ICT-HCT: Chemotherapy in Treating Patients With Myelodysplastic Syndrome Before Donor Stem Cell Transplant

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01812252

Collaborator

(none)

Enrollment

Locations

Arms

126

Anticipated Duration (Months)

11.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myelomonocytic Leukemia de Novo Myelodysplastic Syndrome Myelodysplastic Syndrome Secondary Myelodysplastic Syndrome	Drug: Azacitidine Drug: Decitabine Other: Quality-of-Life Assessment	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

To determine the effect of induction chemotherapy (IC) (intensive acute myeloid leukemia [AML]-like therapy), versus less intensive hypomethylating agents (HMA) as initial therapy, on failure-free survival.

SECONDARY OBJECTIVES:

Determine if IC (intensive AML-like therapy) in comparison to HMA as initial therapy, will affect transplantation frequency and quality of life.
Conduct exploratory analysis of post-HCT outcomes (overall survival, and relapse).

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 2, 2013

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Other: Arm A (decitabine or azacitidine) 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 Given IV or SC Other Names: 5 AZC 5-AC 5-Azacytidine 5-AZC Azacytidine Azacytidine, 5- Ladakamycin Mylosar U-18496 Vidaza Drug: Decitabine Given IV or SC Other Names: 5-Aza-2'-deoxycytidine Dacogen Decitabine for Injection Deoxyazacytidine Dezocitidine Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment
Other: Arm B (induction-like chemotherapy regimen) 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 Ancillary studies Other Names: Quality of Life Assessment

Arm

Intervention/Treatment

Other: Arm A (decitabine or azacitidine)

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

Given IV or SC

Other Names:

5 AZC

5-AC

5-Azacytidine

5-AZC

Azacytidine

Azacytidine, 5-

Ladakamycin

Mylosar

U-18496

Vidaza

Drug: Decitabine

Given IV or SC

Other Names:

5-Aza-2'-deoxycytidine

Dacogen

Decitabine for Injection

Deoxyazacytidine

Dezocitidine

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Other: Arm B (induction-like chemotherapy regimen)

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

Ancillary studies

Other Names:

Quality of Life Assessment

Outcome Measures

Primary Outcome Measures

Failure-free survival (failure defined as death or relapse) [18 months]

Secondary Outcome Measures

Changes in quality of life scores using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [Baseline, pre-transplant, and up to 100 days post-transplant]
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.
Frequency at which the patients undergo transplantation [Up to 18 months]
Overall Survival [Up to 18 months]
Relapse [Up to 18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
2	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
3	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
4	Kaiser Permanente Washington	Seattle	Washington	United States	98112