Status:

COMPLETED

Decitabine Maintenance for Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS) Post Transplant

Lead Sponsor:

Washington University School of Medicine

Conditions:

Leukemia, Myeloid, Acute

Myelodysplastic Syndromes

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

Primary: To determine the maximum tolerated dose and schedule of decitabine when administered as maintenance therapy after allogeneic hematopoietic stem cell transplantation (alloHSCT) performed for ...

Detailed Description

Secondary: * To determine the safety and tolerability of decitabine as maintenance therapy after alloHSCT. * To determine the rates disease relapse, 1-year disease-free survival, and overall survival...

Eligibility Criteria

Inclusion

  • Patient Screening Criteria and Enrollment Process
  • This is a single institution study at Washington University School of Medicine in St. Louis. Study population are patients \>=18 years of age, with histologically confirmed AML or MDS according to World Health Organization (WHO) criteria undergoing alloHCST. All screening procedures are part the patients clinical care.
  • Patients, or their legal authorized representative, will provide written informed consent for the study prior to alloHSCT, or through 100 days following alloHSCT
  • Patients will undergo alloHSCT as per institutional guidelines. AlloHSCT may be performed using both related and unrelated donors, myeloablative or non-myeloablative preparative regimens, and with either peripheral blood or bone marrow as a source of graft.
  • Patients who fulfill both the Inclusion Criteria and Exclusion Criteria in the period of ≥ 50 and ≤ 100 days after alloHSCT will be registered on the study and will receive decitabine maintenance. Bone marrow biopsy will be performed ≤ 14 days prior to starting decitabine to confirm remission. Any GVHD prophylaxis or therapy is allowed during the study.
  • Patients who do not fulfill Inclusion Criteria are not eligible to be registered on the study and are considered screening failures.
  • Study will include maximum of 32 evaluable patients.
  • Inclusion Criteria
  • History of AML or MDS using WHO classification.
  • \>50 and \<100 days following HLA-matched related or unrelated donor alloHSCT. 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 years.
  • Bone marrow biopsy confirming complete remission after alloHSCT
  • o Complete remission: less than 5% blasts in an aspirate bone marrow sample with a count of at least 200 nucleated cells, no blasts with Auer rods or persistence of extramedullary disease PLUS absolute neutrophil count (ANC) \> 1,500/μL, platelet count ≥ 50,000/μL and no leukemic blasts in the peripheral blood.
  • Platelet count ≥ 50,000/µL without platelet transfusion for 7 days and ANC ≥ 1,500/µL without colony stimulating factor support.
  • Performance status \< ECOG 2.
  • Acceptable organ function defined as:
  • 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.
  • Each Patient or their legal authorized representative must sign an institutional review board/ethics committee-approved informed consent indicating their awareness of the investigational nature of this study.
  • Female Subjects:
  • Female of childbearing potential (FCBP\*) must agree to use a reliable form of contraception or to practice complete abstinence from heterosexual intercourse for at least 28 days before starting study drug, while participating in the study, and for at least 28 days after discontinuation from the study. The methods of reliable contraception include intrauterine device (IUD), hormonal (birth control pills, injections, or implants), tubal ligation, partner's vasectomy, latex condom, diaphragm and cervical cap.
  • FCBP must agree to pregnancy testing.
  • FCBP must a negative pregnancy test prior to starting study drug.
  • FCBP must agree to abstain from donating blood and/or egg during study participation and for at least 28 days after discontinuation from the study
  • \* A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months).
  • Male Subjects:
  • Must agree to use a latex condom during sexual contact with FCBP while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy
  • Must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from the study.
  • Must agree that if a pregnancy or a positive pregnancy test does occur in a female partner of a male study subject during study participation, study drug must be immediately discontinued and must immediately notify the principal investigator.
  • Exclusion Criteria
  • History of previous alloHSCT prior to the current alloHSCT.
  • Persistent AML or MDS after alloHSCT.
  • Grade 3- 4 acute GVHD, See Appendix A.
  • 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.

Exclusion

    Key Trial Info

    Start Date :

    December 1 2009

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    February 1 2016

    Estimated Enrollment :

    24 Patients enrolled

    Trial Details

    Trial ID

    NCT00986804

    Start Date

    December 1 2009

    End Date

    February 1 2016

    Last Update

    February 15 2016

    Active Locations (1)

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    Washington University School of Medicine

    St Louis, Missouri, United States, 63110