AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01798901|
Recruitment Status : Active, not recruiting
First Posted : February 26, 2013
Last Update Posted : January 20, 2017
|Condition or disease||Intervention/treatment||Phase|
|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 Drug: decitabine Other: laboratory biomarker analysis Other: pharmacological study||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||54 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of AR-42 and Decitabine in Acute Myeloid Leukemia|
|Actual Study Start Date :||September 17, 2013|
|Primary Completion Date :||August 24, 2016|
|Estimated Study Completion Date :||December 31, 2017|
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
- 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 ]
- 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 ]
- Incidence of adverse events, graded according to the NCI CTCAE v4.0 [ Time Frame: Up to 3 years ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01798901
|United States, Ohio|
|Cincinnati Children's Hospital|
|Cincinnati, Ohio, United States, 45229|
|Nationwide Children's Hospital|
|Columbus, Ohio, United States, 43205|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Alison Walker, MD||Ohio State University Comprehensive Cancer Center|