The Myelodysplasia Transplantation-Associated Outcomes (MDS-TAO) Study

• ClinicalTrials.gov Identifier: NCT02390414
• Recruitment Status: Completed
• First Posted: March 17, 2015
• Results First Posted: April 3, 2023
• Last Update Posted: April 3, 2023
• Sponsor: Dana-Farber Cancer Institute
• Information provided by (Responsible Party): Gregory A. Abel, MD, Dana-Farber Cancer Institute

Tracking Information

• First Submitted Date: March 11, 2015
• First Posted Date: March 17, 2015
• Results First Submitted Date: March 3, 2022
• Results First Posted Date: April 3, 2023
• Last Update Posted Date: April 3, 2023
• Actual Study Start Date: May 2011
• Actual Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 30, 2023)

Overall Survival [ Time Frame: 3 Years ]

To prospectively compare the overall survival of patients in the HSCT group to that of patients in the non-HSCT group.

Original Primary Outcome Measures (submitted: March 11, 2015)

Overall Survival [ Time Frame: 5 Years ]

To prospectively compare the overall survival of patients in the HSCT group to that of patients in the non-HSCT group.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Myelodysplasia Transplantation-Associated Outcomes (MDS-TAO) Study
• Official Title: The Myelodysplasia Transplantation-Associated Outcomes (MDS-TAO) Study
• Brief Summary: The purpose of this observational study is to compare overall survival in older adults with myelodysplastic syndromes (MDS) who receive reduced intensity conditioning hematopoietic stem cell transplant (RIC HSCT) versus those who do not receive HSCT.

Detailed Description

MDS is a hematologic malignancy characterized by cytopenias, bone marrow failure, and a risk of transformation to acute myeloid leukemia (AML). HSCT is the only curative therapy for MDS. Despite its increasing use among older patients (age greater than 60), more data are needed to assess outcomes of HSCT in older adults compared to other therapies.

In this observational study, patients with MDS presenting at the study institutions are screened for disease characteristics that indicate that they are potentially appropriate for HSCT (both high-risk disease and fit for the procedure). Patients who meet inclusion and exclusion criteria and agree to participate in the study are entered into a clinical database and followed for overall survival. Patients also complete quality of life (QoL) assessments at enrollment and two years afterward, with the goal of investigating potential relationships between QoL and MDS treatment (HSCT vs. non-HSCT strategies).

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Eligible patients will be 60 to 75 years old with a diagnosis of MDS or related disorder (eg, MDS/MPD or CMML) who have disease that is advanced enough to warrant RIC HSCT (defined by high-risk cytogenetics OR int-2 or high-risk on IPSS OR transfusion dependence as defined by WPSS) and who are physically fit enough to undergo RIC HSCT as assessed by pre-determined measures of organ function. Patients whose baseline donor status is known will be excluded; however, knowledge of HLA status is allowed as long as a donor search has not been performed.
• Condition: Myelodysplastic Syndromes (MDS)
• Intervention: Not Provided

Study Groups/Cohorts

• Gets HSCT
  Patients with higher-risk myelodysplastic syndrome (MDS) aged 60-75 who are fit for HSCT and actually undergo HSCT.
• No HSCT
  Patients with higher-risk myelodysplastic syndrome (MDS) aged 60-75 who are fit for HSCT but do not undergo HSCT.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 11, 2015): 290
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: September 2020
• Actual Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically-confirmed diagnosis of:

  • Primary or secondary MDS using the World Health Organization (WHO) 2008 classification:

    • Refractory cytopenia with unilineage dysplasia

      • Refractory Anemia (RA)
      • Refractory Neutropenia (RN)
      • Refractory Thrombocytopenia (RT)
    • Refractory Anemia with Ring Sideroblasts (RARS)
    • Refractory Cytopenia with Multilineage Dysplasia (RCMD)
    • Refractory Anemia with Excess Blasts-1 (RAEB-1)
    • Refractory Anemia with Excess Blasts-2 (RAEB-2)
    • MDS with isolated del (5q)
    • MDS-Unclassified (MDS-U)

  • Another of the following related disorders:

    • Chronic Myelomonocytic leukemia (CMML)
    • Myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPD-U)
• Age 60 to 75 years

• Any of the following (high-risk characteristics):

  • Intermediate-2 or High-Risk on International Prognostic Scoring System (IPSS)
  • Secondary MDS (any karyotype)

  • Documented non-IPSS intermediate- or poor-prognosis karyotype including:

    • +8
    • t(11q23)
    • Rea 3q
    • +19
    • 3 or greater abnormalities
    • del(7q)
    • -5
    • t(5q)

  • Documented significant cytopenia for at least four months prior to enrollment, defined by the following criteria:

    • Red Blood Cell (RBC) Transfusion Dependence: four or more units of RBC transfusions within an eight-week period for symptomatic anemia with hemoglobin of ≤ 9.0 g/dL; OR
    • Severe Anemia: average of two or more hemoglobin values ≤ 8 g/dL within an eight-week period not influenced by RBC transfusions (i.e., must be seven days post transfusion); OR

    • Severe Thrombocytopenia: average of two or more platelet counts ≤ 50

      × 109/L within an eight-week period not influenced by platelet transfusions (i.e., must be at least three days post- transfusion) or a clinically significant hemorrhage requiring platelet transfusions within the prior four months; OR

    • Severe Neutropenia: average of two or more absolute neutrophil counts (ANC) ≤ 500 within an eight-week period, or a clinically significant infection requiring IV antibiotics in the setting of ANC ≤ 1000 within the prior four months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

• Adequate organ function to permit RIC HSCT as indicated by the following:

  • Serum bilirubin ≤ 2.5 mg/dL (except when Gilbert's syndrome or MDS-related hemolysis suspected).
  • Aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN).
  • Serum creatinine ≤ 2.0 mg/dL.
  • Seemingly sufficient baseline cardiac function to undergo HSCT (no echocardiogram required).
  • Seemingly sufficient baseline pulmonary function to undergo HSCT (no pulmonary function tests required).
  • Seemingly sufficient neuro-psychiatric function to undergo HSCT (no specific neuro-psychiatric evaluation required).
• Willingness to undergo human leukocyte antigen (HLA)-typing and consider subsequent HSCT.
• Willingness and ability to give informed consent.

Exclusion Criteria:

• Known baseline conversion to AML (eg, ≥ 20% peripheral or marrow blasts).
• Knowledge of potential donor status at study entry. Of note, knowledge of HLA status WITHOUT a related or unrelated search is allowed.
• History of prior malignancy within the past year, except for adequately-treated carcinoma in situ of uterine cervix, basal cell or squamous cell skin cancer.
• Any severe concurrent disease, infection, or comorbidity that, in the judgment of the principal investigator, would make the patient inappropriate for HSCT at the time of study entry.
• Psychiatric disorders including dementia that would preclude obtaining informed consent or the ability to participate in an ongoing research study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02390414
• Other Study ID Numbers: 11-056
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Gregory A. Abel, MD, Dana-Farber Cancer Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Dana-Farber Cancer Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Gregory A Abel, MD, MPH; Dana-Farber Cancer Institute

• PRS Account: Dana-Farber Cancer Institute
• Verification Date: March 2023