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

Phase 2

Completed

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

Interventions: Drug: Azacitidine (AZC)
Drug: Decitabine
Other: Quality-of-Life Assessment

Registration Number: NCT01812252

Lead Sponsor: Fred Hutchinson Cancer Center

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

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 acute myeloblastic leukemia (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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (decitabine or azacitidine)	Azacitidine (AZC)	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.
Arm A (decitabine or azacitidine)	Quality-of-Life Assessment	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.
Arm B (induction-like chemotherapy regimen)	Quality-of-Life Assessment	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.
Arm A (decitabine or azacitidine)	Decitabine	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.

Primary Outcome Measures

Name	Time	Method
Failure-free Survival (Failure Defined as Death or Relapse)	18 months	18-month failure-free survival (failure defined as death or relapse).

Secondary Outcome Measures

Name	Time	Method
Quality of Life Will be Assessed Using the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) Questionnaire.	EORTC QLQ-C30 questionnaire will be collected at screening, after completion of therapy (HMA 4-6 month, and up to 6 months for induction-like chemotherapy) just prior to stem cell infusion and 100 (± 14) days after stem cell infusion (HSCT).	The European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) (version 3) is a 30-item cancer-specific questionnaire for measuring the health-related quality of life (QOL) in cancer patients. It includes five functioning scales (physical, PF; role, RF; cognitive, CF; emotional, EF; and social, SF), three symptom scales (fatigue, FA; pain, PA; and nausea and vomiting, NV), a global health status/QOL scale (GL), and six single items (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial impact of the disease and treatment). All items employ a 4-point Likert scale, ranging from 1 (not at all) to 4 (very much) with lower scores representing a better outcome and higher scores a worse outcome; with the exception of two items in the GL scale, which use 7-point scales (1=very poor to 7=excellent) lower scores representing a worse outcome and higher score representing a better outcome.
Overall Survival	Up to 18 months	The total length of follow-up will be 18 months from the start of treatment (day 1). Four categories were added for participants alive 18 months from start of treatment (day 1) 1) Participants alive after 18 months from start of treatment who received hematopoietic cell transplantation (HCT); 2) Participants alive after 18months from start of treatment who did not receive HCT.; 3) Participants deceased after 18 months from start of treatment who received HCT; 4) Participants deceased after 18 months from start of treatment who did not receive HCT.
Quality of Life Will be Assessed Using the EORTC QLQ-HDC29 a Supplementary Module Assessing the Quality of Life During and After High-dose Chemotherapy and Stem Cell Transplantation.	EORTC QLQ-HDC29 questionnaire will be collected after completion of therapy (HMA 4-6 month, and up to 6 months for induction-like chemotherapy) pre stem cell infusion (HSCT), and 100 (± 14) days post stem cell infusion (HSCT).	European Organization for Research and Treatment of Cancer Quality of Life Questionnaire High Dose Chemotherapy (EORTC QLQ-HDC29) is a treatment-specific quality of life questionnaire that addresses treatment specific side effects as well as emotional, social, and family issues for patients treated with high dose regimens and HCT. The QLQ-HDC29 module includes 29 items, consisting of 6 multi-item scales and 8 single-items; all items employ a 4-point Likert scale, ranging from 1 (not at all) to 4 (very much) with lower scores representing a better outcome and higher scores a worse outcome with the exception of question 47 and 52 being the a higher score resulting in a better outcome and lower score a worse outcome.
Number of Patients Who Relapse Post-transplant	Up to 18 months	To compare which of the two, intensive chemotherapy versus hypomethylating agent-based therapy, have a factor of relapse post hematopoietic cell transplantation (HCT).
Number of Participants Who Received a Hematopoietic Cell Transplantation (HCT).	Up to 18 months	Frequency at which the participants received a hematopoietic cell transplantation (HCT)

Trial Locations

Locations (4): Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Kaiser Permanente Washington
🇺🇸
Seattle, Washington, United States
Fred Hutch/University of Washington Cancer Consortium
🇺🇸
Seattle, Washington, United States
Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States