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Maintenance Therapy With Decitabine After Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

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Trial Information

Maintenance Therapy With Decitabine After Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndrome


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.


Inclusion 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 of the patients clinical care.

- Patients who fulfill Pre-transplant Inclusion Criteria (see below) will provide
written informed consent or their legal authorized representative for the study prior
to undergoing alloHSCT. 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 will then have to fulfill both Pre-transplant Inclusion Criteria and
Exclusion Criteria in a period of ≥ 50 and ≤ 100 days after alloHSCT in order be
registered on the study and receive decitabine. 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.

Pre-transplant Inclusion Criteria (to be fulfilled during standard transplant evaluation
within 2 months prior to alloHSCT).

- 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

- 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.

Post-transplant Inclusion Criteria (to be fulfilled after alloHSCT and prior to receiving
decitabine):

- Day +50 and Day +100 after alloHSCT

- Bone marrow biopsy confirming complete remission after alloHSCT

- 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.

- Absence of grade 3-4 acute GVHD.

- 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.

- 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.

- 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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the maximum tolerated dose and schedule of decitabine when administered as maintenance therapy after alloHSCT performed for AML or high-risk MDS.

Outcome Time Frame:

6 weeks (1st cycle)

Safety Issue:

Yes

Principal Investigator

Iskra Pusic, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine

Authority:

United States: Institutional Review Board

Study ID:

09-1126 / 201108378

NCT ID:

NCT00986804

Start Date:

December 2009

Completion Date:

November 2020

Related Keywords:

  • Leukemia, Myeloid, Acute
  • Myelodysplastic Syndromes
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

Washington University School of MedicineSaint Louis, Missouri  63110