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| ID | Type | Description | Link |
|---|---|---|---|
| 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 | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (pravastatin sodium, idarubicin, and cytarabine) | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| pravastatin sodium | Drug | Given PO |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 35 days |
| Number of Participants With TRM. | A Bayesian design intended to simultaneously monitor efficacy and toxicity will be used. TRM: Treatment Related Mortality | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) | 1 year after treatment with IAP | |
| Overall Survival | Amount of time a patient lives after treatment with IAP | 1 year after treatment with IAP |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mazyar Shadman | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. pravastatin sodium: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| idarubicin | Drug | Given IV |
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| cytarabine | Drug | Given IV |
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| laboratory biomarker analysis | Other | Correlative studies |
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| 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). | 38 days after dosing |
| 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) | 35 days |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. pravastatin sodium: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Diagnosis | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 35 days |
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| Primary | Number of Participants With TRM. | A Bayesian design intended to simultaneously monitor efficacy and toxicity will be used. TRM: Treatment Related Mortality | Posted | Number | 95% Confidence Interval | participants | 28 days |
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| Secondary | Progression Free Survival (PFS) | 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. | Posted | Number | 95% Confidence Interval | percentage of patients with PFS | 1 year after treatment with IAP |
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| Secondary | Overall Survival | Amount of time a patient lives after treatment with IAP | Posted | Number | 95% Confidence Interval | percentage of patients surviving | 1 year after treatment with IAP |
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| Secondary | 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). | Participants with biomarkers: FLT3-ITD positive, NPM1 positive or CEBPA | Posted | Number | participants with clinical responses | 38 days after dosing |
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| Secondary | 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) | 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. | Posted | Count of Participants | Participants | 35 days |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. pravastatin sodium: Given PO idarubicin: Given IV cytarabine: Given IV laboratory biomarker analysis: Correlative studies | 6 | 24 | 2 | 24 | 24 | 24 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Multi organ failure secondary to sepsis | General disorders | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia Grade 3 | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Febrile neutropenia Grade 4 | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Rash Grade 3 | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Hand-foot syndrome Grade 3 | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Septic shock (Grade 4) | Infections and infestations | Non-systematic Assessment |
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| Diarrhea Grade 3 | Gastrointestinal disorders | Non-systematic Assessment |
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| Nausea/Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
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| Mucositis | Gastrointestinal disorders | Non-systematic Assessment |
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| Transaminitis Grade 3 | Investigations | Non-systematic Assessment |
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| Colon pneumatosis Grade 3 | Gastrointestinal disorders | Non-systematic Assessment |
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| GI bleeding Grade 3 | Gastrointestinal disorders | Non-systematic Assessment |
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| Tumor lysis syndrome Grade 3 | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr, Mazyar Shadman | Fred Hutchinson Cancer Research Ctr | 206-667-5467 | mshadman@fredhutch.org |
| ID | Term |
|---|---|
| D007947 | Leukemia, Megakaryoblastic, Acute |
| D007948 | Leukemia, Monocytic, Acute |
| D015470 | Leukemia, Myeloid, Acute |
| D000013 | Congenital Abnormalities |
| D015479 | Leukemia, Myelomonocytic, Acute |
| D004915 | Leukemia, Erythroblastic, Acute |
| D015477 | Leukemia, Myelomonocytic, Chronic |
| D009196 | Myeloproliferative Disorders |
| D000754 | Anemia, Refractory, with Excess of Blasts |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D001855 | Bone Marrow Diseases |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000753 | Anemia, Refractory |
| D000740 | Anemia |
| D009190 | Myelodysplastic Syndromes |
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| ID | Term |
|---|---|
| D017035 | Pravastatin |
| D015255 | Idarubicin |
| D003561 | Cytarabine |
| ID | Term |
|---|---|
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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| Chronic Myelomonocytic Leukemia (CMML) |
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