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

NCT ID: NCT00986804

Last Updated: 2016-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2016-02-29

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 AML or high-risk MDS.

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.

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Level 1

Decitabine 5.0 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles.

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

Level 2

Decitabine 7.5 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles.

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

Level 3

Decitabine 10.0 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles.

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

Level 4

Decitabine 15.0 mg/m2/day on Days 1 thru 5 every 6 weeks for as many as 8 cycles.

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

Interventions

Decitabine

Intervention Type: DRUG

Other Intervention Names

Dacogen

Eligibility Criteria

Inclusion Criteria

• Study will include maximum of 32 evaluable patients.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Iskra Pusic, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

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-.

Reference Type: BACKGROUND

Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, Klimek V, Slack J, de Castro C, Ravandi F, Helmer R 3rd, Shen L, Nimer SD, Leavitt R, Raza A, Saba H. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006 Apr 15;106(8):1794-803. doi: 10.1002/cncr.21792.

Reference Type: BACKGROUND

PMID: 16532500 (View on PubMed)

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-.

Reference Type: BACKGROUND

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-.

Reference Type: BACKGROUND

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

09-1126 / 201108378

Identifier Type: -

Identifier Source: org_study_id