Clinical Trials /

S0919 Idarubicin, Cytarabine, and Pravastatin in Treating Patients With Relapsed Acute Myeloid Leukemia

NCT00840177

Description:

RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Pravastatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Pravastatin may also help idarubicin and cytarabine work better by making cancer cells more sensitive to the drugs. Giving idarubicin and cytarabine together with pravastatin may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving idarubicin and cytarabine together with pravastatin works in treating patients with relapsed acute myeloid leukemia.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: S0919 Idarubicin, Cytarabine, and Pravastatin in Treating Patients With Relapsed Acute Myeloid Leukemia
  • Official Title: S0919, A Phase II Study of Idarubicin and Ara-C in Combination With Pravastatin for Relapsed Acute Myelogenous Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: S0919
  • SECONDARY ID: S0919
  • SECONDARY ID: U10CA032102
  • SECONDARY ID: NCI-2009-01183
  • NCT ID: NCT00840177

Conditions

  • Leukemia

Interventions

DrugSynonymsArms
cytarabinetreatment
idarubicintreatment
pravastatin sodiumtreatment

Purpose

RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Pravastatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Pravastatin may also help idarubicin and cytarabine work better by making cancer cells more sensitive to the drugs. Giving idarubicin and cytarabine together with pravastatin may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving idarubicin and cytarabine together with pravastatin works in treating patients with relapsed acute myeloid leukemia.

Detailed Description

      OBJECTIVES:

        -  To test whether the complete remission (CR) rate (including CR with incomplete recovery)
           in patients with relapsed acute myeloid leukemia treated with idarubicin and cytarabine
           in combination with pravastatin is sufficiently high to warrant a phase III
           investigation.

        -  To estimate relapse-free survival and overall survival rates in these patients.

        -  To estimate the frequency and severity of toxicities of this regimen in these patients.

        -  To evaluate, in a preliminary manner, whether pre-study cytogenetic features correlate
           with response in these patients.

      OUTLINE: This is a multicenter study.

        -  Induction therapy: Patients receive oral pravastatin once daily on days 1-8, idarubicin
           IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Patients
           achieving complete remission proceed to consolidation therapy.

        -  Consolidation therapy: Beginning 30-60 days after the start of induction therapy,
           patients receive oral pravastatin once daily on days 1-6 and idarubicin IV over 10-15
           minutes and cytarabine IV continuously on days 4 and 5. Treatment repeats approximately
           every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable
           toxicity.

      After completion of study treatment, patients are followed periodically for 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
treatmentExperimentalInduction (1 cycle): pravastatin 1280 mg/d PO D 1-8 idarubicin 12 mg/m2/d IV D 4-6 AraC 1.5 g/m2/d contIV D 4-7 Consolidation (up to 2 cycles): pravastatin 1280 mg/d PO D 1-6 idarubicin 12 mg/m2/d IV D 4-5 AraC 1.5 g/m2/d contIV D 4-5
  • cytarabine
  • idarubicin
  • pravastatin sodium

Eligibility Criteria

        Cohort 1 (MDS transformed to AML) is open to accrual

        Cohort 2 (relapsed/refractory AML) is permanently closed to accrual

        DISEASE CHARACTERISTICS:

          -  For patients registered to relapsed/refractory (Cohort 2), morphologically confirmed
             diagnosis of acute myeloid leukemia (AML)

          -  Patient registered to the MDS transformed to AML cohort (Cohort 1) patients must have
             a previous morphologically confirmed diagnosis of MDS/CMML. Patients may have received
             previous non-intensive therapy (such as: azacitadine, decitabine, low-dose cytarabine,
             lenalidomide) given treatment of MDS/CMML (with up to 20% blasts). At time of
             registration, patient must have morphologically confirmed diagnosis of AML.

          -  Patients with acute promyelocytic leukemia (i.e., APL, FAB M3) or blastic
             transformation of chronic myelogenous leukemia are not eligible

          -  Patients mus not have received autologous or allogeneic stem cell transplant.

          -  Patients in the relapsed/refractory AML cohort (Cohort 2) must:

               -  Have received ≥ 1 prior chemotherapy regimen for AML

                    -  Any type of prior chemotherapy allowed

                    -  Administration of hydroxyurea to control high WBC prior to, during, and
                       after registration is permitted

               -  Relapse must be documented by a bone marrow examination demonstrating > 5% blasts
                  in the bone marrow not attributable to another cause

               -  Patient must not have received chemo within 14 days prior to registration

          -  Primary refractory patients eligible if, on Day 14 of previous chemo regimen, they
             have significant residual disease. Patients who received only hypomethylating agent or
             low dose therapy for Induction are not considered primary refractory for this study
             and are not eligible.

          -  Relapsed patients must have achieved a complete remission (CR) or CR with incomplete
             blood count recovery that lasted < 6 months after the last induction regimen

          -  No clinical evidence of leptomeningeal disease

          -  Pretreatment (collected within 28 days of registration) cytogenetics must be performed
             on all patients.

          -  Patients must have complete history and physical exam within 28 days prior to
             registration.

        PATIENT CHARACTERISTICS:

          -  No symptomatic congestive heart failure, coronary artery disease, cardiomyopathy, or
             uncontrolled arrhythmias

               -  Ejection fraction ≥ 45% by echocardiogram or MUGA scan within 28 days prior to
                  registration (or within 14 days prior to registration if the patient has received
                  anthracycline in the 28 day window)

          -  Zubrod performance status 0-2

          -  Serum creatinine ≤ 2.0 times upper limit of normal (ULN)

          -  Total bilirubin ≤ 2.0 times ULN (unless elevation is primarily due to elevated
             unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis AND not
             due to liver dysfunction)

          -  AST and ALT ≤ 3.0 times ULN

          -  Not pregnant or nursing and negative pregnancy test within 14 days prior to
             registration. Females of child-bearing potential must agree to use effective
             contraception

          -  No HIV positivity unless the following criteria are met:

               -  No history of AIDS-defining events

               -  CD4 count ≥ 500/mm³

               -  Viral load < 25,000 copies (< 50 copies if on combination antiretroviral therapy)

               -  Not receiving zidovudine or stavudine as part of combination antiretroviral
                  therapy

          -  No uncontrolled systemic fungal, bacterial, viral, or other infection, defined as
             exhibiting ongoing signs/symptoms related to the infection with no improvement despite
             appropriate antibiotics or other treatment

          -  Patients with prior malignancy (other than AML and MDS/CMML) eligible provided patient
             is in remission from that malignancy at least 6 months prior to registration. Except
             for AML and MDS treatment, all treatment related toxicities must have been resolved.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete remission (CR) rate (including CR with incomplete recovery)
Time Frame:5 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Southwest Oncology Group

Trial Keywords

  • recurrent adult acute myeloid leukemia
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)

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