Decitabine Augments for Post Allogeneic Stem Cell Transplantation in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndrome

Allo - hematopoietic stem cell transplantation is currently the only way to cure myelodysplastic syndrome /acute leukemia . The existing experimental results showed that decitabine and 5-azacytidine up-regulated the expression of tumor Ags on leukemic blasts in vitro and expanded the numbers of immunomodulatory T regulatory cells in animal models. Reasoning that decitabine might selectively augment a graft versus leukemia effect, the investigators used decitabine administration after allogeneic stem cell transplantation to studied the immunologic sequelae.

Study Overview

• Status: Unknown
• Conditions: Myelodysplastic Syndromes; Acute Myelocytic Leukemia
• Intervention / Treatment: Drug: decitabine

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • First Affiliated Hospital, SooChow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed AML in complete or partial remission or MDS using WHO classification undergoing alloHSCT
• High resolution typing HLA-matched related or unrelated donor. Donors may be mismatched at single antigen at HLA-A, -B or -DR locus plus possible single antigen mismatch at HLA-C according to institution guidelines. Two-antigen mismatch at a single locus is not allowed.
• Age ≥ 18
• creatinine < 1.5 times the institutional ULN or creatinine clearance (calculated by the Cockroft and Gault method) ≥ 30 mL/min
• bilirubin < 1.5 times the institutional ULN
• AST, ALT and alkaline phosphatase < 2.5 times the institutional ULN.

Exclusion Criteria:

• History of previous alloHSCT prior to the current alloHSCT.
• Persistent AML or MDS after alloHSCT.
• Positive serology for HIV.
• Pregnancy or nursing.
• Other cancers less than or equal to 2 years prior study entry except: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, prostate cancer stage T1a or T1b.
• Uncontrolled active infections requiring intravenous antibiotics. Clinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), which, in the judgment of the Principal or Associate Investigator would compromise the patient's ability to tolerate protocol therapy.
• Known or suspected hypersensitivity to decitabine.
• Patients may not be receiving any other investigational agents.
• General or specific changes in patient's condition that render the patient unacceptable for further treatment in judgment of the investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: decitabine; 36 mg/m2 on day 42 after transplantation and administered daily for 5 consecutive days every 28 days for up to a total of 10 cycles	Drug: decitabine; 36 mg/m2 on day 42 after transplantation and administered daily for 5 consecutive days every 28 days for up to a total of 10 cycles
No Intervention: no decitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the effects of decitabine on graft versus leukemia post transplant.	three years

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess immunologic reconstitution after allo HSCT	three years

Other Outcome Measures

Outcome Measure	Time Frame
To assess lymphoid and myeloid chimerism post transplantation	three years
To determine the incidence of acute and chronic GVHD	three years
To determine the rates disease relapse, 3-year disease-free survival, and overall survival	three years
To access the frequency of FoxP3+ CD4+CD25+ lymphocytes and WT1 specific CTL before and after decitabine treatment	three years
To assess changes in WT1 gene expression and methylation patterns before and after following decitabine treatment	three years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: Xian-Janssen Pharmaceutical Ltd.
• Investigators: Study Director: Fu chengcheng, Phd, First Affiliated Hospital, SooChow University

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): December 1, 2013
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: January 18, 2013
• First Submitted That Met QC Criteria: March 10, 2013
• First Posted (Estimate): March 12, 2013

Study Record Updates

• Last Update Posted (Estimate): March 12, 2013
• Last Update Submitted That Met QC Criteria: March 10, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Decitabine; Regulatory T cell; hematopoietic stem cell transplant; Wilms' tumor 1; cytolytic T lymphocyte
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: hematology-02