Clinical Trials /

CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

NCT02019069

Description:

This phase 2 clinical trial studies how well CPX-351 (liposomal cytarabine-daunorubicin) works in treating patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. Drugs used in chemotherapy, such as CPX-351, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

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

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
  • Official Title: A Phase II Study of CPX-351 for Treatment of AML or Higher Risk MDS Relapsed or Refractory to Prior Therapy With Hypomethylating (HMA) Agent

Clinical Trial IDs

  • ORG STUDY ID: HEM0036
  • SECONDARY ID: NCI-2013-01982
  • SECONDARY ID: 4593
  • SECONDARY ID: HEM0036
  • SECONDARY ID: P30CA124435
  • SECONDARY ID: 28524
  • NCT ID: NCT02019069

Conditions

  • Adult Acute Erythroid Leukemia (M6)
  • Adult Acute Megakaryoblastic Leukemia (M7)
  • Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5)
  • Adult Acute Myeloblastic Leukemia With Maturation (M2)
  • Adult Acute Myeloblastic Leukemia Without Maturation (M1)
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Adult Acute Myelomonocytic Leukemia (M4)
  • de Novo Myelodysplastic Syndromes
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult Acute Myeloid Leukemia
  • Secondary Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
liposomal cytarabine-daunorubicin CPX-351CPX-351Treatment (liposomal cytarabine-daunorubicin CPX-351)

Purpose

This phase II clinical trial studies how well liposomal cytarabine-daunorubicin CPX-351 (CPX-351) works in treating patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. Drugs used in chemotherapy, such as liposomal cytarabine-daunorubicin CPX-35, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Determine the efficacy and safety profile of the use of CPX-351 in older patients (age 60
      and older) with: higher risk of myelodysplastic syndrome (MDS) who are refractory/relapsed
      after prior hypomethylating (HMA) therapy; subjects greater than 75 years old with higher
      risk MDS who are HMA relapsed/refractory who have progressed to acute myeloid leukemia
      (AML)); AML with refractory/relapsed disease after prior HMA therapy for AML.

      SECONDARY OBJECTIVES:

      I. Determine the duration of remission following induction therapy with CPX-351.

      II. Determine overall survival at 12 months. III. Determine the early induction mortality (at
      60 days) following CPX-351 in this cohort following induction therapy.

      OUTLINE:

      INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) over
      90 minutes on days 1, 3, and 5. Patients with reduced blast count not achieving a
      morphological leukemia free state (< 5% blasts) receive a second course of induction therapy.
      Patients achieving a complete remission (CR) or a CR with incomplete blood count recovery
      (CRi) at day 14 or after a second course of induction therapy proceed to consolidation
      therapy.

      SECOND INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV over 90
      minutes on days 1 and 3.

      CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin
      CPX-351 IV over 90 minutes on days 1 and 3. Patients may receive a second course after 28-75
      days in the absence of disease progression or unacceptable toxicity.

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

Trial Arms

NameTypeDescriptionInterventions
Treatment (liposomal cytarabine-daunorubicin CPX-351)ExperimentalINDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients achieving a complete remission (CR) or a CR with incomplete blood count recovery (CRi) at day 14 proceed to consolidation therapy. Patients with reduced blast count not achieving a morphological leukemia free state (< 5% blasts) receive a second course of induction therapy liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Patients achieving a CR or a CRi at day 14 or after a second course of induction therapy proceed to consolidation therapy. SECOND INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment may repeat after 28-75 days in the absence of disease progression or unacceptable toxicity.
  • liposomal cytarabine-daunorubicin CPX-351

Eligibility Criteria

        Inclusion Criteria:

          -  Ability to understand and voluntarily give informed consent

          -  Age ≥ 60

          -  Pathological diagnosis of AML (by WHO criteria) or higher risk MDS (includes int-2 and
             high risk MDS by IPSS) along with one of the following:

               -  Patients with de novo or secondary MDS with progression/refractoriness after HMA
                  treatment who have not transformed to AML

               -  Patients with MDS and prior HMA treatment for MDS who transform to AML

               -  Patients with AML who are refractory/relapsed after HMA therapy for their AML are
                  eligible

          -  Life expectancy > 1 month

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Able to adhere to the study visit schedule and other protocol requirements

          -  Laboratory values fulfilling the following:

               -  Serum creatinine < 2.0 mg/dL

               -  Serum total bilirubin ≤ 2.5 mg/dL. Note, patients with Gilbert's syndrome may
                  have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients
                  with Gilbert's syndrome are included if their total bilirubin is ≤ 2 times their
                  baseline total bilirubin.

