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

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ClinicalTrials.gov Identifier: NCT01831232
Recruitment Status : Completed
First Posted : April 15, 2013
Results First Posted : November 17, 2017
Last Update Posted : November 17, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mazyar Shadman, Fred Hutchinson Cancer Research Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions 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
Interventions Drug: pravastatin sodium
Drug: idarubicin
Drug: cytarabine
Other: laboratory biomarker analysis
Enrollment 24
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
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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
Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
Hide 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 Number of Baseline Participants 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 24 participants
57
(35 to 72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
15
  62.5%
Male
9
  37.5%
Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Acute Myeloid Leukemia (AML)
21
  87.5%
Myelodysplastic Syndrome (MDS)
2
   8.3%
Chronic Myelomonocytic Leukemia (CMML)
1
   4.2%
1.Primary Outcome
Title Number of Participants With Good Complete Remission (CR)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
Hide 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 Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
12
  50.0%
2.Primary Outcome
Title Number of Participants With TRM.
Hide Description

A Bayesian design intended to simultaneously monitor efficacy and toxicity will be used.

TRM: Treatment Related Mortality

Time Frame 28 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
Hide 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 Number of Participants Analyzed 24
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participants
2
(1 to 27)
3.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description [Not Specified]
Time Frame 1 year after treatment with IAP
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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 Number of Participants Analyzed 17
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients with PFS
52.6
(28.7 to 71.9)
4.Secondary Outcome
Title Overall Survival
Hide Description Amount of time a patient lives after treatment with IAP
Time Frame 1 year after treatment with IAP
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
Hide 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 Number of Participants Analyzed 24
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients surviving
53.5
(32 to 71)
5.Secondary Outcome
Title Number of Biomarker-positive Participants With Clinical Responses
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants with biomarkers: FLT3-ITD positive, NPM1 positive or CEBPA
Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
Hide 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 Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: participants with clinical responses
0
6.Secondary Outcome
Title Rate of Complete Remission (CR), Remission With Incomplete Blood Count Recovery (CRi) and Partial Remission (PR)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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 Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
CR
15
  62.5%
CRi
2
   8.3%
PR
0
   0.0%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
Hide 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 (%)
Total   6/24 (25.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
Affected / at Risk (%) # Events
Total   2/24 (8.33%)    
General disorders   
Multi organ failure secondary to sepsis *  2/24 (8.33%)  2
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)
Affected / at Risk (%) # Events
Total   24/24 (100.00%)    
Blood and lymphatic system disorders   
Febrile neutropenia Grade 3 *  17/24 (70.83%)  17
Febrile neutropenia Grade 4 *  1/24 (4.17%)  1
Gastrointestinal disorders   
Diarrhea Grade 3 *  6/24 (25.00%)  6
Nausea/Vomiting *  4/24 (16.67%)  4
Mucositis *  3/24 (12.50%)  3
Colon pneumatosis Grade 3 *  1/24 (4.17%)  1
GI bleeding Grade 3 *  1/24 (4.17%)  1
Infections and infestations   
Septic shock (Grade 4) *  1/24 (4.17%)  1
Investigations   
Transaminitis Grade 3 *  2/24 (8.33%)  2
Metabolism and nutrition disorders   
Tumor lysis syndrome Grade 3 *  1/24 (4.17%)  1
Skin and subcutaneous tissue disorders   
Rash Grade 3 *  3/24 (12.50%)  3
Hand-foot syndrome Grade 3 *  2/24 (8.33%)  2
*
Indicates events were collected by non-systematic assessment
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
Responsible Party: Mazyar Shadman, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01831232     History of Changes
Other Study ID Numbers: 2674.00
NCI-2013-00743 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2674.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Submitted: April 8, 2013
First Posted: April 15, 2013
Results First Submitted: April 14, 2017
Results First Posted: November 17, 2017
Last Update Posted: November 17, 2017