Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT01831232
Collaborator
National Cancer Institute (NCI) (NIH)
24
1
1
32
0.7

Study Details

Study Description

Brief Summary

This clinical trial studies idarubicin, cytarabine, and pravastatin sodium in treating patients with newly diagnosed acute myeloid leukemia or myelodysplastic syndromes. 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 sodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving idarubicin and cytarabine together with pravastatin sodium may kill more cancer cells.

Detailed Description

PRIMARY OBJECTIVES:
  1. To assess the rate of achieving a "good complete response (CR)" after treating patients with newly diagnosed acute myeloid leukemia (AML) with idarubicin, cytarabine and pravastatin (pravastatin sodium) (IAP).

  2. To determine the toxicity (death within 28 days of starting therapy = treatment related mortality or "TRM") with IAP in newly-diagnosed AML.

SECONDARY OBJECTIVES:
  1. To determine rates of complete remission (CR), remission with incomplete blood count recovery (CRi), partial remission (PR), relapse-free survival and overall survival.

  2. To identify biomarkers (ie. changes in serum cholesterol) associated with clinical responses.

OUTLINE:

Patients receive pravastatin sodium orally (PO) once daily (QD) on days 1-8, idarubicin intravenously (IV) over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then annually for 3 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Idarubicin, Cytarabine and Pravastatin (IAP) for Induction of Newly Diagnosed Acute Myeloid Leukemia (AML)
Study Start Date :
May 1, 2013
Actual Primary Completion Date :
Feb 1, 2015
Actual Study Completion Date :
Jan 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (pravastatin sodium, idarubicin, and cytarabine)

Patients receive pravastatin sodium PO QD on days 1-8, idarubicin IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Drug: pravastatin sodium
Given PO
Other Names:
  • PRAV
  • Pravachol
  • Drug: idarubicin
    Given IV
    Other Names:
  • 4-demethoxydaunorubicin
  • 4-DMDR
  • DMDR
  • IDA
  • Drug: cytarabine
    Given IV
    Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
  • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Good Complete Remission (CR) [35 days]

      A Bayesian design intended to simultaneously monitor efficacy and toxicity will be used. Definition of Good CR: Conventional criteria for CR (absolute neutrophil count > 1,000/uL, platelet count > 100,000/uL, marrow with <5% morphologic blasts) and additionally the requirements that marrow Minimal Residual Disease (MRD) - detected by 10-color flow cytometry or conventional cytogenetic evaluation - be absent and that the above blood counts be obtained.

    2. Number of Participants With TRM. [28 days]

      A Bayesian design intended to simultaneously monitor efficacy and toxicity will be used. TRM: Treatment Related Mortality

    Secondary Outcome Measures

    1. Progression Free Survival (PFS) [1 year after treatment with IAP]

    2. Overall Survival [1 year after treatment with IAP]

      Amount of time a patient lives after treatment with IAP

    3. Number of Biomarker-positive Participants With Clinical Responses [38 days after dosing]

      Biomarkers: FLT3-ITD positive, NPM1 positive, CEBPA. A "good CR" is defined as <5% blasts in the marrow by morphologic evaluation along with the absence of any MRD by flow cytometry or cytogenetics and recovery of blood counts (platelets >100,00 and absolute neutrophil count >1,000) by day 35 after induction. Cheson AML Response Criteria is used for Morphologic Leukemia Free State, Morphologic Complete Remission, Cytogenetic Complete Remission (CRc), Molecular Complete Remission (CRm), Morphologic Complete Remission with Incomplete Blood Count Recovery (CRi), Partial Remission (PR), Treatment Failure, Recurrence (Progressive Disease).

