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

• ClinicalTrials.gov Identifier: NCT03393611
• Recruitment Status: Recruiting
• First Posted: January 8, 2018
• Last Update Posted: January 4, 2019
• Sponsor: Weill Medical College of Cornell University
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Leukemia, Relapsed Adult Acute Myeloid; Myelodysplastic Syndromes, Previously Treated	Drug: CPX-351; Drug: Fludarabine; Drug: Melphalan; Drug: Rabbit Anti-Human T-Lymphocyte Globulin; Biological: Haplo-Cord Stem Cell Transplantation	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 30, 2012
• Estimated Primary Completion Date: November 30, 2020
• Estimated Study Completion Date: November 30, 2022

Arms and Interventions

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 Name: Cytarabine:Daunorubicin Liposome Injection; Drug: Fludarabine; Fludarabine 150 mg/m2 (30 mg/m2/day x 5 days, Day -7 to Day -3); Other Name: Fludara; Drug: Melphalan; Melphalan 140 mg/m2 (Day -2); Other Name: 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 Name: Thymoglobulin; Biological: Haplo-Cord Stem Cell Transplantation; Allogeneic stem cell transplantation using a haploidentical donor and umbilical cord blood unit.

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 1 year ]
   Evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
2. Neutrophil Engraftment [ Time Frame: 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
3. Overall Survival at Day 100, 6 months, and 1 year [ Time Frame: 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
4. Disease-Free Survival at Day 100, 6 months, and 1 year [ Time Frame: Day 100, 6 months, and 1 year post-transplant ]
   Evaluate survival of subjects alive without disease at the designated time points

Secondary Outcome Measures :

1. Non-Relapse Mortality [ Time Frame: Day 100 ]
   Death that cannot be explained by persistence, relapse, or progression of underlying disease
2. Relapse Rate [ Time Frame: Day 100, 6 months, 1 year ]
   Time to first relapse or progression of underlying disease after initiation of protocol therapy

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Ashlee Torres, RN; 212-746-7117; ant9105@med.cornell.edu

Contact: Usama Gergis, MD; 646-962-7950; usg2001@med.cornell.edu

Locations

United States, New York

Weill Cornell Medical College; Recruiting

New York, New York, United States, 10021

Contact: Ashlee Torres, RN 212-746-7117 ant9105@med.cornell.edu

Contact: Usama Gergis, MD 646-962-7950 usg2001@med.cornell.edu

Principal Investigator: Usama Gergis, MD

Sub-Investigator: Koen van Besien, MD

Sub-Investigator: Tsiporah B Shore, MD

Sub-Investigator: Sebastian A Mayer, MD

Sub-Investigator: Adrienne Phillips, MD

Sub-Investigator: Jingmei Hsu, MD

Sub-Investigator: Jeffrey E Ball, MD

Sub-Investigator: Pinkal Desai, MD

Sub-Investigator: Sangmin Lee, MD

Sub-Investigator: Ellen K Ritchie, MD

Sub-Investigator: Michael S Samuel, MD

Sub-Investigator: Gail J Roboz, MD

Sponsors and Collaborators

Weill Medical College of Cornell University

Investigators

• Principal Investigator: Usama Gergis, MD; Weill Medical College of Cornell University

More Information

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT03393611
• Other Study ID Numbers: 1107011830
• First Posted: January 8, 2018
• Last Update Posted: January 4, 2019
• Last Verified: January 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Syndrome; Disease; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Fludarabine; Fludarabine phosphate; Melphalan; Thymoglobulin; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists