NCT01130506

Decitabine, Vorinostat, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Phase I Study of Decitabine, Vorinostat, and Cytarabine in Acute Myeloid Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years – 59 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and the best dose of cytarabine when given together with decitabine and vorinostat in treating patients with acute myeloid leukemia or myelodysplastic syndrome that has returned or has not responded to treatment. Drugs used in chemotherapy, such as cytarabine and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cytarabine together with decitabine and vorinostat may kill more cancer cells.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of the combination of decitabine, vorinostat, and cytarabine in patients with relapsed/refractory acute myeloid leukemia (AML) and select subsets of high risk leukemia/myelodysplastic syndromes (MDS). II. To define the specific toxicities and the dose limiting toxicity (DLT) of the combination. SECONDARY OBJECTIVES: I. To develop a platform for specifically targeting mixed-lineage leukemia partial-tandem duplication (MLL PTD), for future efficacy studies. II. To determine the overall response rate (ORR) of this regimen in relapsed/ refractory AML. III. To examine the role of decitabine and vorinostat in re-expression of mixed-lineage leukemia wild type (MLL- WT) in patients with MLL PTD via correlative studies specific to patients with MLL PTD and the preliminary relationship of this to clinical response in patients with MLL PTD+ AML. IV. To correlate the biological activity of decitabine as demethylating agent (changes in target gene methylation and gene expression, deoxyribonucleic acid \[DNA\] \[cytosine-5-\]-methyltransferase 1 \[DNMT1\] protein expression, global methylation) with clinical endpoints. V. To explore the biologic role of microribonucleic acids (RNAs) in determining clinical response to the combination and achievement of the other pharmacodynamic endpoints. OUTLINE: This is a dose-escalation study of cytarabine. INDUCTION THERAPY: Patients receive decitabine intravenously (IV) over 1 hour on days 1-10; vorinostat orally (PO) on days 5-10; and high-dose cytarabine IV over 2 hours on days 12, 14, and 16 in the absence of disease progression or unacceptable toxicity. Patients who achieve complete remission (CR) proceed to maintenance therapy. Patients who achieve CR with incomplete blood count recovery undergo bone marrow aspiration and biopsy at count recovery or day 42 before proceeding to maintenance therapy. MAINTENANCE THERAPY: Patients receive decitabine IV over 1 hour on days 1-5 and vorinostat PO on days 5-10. Treatment repeats every 28 days for up to 11 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.

Conditions

• Previously Treated Myelodysplastic Syndrome
• Recurrent Adult Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia
• Secondary Acute Myeloid Leukemia
• Therapy-Related Acute Myeloid Leukemia
• Untreated Adult Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Cytarabine	Given IV
DRUG	Decitabine	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
DRUG	Vorinostat	Given PO

Timeline

• Start date: 2010-05-17
• Primary completion: 2012-11-19
• First posted: 2010-05-26
• Last updated: 2017-08-02

Locations

2 sites across 1 country: United States