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

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ClinicalTrials.gov Identifier: NCT03393611
Recruitment Status : Recruiting
First Posted : January 8, 2018
Last Update Posted : January 8, 2018
Sponsor:
Information provided by (Responsible Party):

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, 2019
Estimated Study Completion Date : November 30, 2021


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

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03393611


Contacts
Contact: Jennifer Bourle, RN 212-746-2844 jeb9097@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: Jennifer Bourke, RN    212-746-2844    jeb9097@med.cornell.edi   
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 Shore, MD         
Sub-Investigator: Sebastian Mayer, 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     History of Changes
Other Study ID Numbers: 1107011830
First Posted: January 8, 2018    Key Record Dates
Last Update Posted: January 8, 2018
Last Verified: January 2018

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

Additional relevant MeSH terms:
Syndrome
Leukemia
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Fludarabine
Fludarabine phosphate
Melphalan
Daunorubicin
Thymoglobulin
Antilymphocyte Serum
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
Antibiotics, Antineoplastic