NCT01798901

AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia

Phase I Study of AR-42 and Decitabine in Acute Myeloid Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Alison Walker · Academic / Other
• Sex: All
• Age: 3 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of AR-42 when given together with decitabine in treating patients with acute myeloid leukemia. AR-42 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving AR-42 together with decitabine may kill more cancer cells.

Detailed description

PRIMARY OBJECTIVES: I. To determine the biologic effective and tolerable dose (BETD) of AR-42 (histone deacetylase \[HDAC\] inhibitor AR-42) in combination with a 10 day schedule of decitabine in acute myeloid leukemia (AML) in adults (Stratum 1) and children (Stratum 2). II. To define the specific toxicities and the dose limiting toxicity (DLT) of AR-42 in combination with a 10 day schedule of decitabine in adults and children. SECONDARY OBJECTIVES: I. To describe biologic activity of the combination of AR-42 and decitabine (changes in micro ribonucleic acid \[RNA\] \[miR\]-29b expression; specificity protein 1 \[Sp1\], deoxyribonucleic acid \[DNA\] (cytosine-5-)-methyltransferase \[DNMT\]1, 3A and 3B, KIT and FMS-like tyrosine kinase 3 \[FLT3\] RNA and protein levels). II. To provide preliminary data for clinical response with the combination of AR-42 and decitabine in adults and in children. III. To provide preliminary data on correlation of biologic endpoints and clinical response (particularly miR-29b expression). OUTLINE: This is a dose-escalation study of HDAC inhibitor AR-42. INDUCTION THERAPY: Patients receive HDAC inhibitor AR-42 orally (PO) daily on days 1, 3, and 5 or 1, 3, 4, 5 and decitabine intravenously (IV) over 1 hour on days 6-15. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete remission (CR) or morphologic CR with incomplete blood count recovery (CRi) receive HDAC inhibitor AR-42 as in Induction Therapy and decitabine IV over 1 hour on days 6-10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Conditions

• Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
• Adult Acute Myeloid Leukemia With Del(5q)
• 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)
• Recurrent Adult Acute Myeloid Leukemia
• Recurrent Childhood Acute Myeloid Leukemia
• Secondary Acute Myeloid Leukemia
• Untreated Adult Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	HDAC inhibitor AR-42	Given PO
DRUG	decitabine	Given IV
OTHER	laboratory biomarker analysis	Correlative studies
OTHER	pharmacological study	Correlative studies

Timeline

• Start date: 2013-09-17
• Primary completion: 2015-02-19
• Completion: 2015-02-19
• First posted: 2013-02-26
• Last updated: 2018-03-14

Locations

3 sites across 1 country: United States