This phase I trial studies how well reduced intensity chemotherapy and total-body irradiation before allogeneic TCR alpha/beta-positive T-lymphocyte-depleted peripheral blood stem cells (TCR-alpha/beta+ T-lymphocytes donor transplant) works in treating participants with high-risk myeloid diseases. Giving chemotherapy such as anti-thymocyte globulin and fludarabine phosphate, as well as total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the participant's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the participant they may help the participant's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Removing the T cells from the donor cells before the transplant may stop this from happening.
Additional locations may be listed on ClinicalTrials.gov for NCT03531736.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To assess the ability to achieve a sustained full donor myeloid engraftment after using a T cell depleted graft from matched related or unrelated donor and a reduced intensity conditioning regimen in patients with myeloid malignancies.
SECONDARY OBJECTIVES:
I. Subset chimerism at days +30, +60 +100, +180 and at 1, 1.5 and 2 years post-hematopoietic cell transplantation (HCT).
II. Counts recovery (platelet [PLT] > 20,000 and hemoglobin [Hb] > 8) at days 30 and 100 post-HCT.
III. Overall survival at 2 years post-transplant.
IV. Incidence of relapse at 2 years post-transplant.
V. Incidence of non-relapsed mortality at 2 years post-transplant.
VI. Incidence of viral infection and disease at day 100 and at 1 year post-transplant (specifically cytomegalovirus [CMV] reactivation and disease and Epstein-Barr virus [EBV] reactivation and EBV-post-transplant lymphoproliferative disease [PTLD]).
VII. Incidence and severity of chronic graft versus host disease (GVHD) at 2 year post-transplant.
VIII. Incidence and severity of acute GVHD at 100 days and at 1 year post-transplant.
IX. Immune recovery after transplant at days 100, 180 and at 1 year post-transplant.
X. Assess toxicities early (first 100 days) and late (> 100 days) post-transplant.
CORRELATIVE OBJECTIVES:
I. Assess T cell response to viruses that are commonly reactivated post allo-HSCT, i.e. CMV, EBV and adenovirus.
II. Assess reconstitution of TCR-alpha/beta+ T-lymphocytes after T-cell receptor (TCR)-alpha/beta+ lymphocyte depleted allografts at days +100, +180 and at 1 year post transplantation.
III. Assess for residual disease post allo-HSCT by using a panel of aberrantly expressed cell surface proteins that are highly specific and sensitive for the detection of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML).
OUTLINE:
REDUCED INTENSITY CONDITIONING: Participants receive anti-thymocyte globulin intravenously (IV) over 30 minutes once daily (QD) on days -8 to -6, fludarabine phosphate IV over 30 minutes on days -5 to -2, and undergo total body irradiation (TBI) over 20-30 minutes on days -2 and -1.
TRANSPLANT: Participants receive allogeneic TCR alpha/beta-positive T-lymphocyte-depleted peripheral blood stem cells on days 0.
POST-TRANSPLANT: Participants receive cyclophosphamide IV over 30 minutes on days 3-4 and rituximab IV over 90 minutes on day 5.
After completion of transplant, participants are followed up at 30, 60, and 100 days, at 6, 9, 12, 18, and 24 months, and then yearly for 5 years.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorRoni Tamari