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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03393611
Recruitment Status : Active, not recruiting
First Posted : January 8, 2018
Last Update Posted : January 27, 2022
Jazz Pharmaceuticals
Information provided by (Responsible Party):
Weill Medical College of Cornell University

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
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
Actual Primary Completion Date : August 30, 2021
Estimated Study Completion Date : November 30, 2022

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.

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT03393611

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United States, New York
Weill Cornell Medical College
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
Jazz Pharmaceuticals
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Principal Investigator: Koen van Besien, MD, PhD Weill Medical College of Cornell University
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Responsible Party: Weill Medical College of Cornell University Identifier: NCT03393611    
Other Study ID Numbers: 1107011830
First Posted: January 8, 2018    Key Record Dates
Last Update Posted: January 27, 2022
Last Verified: January 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists