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

Phase 1

Completed

• Conditions: Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Leukemia, Relapsed Adult Acute Myeloid; Myelodysplastic Syndromes, Previously Treated
• Interventions: Drug: CPX-351; Drug: Fludarabine; Drug: Melphalan; Drug: Rabbit Anti-Human T-Lymphocyte Globulin; Biological: Haplo-Cord Stem Cell Transplantation

• Registration Number: NCT03393611
• Lead Sponsor: Weill Medical College of Cornell University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-11-30
• Study First Submitted: 2017-12-07
• Study First Submitted QC: 2018-01-02
• Study First Posted: 2018-01-08
• Primary Completion: 2021-08-30
• Study Completion: 2021-11-18
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-19
• Last Update Posted: 2022-12-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CPX-351 Salvage Therapy and Transplant	CPX-351	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.
CPX-351 Salvage Therapy and Transplant	Rabbit Anti-Human T-Lymphocyte Globulin	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.
CPX-351 Salvage Therapy and Transplant	Haplo-Cord Stem Cell Transplantation	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.
CPX-351 Salvage Therapy and Transplant	Fludarabine	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.
CPX-351 Salvage Therapy and Transplant	Melphalan	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.

Primary Outcome Measures

Name	Time	Method
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
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)
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Weill Cornell Medical College; 🇺🇸 New York, New York, United States