NCT02264873

Phase I, Dose Escalation Study of Decitabine

Minimizing Leukemia Relapse: A Phase I, Dose Escalation Study of Decitabine in High Risk Pediatric Leukemia Post Allogeneic Transplant

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 1 Year – 30 Years
• Healthy volunteers: Not accepted

Summary

Decitabine is a hypomethylating agent that has shown significant anti-leukemic effect in Myelodysplastic Syndrome (MDS) and Acute Myeloblastic Leukemia (AML). This study is based on the hypothesis that Decitabine delivered after allo-hematopoietic stem cell transplant (HSCT) in patients with leukemia will enhance disease control by the allogeneic immune system and lead to a longer disease free survival. The study is designed to provide safety data of low-dosing in the post-transplant setting.

Detailed description

Decitabine is a hypomethylating agent with significant anti-leukemic effect in MDS and AML. Additionally, aberrant DNA methylation has been identified in high risk childhood ALL, and therefore, DNA hypomethylating agents, such as decitabine, have been identified as therapeutic agents. Moreover, decitabine has immunomodulatory effects by enhancement of class I human leukocyte antigen (HLA) antigen expression on cancer cells, which increases their susceptibility to immune surveillance mechanisms, such as graft-versus-leukemia effect of donor cells in allogeneic transplantation and by augmentation of natural killer (NK), T and B lymphocyte reactivity. We hypothesize that decitabine delivered after allo-HSCT in patients with leukemia will enhance disease control by the allogeneic immune system and lead to a longer disease free survival. However, a safety study is needed to determine appropriate decitabine dosing in the post-transplant period. Low doses of decitabine are likely better tolerated in the post-transplant setting given risks of myelosuppression. In addition, when administered at lower doses, decitabine's hypomethylation effects are more pronounced in relation to its pyrimidine analog cytotoxic effects. In this study low doses of decitabine will be administered beginning 6 weeks to 100 days post-transplant. Measures of gene methylation and immune reconstitution will be conducted to define biologically active doses. Results from this trial will provide new clinical data regarding the effects of decitabine on gene methylation and immunoreactivity, will establish a maximally tolerated dose in the post-transplant setting, will define biologically active doses, and will serve as a basis for future efficacy trials.

Conditions

• Leukemia, Lymphoblastic, Acute
• Leukemia, Myeloid Acute
• Hematopoetic Myelodysplasia

Interventions

Type	Name	Description
DRUG	Decitabine	Dose escalation starting at 5 mg, and increasing by 2.5 mg to a Dose Level of 12.5 mg qd x 3 days.

Timeline

• Start date: 2014-10-01
• Primary completion: 2016-10-01
• Completion: 2018-09-18
• First posted: 2014-10-15
• Last updated: 2018-10-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study