This pilot phase I trial studies overall health status and how disease responds to a stem cell transplant when followed with a couple of doses of a drug called cyclophosphamide in patients with acute myeloid leukemia that has returned after all signs and symptoms of cancer have disappeared, although cancer may still be in the body (complete remission) or that has never fully responded to therapy. An allogeneic stem cell transplant is a procedure in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical, donor. This is often a sister or brother, but could be an unrelated donor. When a patient cannot find a donor who exactly matches their tissue type, half-matched related (haploidentical) donors, who are first degree relatives such as siblings, children, or parents, may be used. People who undergo a stem cell transplant can experience complications such as rejection of the stem cell transplant or severe graft-versus host disease (GVHD). Giving cyclophosphamide after haploidentical stem cell transplant may improve the outcomes of the transplant.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02057770.
PRIMARY OBJECTIVES:
I. To determine the rate of event-free survival (EFS) at 100 days post-transplantation in patients with active acute myeloid leukemia (AML) at the time of transplantation.
SECONDARY OBJECTIVES:
I. To determine the rate of overall survival (OS) at 1 year post-transplantation in patients with active AML at the time of transplantation.
II. To determine the rate of leukemia-free survival (LFS) at 100 days post-transplantation in patients with active AML at the time of transplantation (for patients who achieve complete remission [CR], cytogenic complete remission [CRc], or complete remission with incomplete blood count recovery [CRi] only).
III. To determine the transplant-related mortality (TRM) rate in patients with active AML who undergo transplantation.
IV. To determine the time to neutrophil engraftment in patients with active AML who undergo transplantation.
V. To determine the time to platelet engraftment in patients with active AML who undergo transplantation.
VI. To determine the incidence and severity of acute and chronic GVHD in patients with active AML who undergo transplantation.
VII. To investigate the rate of cytokine release syndrome with and without tocilizumab prophylaxis in patients with active AML who undergo haploidentical transplantation.
OUTLINE: Patients receive one of the following preparative regimens at the discretion of the treating physician.
BUSULFAN AND FLUDARABINE BASED PREPARATIVE REGIMEN: Patients receive busulfan intravenously (IV) over 3 hours on days -7 to -4, fludarabine phosphate IV over 30-60 minutes on days -6 to -2, and cyclophosphamide IV over 60 minutes on days -3 and -2.
FLUDARABINE AND TOTAL-BODY IRRADIATION (TBI) BASED PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -4 and undergo TBI twice daily (BID) on days -3 to 0.
DONOR CELL INFUSION: Patients undergo HLA-matched sibling, HLA-matched unrelated, or HLA-haploidentical donor stem cell transplant on day 0.
POST-TRANSPLANT CYCLOPHOSPHAMIDE: Patients receive cyclophosphamide IV over 90 minutes on days 3 and 4.
GVHD PROPHYLAXIS: Patients receive mycophenolate mofetil on days 5 to 35. HLA-haploidentical transplant recipients also receive tacrolimus on day 5 to 35. Following day 35, GVHD prophylaxis will continue at the discretion of the treating physician.
After completion of study treatment, patients are followed up for up to 48 months.
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorTodd A. Fehniger
