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

Primary Purpose

Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a)

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
pravastatin sodium
idarubicin
cytarabine
laboratory biomarker analysis
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Acute Megakaryoblastic Leukemia (M7)

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (pravastatin sodium, idarubicin, and cytarabine)

Arm 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.

Outcomes

Primary Outcome Measures

Number of Participants With Good Complete Remission (CR)
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.
Number of Participants With TRM.
A Bayesian design intended to simultaneously monitor efficacy and toxicity will be used. TRM: Treatment Related Mortality

Secondary Outcome Measures

Progression Free Survival (PFS)
Overall Survival
Amount of time a patient lives after treatment with IAP
Number of Biomarker-positive Participants With Clinical Responses
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).
Rate of Complete Remission (CR), Remission With Incomplete Blood Count Recovery (CRi) and Partial Remission (PR)
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)

Full Information

First Posted
April 8, 2013
Last Updated
October 16, 2017
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01831232
Brief Title
Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
Official Title
Idarubicin, Cytarabine and Pravastatin (IAP) for Induction of Newly Diagnosed Acute Myeloid Leukemia (AML)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. 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: I. 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). II. To determine the toxicity (death within 28 days of starting therapy = treatment related mortality or "TRM") with IAP in newly-diagnosed AML. SECONDARY OBJECTIVES: I. To determine rates of complete remission (CR), remission with incomplete blood count recovery (CRi), partial remission (PR), relapse-free survival and overall survival. II. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), 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), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Refractory Anemia With Excess Blasts, Untreated Adult Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (pravastatin sodium, idarubicin, and cytarabine)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
pravastatin sodium
Other Intervention Name(s)
PRAV, Pravachol
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
idarubicin
Other Intervention Name(s)
4-demethoxydaunorubicin, 4-DMDR, DMDR, IDA
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cytarabine
Other Intervention Name(s)
ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
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
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
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Time Frame
1 year after treatment with IAP
Title
Overall Survival
Description
Amount of time a patient lives after treatment with IAP
Time Frame
1 year after treatment with IAP
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mazyar Shadman
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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