Trial record 1 of 1 for:    NCT00986804
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Decitabine Maintenance for Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS) Post Transplant (AML MDS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00986804
First received: September 29, 2009
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

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 AML or high-risk MDS.


Condition Intervention Phase
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Drug: Decitabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Maintenance Therapy With Decitabine After Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • To determine the maximum tolerated dose and schedule of decitabine when administered as maintenance therapy after alloHSCT performed for AML or high-risk MDS. [ Time Frame: 6 weeks (1st cycle) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the safety and tolerability of decitabine as maintenance therapy after alloHSCT. [ Time Frame: 30 days after end of study ] [ Designated as safety issue: Yes ]
  • To determine the rates disease relapse [ Time Frame: Every 3 months for 2 years then every 6 months for 3 years ] [ Designated as safety issue: No ]
  • To assess lymphoid and myeloid chimerism while on decitabine maintenance. [ Time Frame: End of cycle 3 ] [ Designated as safety issue: No ]
  • To determine the incidence of acute GVHD. [ Time Frame: End of study ] [ Designated as safety issue: Yes ]
  • To assess immunologic reconstitution after alloHSCT. [ Time Frame: End of study ] [ Designated as safety issue: Yes ]
  • To assess changes in gene expression and methylation patterns following decitabine treatment [ Time Frame: End of study ] [ Designated as safety issue: Yes ]
    No more than 8 cycles

  • To assess the effects of decitabine on immune reconstitution post transplant. [ Time Frame: End of study ] [ Designated as safety issue: Yes ]
  • To access the frequency of FoxP3+ CD3+/CD4+ and CD3+/CD8+ lymphocytes before and after decitabine treatment. [ Time Frame: End of cycle 3 ] [ Designated as safety issue: Yes ]
  • To determine the 1-year disease-free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To determine overall survival. [ Time Frame: Every 3 months for 2 years then every 6 months for 3 years ] [ Designated as safety issue: No ]
  • To determine the incidence of chronic GVHD. [ Time Frame: End of study ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: December 2009
Estimated Study Completion Date: November 2017
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Level 1
Decitabine 5.0 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles.
Drug: Decitabine
Other Name: Dacogen
Experimental: Level 2
Decitabine 7.5 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles.
Drug: Decitabine
Other Name: Dacogen
Experimental: Level 3
Decitabine 10.0 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles.
Drug: Decitabine
Other Name: Dacogen
Experimental: Level 4
Decitabine 15.0 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles.
Drug: Decitabine
Other Name: Dacogen

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.
  • To assess lymphoid and myeloid chimerism while on decitabine maintenance.
  • To determine the incidence of acute and chronic GVHD.
  • To assess immunologic reconstitution after alloHSCT.
  • To assess changes in gene expression and methylation patterns following decitabine treatment
  • To assess the effects of decitabine on immune reconstitution post transplant.
  • To access the frequency of FoxP3+ CD3+/CD4+ and CD3+/CD8+ lymphocytes before and after decitabine treatment.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00986804

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Iskra Pusic, M.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:
Blum W, Bruner-Klisovic R, Liu S, et al. Phase I Study of Low Dose Decitabine in Patients with Acute Myeloid Leukemia (AML): Pharmacokinetics (PK), Pharmacodynamics (PD), and Clinical Activity. ASH Annual Meeting Abstracts. 2005;106:1861-.
Choi J, Ritchey J, DiPersio J. Generation of Treg-Like Cells from CD4+CD25- T Cells Via Epigenetic Modification Using a Demethylating Agent Decitabine. ASH Annual Meeting Abstracts. 2007;110:62-.
De Lima M, de Padua Silva L, Giralt S, et al. Maintenance Therapy with Low-Dose Azacitidine (AZA) after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Relapsed or Refractory AML or MDS: A Dose and Schedule Finding Study. ASH Annual Meeting Abstracts. 2008;112:1134-.

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00986804     History of Changes
Other Study ID Numbers: 09-1126 / 201108378
Study First Received: September 29, 2009
Last Updated: August 11, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Decitabine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014