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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01812252
First received: March 14, 2013
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

This clinical trial studies different chemotherapies in treating patients with myelodysplastic syndrome before donor stem cell transplant. Giving chemotherapy before a donor hematopoietic stem cell transplant helps stop the growth of cancer cells before, 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 Intervention
Chronic Myelomonocytic Leukemia
de Novo Myelodysplastic Syndromes
Secondary Myelodysplastic Syndromes
Drug: decitabine
Drug: azacitidine
Drug: cytarabine
Drug: idarubicin
Drug: daunorubicin hydrochloride
Procedure: quality-of-life assessment

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Initial Cytoreductive Therapy for Myelodysplastic Syndrome Prior to Allogeneic Hematopoietic Cell Transplantation (the ICT-HCT Study)

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Failure-free survival (failure defined as death, lack of response to initial therapy, relapse after response to initial therapy) [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Frequency at which the patients undergo transplantation [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Factors present at enrollment that predict transplant frequency [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Reasons for which patients were not transplanted [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Changes in quality of life scores using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) [ Time Frame: Baseline and up to 18 months ] [ Designated as safety issue: No ]
  • Change in comorbidities [ Time Frame: Baseline and time of transplant ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Relapse [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Relapse-free survival [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Incidence of acute and chronic GVHD assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 18 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: April 2013
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (decitabine or azacitidine)
Patients receive decitabine or azacitidine IV or SC for 7 days. Treatment repeats every 28 days for 4 courses of decitabine or 6 courses of azacitidine in the absence of disease progression or unacceptable toxicity.
Drug: decitabine
Given IV or SC
Other Names:
  • 5-aza-dCyd
  • 5AZA
  • DAC
Drug: azacitidine
Given IV or SC
Other Names:
  • 5-AC
  • 5-azacytidine
  • azacytidine
  • Vidaza
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm B (cytarabine, idarubicin or daunorubicin hydrochloride)
Patients receive cytarabine IV continuously over 24 hours for 7 days and idarubicin IV or daunorubicin hydrochloride IV on days 1-3 at the discretion of the treating physician. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: idarubicin
Given IV
Other Names:
  • 4-demethoxydaunorubicin
  • 4-DMDR
  • DMDR
  • IDA
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. Determine if IC (intensive AML-like therapy) in comparison to HMA as initial therapy, will affect transplantation frequency, quality of life, pre-hematopoietic cell transplantation (HCT) toxicity, and transplant candidacy.

II. Conduct exploratory analysis of post-HCT outcomes (overall survival, non relapse mortality, incidence of graft rejection, graft-versus-host disease [GVHD], relapse, and relapse-free survival).

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 courses of decitabine or 6 courses of azacitidine in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive cytarabine IV continuously over 24 hours for 7 days and idarubicin IV or daunorubicin hydrochloride IV on days 1-3 at the discretion of the treating physician. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 18 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • Patients in which adequate marrow/biopsy specimens cannot be obtained to determine disease burden by morphologic assessment, but have fulfilled criteria (abnormal myeloblast count >= 5% and < 20%) by flow cytometry are still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures
  • 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; the attending may use metrics such as Treatment Related Mortality Score (TRM) or Karnofsky performance status, in addition to clinical values (age, platelet count, serum albumin, secondary or de novo disease, white blood cell count, peripheral blood blast percentage, and serum creatinine) to determine if a patient should be included
  • Considered a potential transplant candidate; the attending physician will determine transplant candidacy at the time of initial visit
  • Human leukocyte antigen (HLA)-typing must be requested by the time of enrollment, but does not need to be resulted to enroll
  • Males should be willing to use an effective contraceptive method during the study and for a minimum of 6 months after study treatment
  • Women must be postmenopausal or must be willing to use an acceptable method of contraception to avoid pregnancy for the entire period of the study and for at least 3 months after the study; a postmenopausal woman is defined as a woman who has experienced amenorrhea > 12 consecutive months or a woman on hormone replacement therapy with documented follicle-stimulating hormone (FSH) level > 35 mIU/mL; for patients in whom menopausal state is in question, a negative pregnancy test will be required prior to enrollment
  • 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; previous treatment with iron chelation, growth factors (filgrastim [GCSF], erythropoiesis stimulating agent, or thrombopoietin mimetics), small molecule inhibitors, or immune modulatory drugs (thalidomide, lenalidomide) is acceptable
  • Use of any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea
  • 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)
  • Pregnant or lactating patients
  • 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 leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01812252

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Bart L. Scott    800-422-6237      
Principal Investigator: Bart L. Scott         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Bart Scott Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01812252     History of Changes
Other Study ID Numbers: 2661.00, NCI-2013-00538, P30CA015704
Study First Received: March 14, 2013
Last Updated: April 2, 2014
Health Authority: United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:
myelodysplastic syndrome
chronic myelomonocytic leukemia
bone marrow transplant
hypomethylating agent
induction chemotherapy

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Leukemia
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Azacitidine
Cytarabine
Decitabine
Daunorubicin
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on August 26, 2014