | 100 days | Evaluate the time to neutrophil engraftment, defined as the first day in which absolute neutrophil count (ANC) \>500/mm3 for three consecutive days |
| Overall Survival at Day 100, 6 months, and 1 year | Day 100, 6 months, and 1 year post-transplant | Evaluate survival of subjects alive, with or without presence of disease, at the designated time points |
| Disease-Free Survival at Day 100, 6 months, and 1 year | Day 100, 6 months, and 1 year post-transplant | Evaluate survival of subjects alive without disease at the designated time points |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-Relapse Mortality | Day 100 | Death that cannot be explained by persistence, relapse, or progression of underlying disease |
| Relapse Rate | Day 100, 6 months, 1 year | Time to first relapse or progression of underlying disease after initiation of protocol therapy |
Countries
United States
Outcome results
None listed