Chemotherapy in Treating Patients With Myelodysplastic Syndrome Before Donor Stem Cell Transplant

Study Overview
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Brief Summary
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This randomized clinical trial studies different chemotherapies in treating patients with myelodysplastic syndrome before donor stem cell transplant. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells, and may prevent the myelodysplastic syndrome from coming back after the transplant. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Detailed Description
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OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive decitabine or azacitidine intravenously (IV) or subcutaneously (SC) for 7 days. Treatment repeats every 28 days for 4 cycles of decitabine or 6 cycles of azacitidine in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive induction-like chemotherapy per standard of care or per experimental protocol. This study does not require a specific chemotherapy regimen for Arm B. After completion of study treatment, patients are followed up for 18 months.

Official Title
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Initial Cytoreductive Therapy for Myelodysplastic Syndrome Prior to Allogeneic Hematopoietic Cell Transplantation (the ICT-HCT Study)

Conditions
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Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndrome, Myelodysplastic Syndrome, Secondary Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Azacitidine
* Drug: Decitabine
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of de novo or secondary myelodysplastic syndrome (MDS), including chronic myelomonocytic leukemia, as defined by the 2008 World Health Organization classification system Patients must have measurable disease requiring cytoreduction, defined as a bone marrow myeloblast count >= 5% and < 20% on morphologic examination or by flow cytometry in cases in which adequate morphologic examination is not possible Patients must be considered to have an acceptable risk of early mortality with intensive chemotherapy as determined by the attending physician at the time of the initial visit; since the specific therapy within each arm will be determined after randomization, there is no threshold of organ dysfunction or performance status for inclusion Considered a potential transplant candidate; the attending/treating physician will determine transplant candidacy at the time of consent Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent Exclusion Criteria: A diagnosis of acute promyelocytic leukemia as defined by the 2008 World Health Organization classification system Previous treatment for MDS or AML with intensive chemotherapy regimen (induction chemotherapy) or hypomethylating agent Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) Females who are pregnant or breastfeeding Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment Any uncontrolled or significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results Clinical evidence suggestive of central nervous system (CNS) involvement with MDS unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm B (induction-like chemotherapy regimen)<br>Patients receive physician choice of standard of care or other experimental protocol using induction-like chemotherapy regimen. No one specific regimen is required. Several regimens are listed in the protocol for example only. | Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|
| Other: Arm A (decitabine or azacitidine)<br>Patients receive decitabine or azacitidine IV or SC per standard of care. Treatment repeats per standard of care, every 28 days for 4 cycles of decitabine or 6 cycles of azacitidine in the absence of disease progression or unacceptable toxicity. | Drug: Azacitidine<br>* Given IV or SC<br>* Other names: Vidaza;Drug: Decitabine<br>* Given IV or SC<br>* Other names: Dezocitidine;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival (failure defined as death or relapse) |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in quality of life scores using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 | The quality-of-life questionnaires will be scored. Absolute scores will be reported. A distribution-based interpretation will be conducted using the standardized response mean to analyze changes in scores over time and differences between groups. | Baseline, pre-transplant, and up to 100 days post-transplant | 
| Frequency at which the patients undergo transplantation |  | Up to 18 months | 
| Overall Survival |  | Up to 18 months | 
| Relapse |  | Up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myelodysplastic syndrome, chronic myelomonocytic leukemia, bone marrow transplant, hypomethylating agent, induction chemotherapy