AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia
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.
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
Drug: HDAC inhibitor AR-42
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of AR-42 and Decitabine in Acute Myeloid Leukemia|
- BETD (biologic effective and tolerable dose) of HDAC inhibitor AR-42, defined as a doubling in miR-29b levels from baseline [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
- Maximum tolerated dose (MTD) based on incidence of dose-limiting toxicity (DLT) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
- Incidence of adverse events, graded according to the NCI CTCAE v4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]Toxicities will be tabulated by dose level and summarized in addition to assessing the incidence of DLTs. Severe (grade 3+) toxicities will be summarized by type as well as in summary format of hematologic vs. non-hematologic severe toxicity incidence. DLT-level toxicities will also be summarized and tracked beyond the first cycle of therapy.
|Study Start Date:||September 2013|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (HDAC inhibitor AR-42, decitabine)
INDUCTION THERAPY: Patients receive HDAC inhibitor AR-42 PO daily on days 1, 3, and 5 or 1, 3, 4, 5 and decitabine 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 CR or 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.
Drug: HDAC inhibitor AR-42
Other Name: AR-42Drug: decitabine
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01798901
|Contact: Ohio State University Comprehensive Cancer Center||1-800-293-5066||Jamesline@osumc.edu|
|Contact: Alison Walker, MDemail@example.com|
|United States, Ohio|
|Cincinnati Children's Hospital||Recruiting|
|Cincinnati, Ohio, United States, 45229|
|Contact: Laura Fossett 513-636-2799 firstname.lastname@example.org|
|Contact: Lori Backus 513-636-2799 email@example.com|
|Principal Investigator: Christine Phillips, MD|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Alison R. Walker, MD 614-366-3802 Alison.firstname.lastname@example.org|
|Principal Investigator: Alison R. Walker, MD|
|Sub-Investigator: Guido Marcucci, MD|
|Sub-Investigator: William Blum, MD|
|Sub-Investigator: John Byrd, MD|
|Sub-Investigator: Rebecca Klisovic, MD|
|Sub-Investigator: Steven Devine, MD|
|Sub-Investigator: Jeffrey Jones, MD, MPH|
|Sub-Investigator: Don Benson, MD, PhD|
|Sub-Investigator: Sumi Vasu, MBBS|
|Sub-Investigator: Katherine Walsh, MD|
|Sub-Investigator: Ramiro Garzon, MD|
|Sub-Investigator: Joseph Flynn, DO, MPH|
|Sub-Investigator: Thomas Gross, MD, PhD|
|Sub-Investigator: John Perentesis, MD|
|Sub-Investigator: Christine Phillips, MD|
|Sub-Investigator: Robyn Dennis, MD|
|Nationwide Children's Hospital||Suspended|
|Columbus, Ohio, United States, 43205|
|Principal Investigator:||Alison Walker, MD||Ohio State University Comprehensive Cancer Center|