Clinical Trials /

Liposomal Cytarabine-Daunorubicin CPX-351 in Treating Patients With Untreated Myelodysplastic Syndrome or Acute Myeloid Leukemia

NCT01804101

Description:

This randomized clinical trial studies liposomal cytarabine-daunorubicin CPX-351 in treating patients with untreated myelodysplastic syndrome or acute myeloid leukemia. Drugs used in chemotherapy, such as liposomal cytarabine-daunorubicin CPX-351, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Completed

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Liposomal Cytarabine-Daunorubicin CPX-351 in Treating Patients With Untreated Myelodysplastic Syndrome or Acute Myeloid Leukemia
  • Official Title: Liposomal Cytarabine and Daunorubicin (CPX-351) for Adults With Untreated High-Risk MDS and Non-APL AML at High Risk of Treatment-Related Mortality

Clinical Trial IDs

  • ORG STUDY ID: 2642.00
  • SECONDARY ID: NCI-2013-00481
  • SECONDARY ID: 2642
  • SECONDARY ID: 2642.00
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT01804101

Conditions

  • Acute Biphenotypic Leukemia
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome
  • Untreated Adult Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Liposomal Cytarabine-Daunorubicin CPX-351CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351Arm I (lower-dose liposomal cytarabine-daunorubicin CPX-351)

Purpose

This randomized clinical trial studies liposomal cytarabine-daunorubicin CPX-351 in treating patients with untreated myelodysplastic syndrome or acute myeloid leukemia. Drugs used in chemotherapy, such as liposomal cytarabine-daunorubicin CPX-351, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Estimate whether the 32 units/m^2 or the 64 units/m^2 or both dose levels of CPX-351
      (liposomal cytarabine-daunorubicin CPX-351) are likely to improve treatment-related mortality
      (TRM) rate while keeping the complete remission (CR) rate constant in patients with untreated
      high-risk myelodysplastic syndrome (MDS) or non-acute promyelocytic leukemia (APL) acute
      myeloid leukemia (AML) at high risk of TRM.

      SECONDARY OBJECTIVES:

      I. Describe the CR/CR with incomplete platelet count recovery (CRp) rate after up to 4 cycles
      of induction/re-induction therapy.

      II. Describe the event-free survival, disease-free survival, and overall survival of patients
      who achieve CR/CRp.

      III. Estimate the frequency and severity of regimen-associated toxicities.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I:

      INDUCTION/RE-INDUCTION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351
      intravenously (IV) over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4
      courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR
      or CRp continue on to consolidation.

      CONSOLIDATION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over
      90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of
      disease progression or unacceptable toxicity.

      ARM II: (closed to accrual effective 4/21/14) INDUCTION/RE-INDUCTION: Patients receive
      higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5.
      Treatment repeats every 40 days for 4 courses in the absence of disease progression or
      unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation.

      CONSOLIDATION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over
      90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 1 month.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (lower-dose liposomal cytarabine-daunorubicin CPX-351)ExperimentalINDUCTION/RE-INDUCTION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation. CONSOLIDATION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  • Liposomal Cytarabine-Daunorubicin CPX-351
Arm II (closed to accrual effective 4/21/14)ExperimentalINDUCTION/RE-INDUCTION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation. CONSOLIDATION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity.
  • Liposomal Cytarabine-Daunorubicin CPX-351

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of untreated "high-risk" MDS (>= 10% blasts) or AML other than acute
             promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008
             World Health Organization (WHO) classification; patients with biphenotypic AML are
             eligible; outside diagnostic material is acceptable as long as peripheral blood and/or
             bone marrow slides are reviewed at the study institution and cytogenetic/molecular
             information is available

               -  Prior hydroxyurea for AML is permitted but should be discontinued prior to start
                  of CPX-351 treatment

               -  Azacitidine, decitabine, lenalidomide, and growth factors are permitted for
                  low-risk MDS (< 10% blasts); all treatments for MDS should be discontinued prior
                  to start of CPX-351 treatment

          -  Treatment-related mortality (TRM) score >= 13.1 as calculated with simplified model

          -  Bilirubin < 2.0 mg/mL x upper limit of normal; this requirement reflects the excretion
             of CPX-351 by the liver

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 4.0 x upper limit of
             normal; this requirement reflects the excretion of CPX-351 by the liver

          -  Left ventricular ejection fraction (LVEF) >= 40%, assessed within 28 days prior to
             registration, e.g. by multi gated acquisition (MUGA) scan or echocardiography, or
             other appropriate diagnostic modality

          -  Patients with symptoms/signs of hyperleukocytosis or white blood cell (WBC) >
             100,000/uL can be treated with leukapheresis prior to enrollment

          -  Provide signed written informed consent

        Exclusion Criteria:

          -  Refractory/relapsing blast crisis of chronic myelogenous leukemia (CML)

          -  Concomitant illness associated with a likely survival of < 1 year

          -  Active systemic fungal, bacterial, viral, or other infection, unless under treatment
             with anti-microbials and controlled/stable, as defined as being afebrile and
             hemodynamically stable for 24-48 hours
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment-related Mortality Rate. (TRM)
Time Frame:Up to 1 month after completion of study treatment
Safety Issue:
Description:Estimate whether the 32 units/m2 or the 64 units/m2 or both dose levels of CPX-351 are likely to improve treatment-related mortality (TRM) rate while keeping the CR rate constant in patients with untreated high-risk MDS or non-APL AML at high risk of TRM.

Secondary Outcome Measures

Measure:Overall Remission Rate (CR+CRp)
Time Frame:Up to day 28
Safety Issue:
Description:Overall Remission Rate for the CR/CR with incomplete platelet count recovery (CRp) rate after up to 4 cycles of induction/re-induction therapy.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Fred Hutchinson Cancer Research Center

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