CPX-351 Salvage Therapy Followed by Haplo-Cord Transplant for Relapsed/Refractory Leukemia or Myelodysplastic Syndrome

Study Overview
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Brief Summary
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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.

Official Title
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A Pilot Study of a Novel Sequential Treatment Utilizing CPX-351 as Salvage Chemotherapy Followed by Allogeneic Stem-Cell Transplantation (SCT) Utilizing a Haplo-cord Graft for Patients With Relapsed or Refractory Leukemia or Myelodysplastic Syndrome

Conditions
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Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Leukemia, Relapsed Adult Acute Myeloid, Myelodysplastic Syndromes, Previously Treated

Intervention / Treatment
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* Drug: CPX-351
* Drug: Fludarabine
* Drug: Melphalan
* Drug: Rabbit Anti-Human T-Lymphocyte Globulin
* Biological: Haplo-Cord Stem Cell Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must have refractory or relapsed Acute Myeloid Leukemia (AML) according to previously established criteria: Primary induction failure (PIF) after ≥ 2 cycles of chemotherapy First relapse Relapse refractory to salvage chemotherapy Second or subsequent relapse 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) Karnofsky performance status ≥ 70 Willing to participate as a research subject and sign an informed consent form Adequate physical function measured by: Cardiac: asymptomatic, or if symptomatic then Left Ventricular Ejection Fraction (LVEF) at rest must be ≥ 45% and must improve with exercise 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 Renal: serum creatinine within normal range, or if serum creatinine is outside the normal range, then calculated creatinine clearance ≥ 60 ml/min Pulmonary: asymptomatic, or if symptomatic, diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 45% of predicted (corrected for hemoglobin) 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: Serious active or uncontrolled infection or medical condition Women who are pregnant or breast feeding. Women of childbearing age must use adequate contraception and have a negative pregnancy test. Prior daunorubicin therapy with a cumulative dose of more than 368 mg/m2 or equivalent Other systemic anticancer therapy or ongoing clinically relevant toxicities from such therapy (at discretion of the investigator) 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. Subjects with Wilson disease or other Copper-related disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPX-351 Salvage Therapy and Transplant<br>Subjects will receive CPX-351 salvage chemotherapy on Day -21, -19, and -17 as a bridge to allogeneic stem cell transplantation using a Fludarabine/Melphalan/rATG conditioning regimen and a haplo-cord graft. | Drug: CPX-351<br>* Salvage Chemotherapy: CPX-351 at 120 u/m2 on Days -21, -19, and -17<br>* Other names: Cytarabine:Daunorubicin Liposome Injection;Drug: Fludarabine<br>* Fludarabine 150 mg/m2 (30 mg/m2/day x 5 days, Day -7 to Day -3)<br>* Other names: Fludara;Drug: Melphalan<br>* Melphalan 140 mg/m2 (Day -2)<br>* Other names: Alkeran;Drug: Rabbit Anti-Human T-Lymphocyte Globulin<br>* Rabbit ATG (rATG)-thymoglobulin 4.5 mg/kg (1.5 mg/kg/day x 3 days)<br>* Other names: Thymoglobulin;Biological: Haplo-Cord Stem Cell Transplantation<br>* Allogeneic stem cell transplantation using a haploidentical donor and umbilical cord blood unit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) | 1 year | 
| Neutrophil Engraftment | Evaluate the time to neutrophil engraftment, defined as the first day in which absolute neutrophil count (ANC) >500/mm3 for three consecutive days | 100 days | 
| Overall Survival at Day 100, 6 months, and 1 year | Evaluate survival of subjects alive, with or without presence of disease, at the designated time points | Day 100, 6 months, and 1 year post-transplant | 
| Disease-Free Survival at Day 100, 6 months, and 1 year | Evaluate survival of subjects alive without disease at the designated time points | Day 100, 6 months, and 1 year post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-Relapse Mortality | Death that cannot be explained by persistence, relapse, or progression of underlying disease | Day 100 | 
| Relapse Rate | Time to first relapse or progression of underlying disease after initiation of protocol therapy | Day 100, 6 months, 1 year |