Myeloproliferative Disorders, Blood Cancer, Myelodysplastic Syndromes
Conditions
Brief summary
To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients with advanced stage MDS and MPD.
Detailed description
Total Lymphoid Irradiation and Anti-Thymocyte Globulin as Conditioning for Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation for the Treatment of Myelodysplastic Syndromes and Myeloproliferative Disorders (except CML). To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients or those with co-morbid conditions that preclude myeloablative transplantation for advanced stage MDS and MPD.
Interventions
PROCEDURETotal Lymphoid Irradiation (TLI)
TLI is administered ten times in 120cGy fractions on day -11 through day -7 and day -4 through day -1
PROCEDUREAnti-Thymocyte Globulin as Conditioning (ATG)
Thymoglobulin will be administered five times intravenously at 1.5 mg/kg/day from day -11 through day -7 for a total dose of 7.5 mg/kg. Thymoglobulin doses will be based on the adjusted ideal body weight if the patient is greater than or equal to 15 kg over ideal body weight.
Sponsors
National Institutes of Health (NIH)
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
49 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
GENERAL INCLUSION CRITERIA * General inclusion criteria must include at least one of the following: * Patients aged \> 49 and \< 75 years with MDS or MPD * Patients aged \< 49 years at high risk for regimen related toxicity using standard high dose regimens. Factors considered high risk include pre-existing conditions such as a chronic disease affecting kidneys, liver, lungs, or heart. * Patients with secondary MDS following a prior autologous transplant. * An HLA-identical related or an HLA-matched unrelated donor is available. ABO incompatibility is acceptable. * A signed informed consent form. MYELODYSPLASTIC SYNDROME CRITERIA * Diagnosis of MDS classifiable by the FAB system as refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), chronic myelomonocytic leukemia (CMML), refractory anemia with excess blasts (RAEB), and MDS transformed to acute leukemia. * Patients with advanced MDS must be cytoreduced to \< 10% marrow blasts prior to receiving conditioning with TLI/ATG. Less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning. The cytoreductive regimen will be determined by referring centers. * Patients with evolution to AML are required to be in a complete remission as defined by a blast count of less than 5% in a marrow aspirate with adequate cellularity. Presence of residual dysplastic features following cytoreductive therapy is acceptable. * All patients with high risk disease, for example intermediate-2 or high risk disease by the IPSS score. Other selected patients with a lower IPSS score may be considered but only after discussion with the BMT attending physicians, as a group, and the PI of the study. MYELOPROLIFERATIVE DISORDERS * Myeloproliferative disorders to be included: * Philadelphia chromosome-negative CML. * Patients with polycythemia vera with persistent thrombotic or hemorrhagic complications despite conventional therapy, or who have progressed to post-polycythemic marrow fibrosis. * Patients with essential thrombocythemia with persistent thrombotic or hemorrhagic complications despite conventional therapy, or who have progressed to myelofibrosis. * Patients with agnogenic myeloid metaplasia with high risk disease, for example intermediate or high risk according to the Lille Scoring System. * Patients must be cytoreduced to \< 10% marrow blasts. Less than 10% marrow blasts must be documented by marrow examination within 1 month of initiation of TLI/ATG. The cytoreductive regimen will be determined by referring centers. * Patients with evolution to AML are required to be in a complete remission as defined by a blast count of less than 5% in a marrow aspirate with adequate cellularity. Presence of residual dysplastic features following cytoreductive therapy is acceptable. INCLUSION CRITERIA - RELATED DONORS * Related to the patient and is genotypically or phenotypically HLA-identical. * Donor age \< 75 unless cleared by P.I * Capable of giving written, informed consent. * Donor must consent to PBSC mobilization with G-CSF and apheresis INCLUSION CRITERIA - UNRELATED DONORS * Donors must be HLA-matched as defined by the following criteria: * Matched for HLA-DRB1 and DQB1 by high resolution typing. * Serologic match for all recognized HLA-A, HLA-B, and HLA-C antigens, and molecular match for at least 5 of 6 HLA-A, HLA-B, or HLA-C antigens by high resolution typing. * Donor must consent to PBSC mobilization with G-CSF and apheresis. Bone marrow unrelated donors are not eligible for this protocol.
Exclusion criteria
GENERAL
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To improve survival outcome for selected patients with advanced stages of MDS and MPD with non-myeloablative allogeneic HCT from related and unrelated donors. | 7/15/2017 |
| To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients or those with co-morbid conditions that preclude myeloablative transplantation for advanced stage MDS and MPD. | 7/15/2017 |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate myeloid and platelet engraftment. | 7/15/2017 |
| To evaluate the rate of relapse, survival and event-free survival. | 7/15/2017 |
| To evaluate the rate of primary and secondary graft failure. | 7/15/2017 |
| To evaluate the incidence of acute and chronic GVHD. | 7/15/2017 |
| To evaluate if DLI can be used safely in patients with mixed chimerism. | 7/15/2017 |
Countries
United States
Outcome results
None listed