    4. Rate of Complete Remission (CR), Remission With Incomplete Blood Count Recovery (CRi) and Partial Remission (PR) [35 days]

      Complete remission (CR) - includes patients with good CR and CR with minimal residual disease (MRD); remission with incomplete blood count recovery (CRi), partial remission (PR)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 74 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically or cytologically confirmed diagnosis of acute myeloid leukemia by World Health Organization (WHO) 2008 criteria, including patients with >= 20% blasts in the bone marrow or peripheral blood (except acute promyelocytic leukemia), or myelodysplastic syndrome refractory anemia with excess blasts (RAEB)-2 by WHO classification or advanced myeloproliferative neoplasm with >= 10% blasts in the bone marrow or peripheral blood, including chronic myelomonocytic leukemia (CMML) CMML-2 by WHO 2008 classification

    • Untreated AML or high-risk myelodysplastic syndrome (MDS) and a simplified TRM score of =< 9.2

    • Bilirubin < 2.0 mg/ml

    • Any creatinine value is acceptable

    • Any performance status is eligible

    • Life expectancy otherwise > 1 year

    • Patients are not excluded based on cardiac history

    • Females of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment

    • Patients must use an effective contraceptive method during the study and for a minimum of 90 days after study treatment

    • Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle Washington United States 98109

    Sponsors and Collaborators

    • Fred Hutchinson Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Mazyar Shadman, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mazyar Shadman, Principal Investigator, Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01831232
    Other Study ID Numbers:
    • 2674.00
    • NCI-2013-00743
    • 2674.00
    • P30CA015704
    First Posted:
    Apr 15, 2013
    Last Update Posted:
    Nov 17, 2017
    Last Verified:
    Oct 1, 2017

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
    Arm/Group Description Patients receive pravastatin sodium PO QD on days 1-8, idarubicin IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. pravastatin sodium: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies
    Period Title: Overall Study
    STARTED 24
    COMPLETED 24
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
    Arm/Group Description Patients receive pravastatin sodium PO QD on days 1-8, idarubicin IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. pravastatin sodium: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies
    Overall Participants 24
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    57
    Sex: Female, Male (Count of Participants)
    Female
    15
    62.5%
    Male
    9
    37.5%
    Diagnosis (Count of Participants)
    Acute Myeloid Leukemia (AML)
    21
    87.5%
    Myelodysplastic Syndrome (MDS)
    2
    8.3%
    Chronic Myelomonocytic Leukemia (CMML)
    1
    4.2%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Good Complete Remission (CR)
    Description A Bayesian design intended to simultaneously monitor efficacy and toxicity will be used. Definition of Good CR: Conventional criteria for CR (absolute neutrophil count > 1,000/uL, platelet count > 100,000/uL, marrow with <5% morphologic blasts) and additionally the requirements that marrow Minimal Residual Disease (MRD) - detected by 10-color flow cytometry or conventional cytogenetic evaluation - be absent and that the above blood counts be obtained.
    Time Frame 35 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
    Arm/Group Description Patients receive pravastatin sodium PO QD on days 1-8, idarubicin IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. pravastatin sodium: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies
    Measure Participants 24
    Count of Participants [Participants]
    12
    50%
    2. Primary Outcome
    Title Number of Participants With TRM.
    Description A Bayesian design intended to simultaneously monitor efficacy and toxicity will be used. TRM: Treatment Related Mortality
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
    Arm/Group Description Patients receive pravastatin sodium PO QD on days 1-8, idarubicin IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. pravastatin sodium: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies
    Measure Participants 24
    Number (95% Confidence Interval) [participants]
    2
    8.3%
    3. Secondary Outcome
    Title Progression Free Survival (PFS)
    Description
    Time Frame 1 year after treatment with IAP

    Outcome Measure Data

    Analysis Population Description
    Patients who had a good complete remission (CR), CR with evidence of minimal residual disease (MRD), or complete remission with incomplete blood count recovery (CRi) following treatment. Cheson AML Response Criteria are used to assess response.Good CR is defined as <5% blasts in marrow, no MRD and recovery of blood counts by day 35 after induction.
    Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
    Arm/Group Description Patients receive pravastatin sodium PO QD on days 1-8, idarubicin IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. pravastatin sodium: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies
    Measure Participants 17
    Number (95% Confidence Interval) [percentage of patients with PFS]
    52.6
    4. Secondary Outcome
    Title Overall Survival
    Description Amount of time a patient lives after treatment with IAP
    Time Frame 1 year after treatment with IAP

