Trial Outcomes & Findings for Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes (NCT NCT01831232)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

24 participants

Primary outcome timeframe

35 days

Results posted on

2017-11-17

Participant Flow

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	24
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) n=24 Participants 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
Age, Continuous	57 years n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Diagnosis Acute Myeloid Leukemia (AML)	21 Participants n=5 Participants
Diagnosis Myelodysplastic Syndrome (MDS)	2 Participants n=5 Participants
Diagnosis Chronic Myelomonocytic Leukemia (CMML)	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) n=24 Participants 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
Number of Participants With Good Complete Remission (CR)	12 Participants

PRIMARY outcome

Timeframe: 28 days

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

Outcome measures

Outcome measures
Measure	Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) n=24 Participants 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
Number of Participants With TRM.	2 participants Interval 1.0 to 27.0

SECONDARY outcome

Timeframe: 1 year after treatment with IAP

Population: 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.

Outcome measures

Outcome measures
Measure	Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) n=17 Participants 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
Progression Free Survival (PFS)	52.6 percentage of patients with PFS Interval 28.7 to 71.9

SECONDARY outcome

Timeframe: 1 year after treatment with IAP

Amount of time a patient lives after treatment with IAP

Outcome measures

Outcome measures
Measure	Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) n=24 Participants 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 Survival	53.5 percentage of patients surviving Interval 32.0 to 71.0

SECONDARY outcome

Timeframe: 38 days after dosing

Population: Participants with biomarkers: FLT3-ITD positive, NPM1 positive or CEBPA

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).

Outcome measures

Outcome measures
Measure	Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) n=6 Participants 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
Number of Biomarker-positive Participants With Clinical Responses	0 participants with clinical responses

SECONDARY outcome

Timeframe: 35 days

Population: 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.

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)

Outcome measures

Outcome measures
Measure	Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) n=24 Participants 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
Rate of Complete Remission (CR), Remission With Incomplete Blood Count Recovery (CRi) and Partial Remission (PR) PR	0 Participants
Rate of Complete Remission (CR), Remission With Incomplete Blood Count Recovery (CRi) and Partial Remission (PR) CR	15 Participants
Rate of Complete Remission (CR), Remission With Incomplete Blood Count Recovery (CRi) and Partial Remission (PR) CRi	2 Participants

Adverse Events

Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine)

Serious events: 2 serious events

Other events: 24 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) n=24 participants at risk 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
General disorders Multi organ failure secondary to sepsis	8.3% 2/24 • Number of events 2

Other adverse events

Other adverse events
Measure	Treatment (Pravastatin Sodium, Idarubicin, and Cytarabine) n=24 participants at risk 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
Blood and lymphatic system disorders Febrile neutropenia Grade 3	70.8% 17/24 • Number of events 17
Blood and lymphatic system disorders Febrile neutropenia Grade 4	4.2% 1/24 • Number of events 1
Skin and subcutaneous tissue disorders Rash Grade 3	12.5% 3/24 • Number of events 3
Skin and subcutaneous tissue disorders Hand-foot syndrome Grade 3	8.3% 2/24 • Number of events 2
Infections and infestations Septic shock (Grade 4)	4.2% 1/24 • Number of events 1
Gastrointestinal disorders Diarrhea Grade 3	25.0% 6/24 • Number of events 6
Gastrointestinal disorders Nausea/Vomiting	16.7% 4/24 • Number of events 4
Gastrointestinal disorders Mucositis	12.5% 3/24 • Number of events 3
Investigations Transaminitis Grade 3	8.3% 2/24 • Number of events 2
Gastrointestinal disorders Colon pneumatosis Grade 3	4.2% 1/24 • Number of events 1
Gastrointestinal disorders GI bleeding Grade 3	4.2% 1/24 • Number of events 1
Metabolism and nutrition disorders Tumor lysis syndrome Grade 3	4.2% 1/24 • Number of events 1

Additional Information

Dr, Mazyar Shadman

Fred Hutchinson Cancer Research Ctr

Phone: 206-667-5467

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place