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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 87 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CPX-351 Salvage Therapy and Transplant; 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; Salvage Chemotherapy: CPX-351 at 120 u/m2 on Days -21, -19, and -17; Other Names: Cytarabine:Daunorubicin Liposome Injection; Drug: Fludarabine; Fludarabine 150 mg/m2 (30 mg/m2/day x 5 days, Day -7 to Day -3); Other Names: Fludara; Drug: Melphalan; Melphalan 140 mg/m2 (Day -2); Other Names: Alkeran; Drug: Rabbit Anti-Human T-Lymphocyte Globulin; Rabbit ATG (rATG)-thymoglobulin 4.5 mg/kg (1.5 mg/kg/day x 3 days); Other Names: Thymoglobulin; Biological: Haplo-Cord Stem Cell Transplantation; Allogeneic stem cell transplantation using a haploidentical donor and umbilical cord blood unit.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Jazz Pharmaceuticals
• Investigators: Principal Investigator: Sebastian Mayer, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2012
• Primary Completion (Actual): August 30, 2021
• Study Completion (Actual): November 18, 2021

Study Registration Dates

• First Submitted: December 7, 2017
• First Submitted That Met QC Criteria: January 2, 2018
• First Posted (Actual): January 8, 2018

Study Record Updates

• Last Update Posted (Estimate): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Melphalan; Fludarabine; Cytarabine; Daunorubicin; Thymoglobulin
• Other Study ID Numbers: 1107011830

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No