S0919 Idarubicin, Cytarabine, and Pravastatin in Treating Patients With Relapsed Acute Myeloid Leukemia - Full Text View

Purpose

RATIONALE: 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 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Pravastatin may also help idarubicin and cytarabine work better by making cancer cells more sensitive to the drugs. Giving idarubicin and cytarabine together with pravastatin may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving idarubicin and cytarabine together with pravastatin works in treating patients with relapsed acute myeloid leukemia.

Condition	Intervention	Phase
Leukemia	Drug: cytarabine Drug: idarubicin Drug: pravastatin sodium	Phase 2

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	S0919, A Phase II Study of Idarubicin and Ara-C in Combination With Pravastatin for Relapsed Acute Myelogenous Leukemia (AML)

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia

Drug Information available for: Cytarabine Idarubicin hydrochloride Idarubicin Pravastatin Pravastatin sodium

U.S. FDA Resources

Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:

Complete remission (CR) rate (including CR with incomplete recovery) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Relapse-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Toxicity as assessed by NCI CTCAE version 4.0 [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Correlation between pre-study cytogenetic features and response [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	August 2009
Estimated Study Completion Date:	November 2015
Estimated Primary Completion Date:	March 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: treatment Induction (1 cycle): pravastatin 1280 mg/d PO D 1-8 idarubicin 12 mg/m2/d IV D 4-6 AraC 1.5 g/m2/d contIV D 4-7 Consolidation (up to 2 cycles): pravastatin 1280 mg/d PO D 1-6 idarubicin 12 mg/m2/d IV D 4-5 AraC 1.5 g/m2/d contIV D 4-5	Drug: cytarabine Drug: idarubicin Drug: pravastatin sodium

Detailed Description:

OBJECTIVES:

To test whether the complete remission (CR) rate (including CR with incomplete recovery) in patients with relapsed acute myeloid leukemia treated with idarubicin and cytarabine in combination with pravastatin is sufficiently high to warrant a phase III investigation.
To estimate relapse-free survival and overall survival rates in these patients.
To estimate the frequency and severity of toxicities of this regimen in these patients.
To evaluate, in a preliminary manner, whether pre-study cytogenetic features correlate with response in these patients.

OUTLINE: This is a multicenter study.

Induction therapy: Patients receive oral pravastatin once daily on days 1-8, idarubicin IV over 10-15 minutes on days 4-6, and cytarabine IV continuously on days 4-7. Patients achieving complete remission proceed to consolidation therapy.
Consolidation therapy: Beginning 30-60 days after the start of induction therapy, patients receive oral pravastatin once daily on days 1-6 and idarubicin IV over 10-15 minutes and cytarabine IV continuously on days 4 and 5. Treatment repeats approximately every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Morphologically confirmed diagnosis of acute myeloid leukemia (AML)
Must have received ≥ 1 prior chemotherapy regimen for AML
- Any type of prior chemotherapy allowed
- Must have achieved a complete remission (CR) (including CR with incomplete recovery) that lasted ≥ 3 months after the last induction regimen and then subsequently relapsed
  - Relapse must be documented by a bone marrow examination demonstrating > 5% blasts in the bone marrow not attributable to another cause
No acute promyelocytic leukemia (i.e., APL, FAB M3) or blastic transformation of chronic myelogenous leukemia
No clinical evidence of leptomeningeal disease
Concurrent registration on research study SWOG-9007 required

PATIENT CHARACTERISTICS:

Zubrod performance status 0-2
Serum creatinine ≤ 2.0 times upper limit of normal (ULN)
Total bilirubin ≤ 2.0 times ULN (unless elevation is primarily due to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis AND not due to liver dysfunction)
AST and ALT ≤ 3.0 times ULN
Ejection fraction ≥ 45% by echocardiogram or MUGA scan
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No symptomatic congestive heart failure, coronary artery disease, cardiomyopathy, or uncontrolled arrhythmias
No HIV positivity unless the following criteria are met:
- No history of AIDS-defining events
- CD4 count ≥ 500/mm³
- Viral load < 25,000 copies (< 50 copies if on combination antiretroviral therapy)
- Not receiving zidovudine or stavudine as part of combination antiretroviral therapy
No uncontrolled systemic fungal, bacterial, viral, or other infection, defined as exhibiting ongoing signs/symptoms related to the infection with no improvement despite appropriate antibiotics or other treatment
Other prior malignancy allowed provided patient is in remission from that malignancy

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 6 months since prior chemotherapy or radiotherapy and recovered
No prior autologous or allogeneic stem cell transplantation
Prior or concurrent hydroxyurea to control high WBC counts allowed
No concurrent statin treatments

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00840177

Show 85 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Anjali Advani, MD

The Cleveland Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Southwest Oncology Group
ClinicalTrials.gov Identifier:	NCT00840177 History of Changes
Other Study ID Numbers:	CDR0000633749, S0919, U10CA032102
Study First Received:	February 7, 2009
Last Updated:	January 2, 2013
Health Authority:	United States: Federal Government

Keywords provided by Southwest Oncology Group:

recurrent adult acute myeloid leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)

adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Pravastatin
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents

Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Anticholesteremic Agents
Hypolipidemic Agents
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on June 13, 2013