Phase I, Dose Escalation Study of Decitabine

NCT ID: NCT02264873

Last Updated: 2018-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2018-09-18

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Decitabine

This is a 3+3 design of dose escalation

Group Type: OTHER

Decitabine

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Decitabine, Dacogen

Eligibility Criteria

Inclusion Criteria

• Age: greater than 1 and less than 31 years of age;
• Diagnosis: history of ALL, AML or MDS, currently in a complete remission (CR) following allo-HSCT (bone marrow leukemic blasts less than 5% by morphology), with high risk features including:
• Status post allogeneic HSCT
• GVHD prophylaxis:
• Karnofsky or Lansky performance scores more than 50%. Karnofsky scores will be used for patients > 16 years of age and Lansky scores for patients ≤ 16 years of age;
• Platelet count ≥ 50,000 (untransfused);
• Absolute neutrophil count ≥ 1000; and;
• Hemoglobin ≥ 8 g/dL (un-transfused);

Exclusion Criteria

• Progressive disease;
• Philadelphia chromosome positive ALL (these patients receive tyrosine kinase inhibitor posttransplant);
• Known hypersensitivity to any components of decitabine;
• Uncontrolled grade 3-4 graft versus host disease;
• Uncontrolled infection;
• Serum creatinine > 2 mg/dL or glomerular filtration rate (GFR) less than 60 mL/min/1.73m2 ;
• Alanine Aminotransferase (ALT) greater than 3 times normal or serum total bilirubin greater than 2 mg/dL;

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hyundai Hope On Wheels

OTHER

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Castillo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

UF Health Shands Hospital

Gainesville, Florida, United States

Countries

United States

Other Identifiers

PEDS004

Identifier Type: OTHER

Identifier Source: secondary_id

IRB201400612

Identifier Type: -

Identifier Source: org_study_id