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
    Arm/Group Description Patients receive pravastatin sodium PO QD on days 1-8, idarubicin IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. pravastatin sodium: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies
    Measure Participants 24
    Number (95% Confidence Interval) [percentage of patients surviving]
    53.5
    5. Secondary Outcome
    Title Number of Biomarker-positive Participants With Clinical Responses
    Description Biomarkers: FLT3-ITD positive, NPM1 positive, CEBPA. A "good CR" is defined as <5% blasts in the marrow by morphologic evaluation along with the absence of any MRD by flow cytometry or cytogenetics and recovery of blood counts (platelets >100,00 and absolute neutrophil count >1,000) by day 35 after induction. Cheson AML Response Criteria is used for Morphologic Leukemia Free State, Morphologic Complete Remission, Cytogenetic Complete Remission (CRc), Molecular Complete Remission (CRm), Morphologic Complete Remission with Incomplete Blood Count Recovery (CRi), Partial Remission (PR), Treatment Failure, Recurrence (Progressive Disease).
    Time Frame 38 days after dosing

    Outcome Measure Data

    Analysis Population Description
    Participants with biomarkers: FLT3-ITD positive, NPM1 positive or CEBPA
    Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
    Arm/Group Description Patients receive pravastatin sodium PO QD on days 1-8, idarubicin IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. pravastatin sodium: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies
    Measure Participants 6
    Number [participants with clinical responses]
    0
    0%
    6. Secondary Outcome
    Title Rate of Complete Remission (CR), Remission With Incomplete Blood Count Recovery (CRi) and Partial Remission (PR)
    Description Complete remission (CR) - includes patients with good CR and CR with minimal residual disease (MRD); remission with incomplete blood count recovery (CRi), partial remission (PR)
    Time Frame 35 days

    Outcome Measure Data

    Analysis Population Description
    All patient who received IAP treatment were assessed for response. The number of participants with CR, CRi and PR are included in the table below.
    Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
    Arm/Group Description Patients receive pravastatin sodium PO QD on days 1-8, idarubicin IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. pravastatin sodium: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies
    Measure Participants 24
    CR
    15
    62.5%
    CRi
    2
    8.3%
    PR
    0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
    Arm/Group Description Patients receive pravastatin sodium PO QD on days 1-8, idarubicin IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Treatment repeats every 28-56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. pravastatin sodium: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies
    All Cause Mortality
    Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
    Affected / at Risk (%) # Events
    Total 6/24 (25%)
    Serious Adverse Events
    Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
    Affected / at Risk (%) # Events
    Total 2/24 (8.3%)
    General disorders
    Multi organ failure secondary to sepsis 2/24 (8.3%) 2
    Other (Not Including Serious) Adverse Events
    Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
    Affected / at Risk (%) # Events
    Total 24/24 (100%)
    Blood and lymphatic system disorders
    Febrile neutropenia Grade 3 17/24 (70.8%) 17
    Febrile neutropenia Grade 4 1/24 (4.2%) 1
    Gastrointestinal disorders
    Diarrhea Grade 3 6/24 (25%) 6
    Nausea/Vomiting 4/24 (16.7%) 4
    Mucositis 3/24 (12.5%) 3
    Colon pneumatosis Grade 3 1/24 (4.2%) 1
    GI bleeding Grade 3 1/24 (4.2%) 1
    Infections and infestations
    Septic shock (Grade 4) 1/24 (4.2%) 1
    Investigations
    Transaminitis Grade 3 2/24 (8.3%) 2
    Metabolism and nutrition disorders
    Tumor lysis syndrome Grade 3 1/24 (4.2%) 1
    Skin and subcutaneous tissue disorders
    Rash Grade 3 3/24 (12.5%) 3
    Hand-foot syndrome Grade 3 2/24 (8.3%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr, Mazyar Shadman
    Organization Fred Hutchinson Cancer Research Ctr
    Phone 206-667-5467
    Email mshadman@fredhutch.org
    Responsible Party:
    Mazyar Shadman, Principal Investigator, Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01831232
    Other Study ID Numbers:
    • 2674.00
    • NCI-2013-00743
    • 2674.00
    • P30CA015704
    First Posted:
    Apr 15, 2013
    Last Update Posted:
    Nov 17, 2017
    Last Verified:
    Oct 1, 2017