               -  Serum alanine aminotransferase or aspartate aminotransferase < 3 times ULN

          -  Cardiac ejection fraction ≥ 45% by echocardiography (transthoracic echocardiography)
             or MUGA scan

          -  Patients with second malignancies may be eligible at discretion of PI given acute life
             threatening nature of untreated AML or higher risk MDS. Patients maintained on
             long-term non-chemotherapy treatment, e.g., hormonal therapy, are also eligible.

        Exclusion Criteria:

          -  Patients who have previously undergone allogeneic hematopoietic stem cell transplant
             will be excluded from this study

          -  Patients who have previously had > 368 mg/m2 cumulative dose of daunorubicin or > 368
             mg/m2 daunorubicin-equivalent anthracycline therapy (for example, from prior treatment
             of solid tumors). See appendix for anthracycline equivalence table.

          -  Acute promyelocytic leukemia [t(15;17)]

          -  Any serious medical condition, laboratory abnormality or psychiatric illness that
             would prevent obtaining informed consent

          -  Patients who have had conventional intensive cytotoxic induction chemotherapy for
             treatment of specifically MDS or AML are excluded.

          -  Patients who have not previously been treated with HMA therapy will be excluded

          -  Clinical evidence of active CNS leukemia

          -  Patients with evidence of uncontrolled current myocardial impairment (e.g. unstable
             ischemic heart disease, uncontrolled arrhythmia, symptomatic valvular dysfunction not
             controlled on medical therapy, uncontrolled hypertensive heart disease, and
             uncontrolled congestive heart failure)

          -  Active and uncontrolled infection. Patients with an active infection receiving
             treatment and hemodynamically stable for 48 hours may be entered into the study

          -  Known active uncontrolled HIV or hepatitis C infection

          -  Known hypersensitivity to cytarabine, daunorubicin or liposomal products

          -  Known history of Wilson's disease or other copper-related disorders

          -  Other medical or psychiatric illness or organ dysfunction or laboratory abnormality
             which in the opinion of the investigator would compromise the patient's safety or
             interfere with data interpretation

          -  Laboratory abnormalities:

               -  Serum creatinine ≥ 2.0 mg/dL

               -  Serum total bilirubin > 2.5 mg/dL. Note, patients with Gilbert's syndrome may
                  have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients
                  with Gilbert's syndrome are excluded if their total bilirubin is > 2 times their
                  baseline total bilirubin.

               -  Serum alanine aminotransferase or aspartate aminotransferase > 3 times ULN
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of mortality assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame:At day 30
Safety Issue:
Description:To analyze the safety data, adverse events recorded using CTCAE 4.0 for each patient will reviewed and totaled, for the total number of adverse events for each adverse event compared to total group of patients (rate of outcome of each adverse event in study population).

Secondary Outcome Measures

Measure:Duration of remission following induction with CPX-351
Time Frame:From the start of response until disease relapse or death, assessed up to 1 year
Safety Issue:
Description:Calculated by counting the number of days from the date of remission until date of disease relapse for patients who achieve a CR (and CRi for AML). The average days of remission will be calculated to determine the median duration of remission.
Measure:Overall survival
Time Frame:From the date of entry into trial to death from any cause, assessed at 12 months
Safety Issue:
Description:Determined by the number of patients who are alive at 12 months compared to the number of patients who initiated into the study.
Measure:Early induction mortality after first induction
Time Frame:Day 60
Safety Issue:
Description:Calculated by determining the number of deaths within the first 60 days, using day 1 of the first induction therapy as the first day, compared to the total number of patients who have received any dose of CPX-351.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Rondeep Brar

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