Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
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:
-
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).
-
To determine the toxicity (death within 28 days of starting therapy = treatment related mortality or "TRM") with IAP in newly-diagnosed AML.
SECONDARY OBJECTIVES:
-
To determine rates of complete remission (CR), remission with incomplete blood count recovery (CRi), partial remission (PR), relapse-free survival and overall survival.
-
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
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:
Drug: idarubicin
Given IV
Other Names:
Drug: cytarabine
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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
- Progression Free Survival (PFS) [1 year after treatment with IAP]
- Overall Survival [1 year after treatment with IAP]
Amount of time a patient lives after treatment with IAP
- 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).
- 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
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.- 2674.00
- NCI-2013-00743
- 2674.00
- P30CA015704
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
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%
|
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%
|
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
|
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
|
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%
|
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
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 |
mshadman@fredhutch.org |
- 2674.00
- NCI-2013-00743
- 2674.00
- P30CA015704