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Phase I, Dose Escalation Study of Decitabine

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. Identifier: NCT02264873
Recruitment Status : Completed
First Posted : October 15, 2014
Last Update Posted : October 15, 2018
Hyundai Hope On Wheels
Information provided by (Responsible Party):
University of Florida

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.

Condition or disease Intervention/treatment Phase
Leukemia, Lymphoblastic, Acute Leukemia, Myeloid Acute Hematopoetic Myelodysplasia Drug: Decitabine Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Minimizing Leukemia Relapse: A Phase I, Dose Escalation Study of Decitabine in High Risk Pediatric Leukemia Post Allogeneic Transplant
Study Start Date : October 2014
Actual Primary Completion Date : October 2016
Actual Study Completion Date : September 18, 2018

Arm Intervention/treatment
This is a 3+3 design of dose escalation
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.
Other Name: Decitabine, Dacogen

Primary Outcome Measures :
  1. Maximum Tolerated Dose as a Measure of Safety and Tolerability [ Time Frame: 3 months ]
    This is a dose escalation study of decitabine maintenance therapy after allo-HSCT for the maximally tolerated dose in pediatric patients without adverse events.

Secondary Outcome Measures :
  1. Adverse Event Profile After Single Cycle Decitabine Post Transplant [ Time Frame: 6 months ]
    The adverse events will be graded using the NCI Scale after one cycle of decitabine maintenance therapy intravenously. Grade 1 and 2 are unexpected and expect but unlikely related or unrelated; Grade 3 unexpected with hospitalization within 10 calendar days or possibly, probable related and without hospitalization; Grade 3 expected with hospitalization within 10 days or without hospitalization; Grade 4 and 5 Unexpected and Expected 24-hours to 5 days unlikely, unrelated, possible, probable, definite.

  2. Grade 3 Adverse Events after Decitabine [ Time Frame: 6 months ]
    To estimate the incidences of ≥ grade 3 adverse events, infections, need for transfusions, treatment related mortality (TRM), and incidence and severity of graft vs host disease (GVHD) after initiation of decitabine post-HSCT. The grading will be done with the NCI Scale Grade 3 unexpected with hospitalization within 10 calendar days or possibly, probable related and without hospitalization; Grade 3 expected with hospitalization within 10 days or without hospitalization.

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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;

Information from the National Library of Medicine

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 identifier (NCT number): NCT02264873

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United States, Florida
UF Health Shands Hospital
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
Hyundai Hope On Wheels
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Principal Investigator: Paul Castillo, MD University of Florida
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Responsible Party: University of Florida Identifier: NCT02264873    
Other Study ID Numbers: IRB201400612
PEDS004 ( Other Identifier: University of Florida Protocol ID )
First Posted: October 15, 2014    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Florida:
Autologous stem cell transplant
Additional relevant MeSH terms:
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Leukemia, Myeloid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors