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

NCT03393611 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 1107011830
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• Non-Relapse Mortality

  Day 100

• Relapse Rate

  Day 100, 6 months, 1 year

Study Arms (1)

CPX-351 Salvage Therapy and Transplant

EXPERIMENTAL

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; Drug: Fludarabine; Drug: Melphalan; Drug: Rabbit Anti-Human T-Lymphocyte Globulin; Biological: Haplo-Cord Stem Cell Transplantation

Interventions

CPX-351 DRUG

Salvage Chemotherapy: CPX-351 at 120 u/m2 on Days -21, -19, and -17

Also known as: Cytarabine:Daunorubicin Liposome Injection

CPX-351 Salvage Therapy and Transplant

Fludarabine DRUG

Fludarabine 150 mg/m2 (30 mg/m2/day x 5 days, Day -7 to Day -3)

Also known as: Fludara

CPX-351 Salvage Therapy and Transplant

Melphalan DRUG

Melphalan 140 mg/m2 (Day -2)

Also known as: Alkeran

CPX-351 Salvage Therapy and Transplant

Rabbit Anti-Human T-Lymphocyte Globulin DRUG

Rabbit ATG (rATG)-thymoglobulin 4.5 mg/kg (1.5 mg/kg/day x 3 days)

Also known as: Thymoglobulin

CPX-351 Salvage Therapy and Transplant

Haplo-Cord Stem Cell Transplantation BIOLOGICAL

Allogeneic stem cell transplantation using a haploidentical donor and umbilical cord blood unit.

CPX-351 Salvage Therapy and Transplant

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Leukemia

Interventions

CPX-351; fludarabine; fludarabine phosphate; Melphalan; Antilymphocyte Serum; thymoglobulin

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Officials

• Sebastian Mayer, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: January 8, 2018
• Study Start: November 30, 2012
• Primary Completion: August 30, 2021
• Study Completion: November 18, 2021
• Last Updated: December 21, 2022

Record last verified: 2022-12

Locations

US (1)