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

Myelodysplastic Syndromes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03393611
• Other study ID #: 1107011830
• Status: Completed
• Phase: Phase 1
• Start date: November 30, 2012
• Est. completion date: November 18, 2021

Study information

• Verified date: December 2022
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: November 18, 2021
• Est. primary completion date: August 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Relapsed Adult Acute Myeloid
• Myelodysplastic Syndromes
• Myelodysplastic Syndromes, Previously Treated
• Preleukemia
• Syndrome

Intervention

Drug:
• CPX-351
Salvage Chemotherapy: CPX-351 at 120 u/m2 on Days -21, -19, and -17
• Fludarabine
Fludarabine 150 mg/m2 (30 mg/m2/day x 5 days, Day -7 to Day -3)
• Melphalan
Melphalan 140 mg/m2 (Day -2)
• Rabbit Anti-Human T-Lymphocyte Globulin
Rabbit ATG (rATG)-thymoglobulin 4.5 mg/kg (1.5 mg/kg/day x 3 days)

Biological:
• Haplo-Cord Stem Cell Transplantation
Allogeneic stem cell transplantation using a haploidentical donor and umbilical cord blood unit.

Locations

Country	Name	City	State
United States	Weill Cornell Medical College	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Jazz Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Non-Relapse Mortality	Death that cannot be explained by persistence, relapse, or progression of underlying disease	Day 100
Secondary	Relapse Rate	Time to first relapse or progression of underlying disease after initiation of protocol therapy	Day 100, 6 months, 1 year