Clinical trial NCT02390414: The Myelodysplasia Transplantation-Associated Outcomes (MDS-TAO) Study
Official title: The Myelodysplasia Transplantation-Associated Outcomes (MDS-TAO) Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myelodysplastic Syndromes (MDS)
Keywords: Myelodysplastic syndromes (MDS)
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2015-03-17
Enrollment: 290
Sex: ALL
Minimum age (years): 60
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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).

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.

Primary outcomes:
measure: Overall Survival
timeFrame: 3 Years
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Gregory A Abel, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: