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

NCT ID: NCT02390414

Last Updated: 2023-04-03

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 290 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2020-09-30

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).

Conditions

Myelodysplastic Syndromes (MDS)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Gets HSCT

Patients with higher-risk myelodysplastic syndrome (MDS) aged 60-75 who are fit for HSCT and actually undergo HSCT.

No interventions assigned to this group

No HSCT

Patients with higher-risk myelodysplastic syndrome (MDS) aged 60-75 who are fit for HSCT but do not undergo HSCT.

No interventions assigned to this group

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.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Gregory A. Abel, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gregory A Abel, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://doi.org/10.1038/s41375-020-01092-2

Fit older adults with advanced myelodysplastic syndromes: who is most likely to benefit from transplant?

Other Identifiers

11-056

Identifier Type: -

Identifier Source: org_study_id