This phase II pilot clinical trial studies how well donor T cell receptor (TCR) alpha-beta and cluster of differentiation (CD) 19-depleted (removed) stem cell transplant works in treating patients with lymphoma that has come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Chemotherapy and radiation therapy are given before transplant to help make room in the bone marrow for transplanted cells and kill any remaining cancer cells. They may also help stop the patient's immune system from rejecting the donor's stem cells. Before the donor's stem cells are infused into the patient, TCR alpha-beta and CD19 cells are removed. These cells are thought to cause graft-versus-host disease, a condition in which the transplanted cells make an immune response against the body's normal cells. Giving chemotherapy before transplant and removing TCR alpha-beta and CD19 cells from the stem cell graft may help improve the outcome of the transplant and result in lower rates of graft-versus host disease.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02652468.
PRIMARY OBJECTIVE:
I. To determine engraftment at 28 days after transplantation following TCR alpha/beta and CD19 cell depletion using peripheral blood stem cells from a human leukocyte antigen (HLA)-haploidentical donor.
SECONDARY OBJECTIVES:
I. The cumulative incidence of grade III – IV acute graft-versus-host disease (GVHD) by day +100 will be determined. The GVHD grade will be determined by the International Bone Marrow Transplant Registry (IBMTR) Severity Index criteria.
II. The cumulative incidence of severe chronic GVHD by day +180 will be recorded and defined according to the National Institutes of Health (NIH) consensus criteria.
III. Graft failure rate – defined as < 5% donor chimerism in the CD3 and/or CD33 selected cell populations at any time in the study follow up period once initial engraftment has been achieved.
IV. Treatment-related mortality rate – defined as death from any cause other than disease progression.
V. Progression-free survival – defined as time before any progression by either positron emission tomography (PET)/computed tomography (CT) or bone marrow.
VI. Overall survival – after enrollment on study.
OUTLINE:
PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over approximately 30 minutes on days -5 to -2, and mesna IV over 24 hours and cyclophosphamide IV over approximately 2 hours on days -5 and -4. Patients also undergo total nodal irradiation on day -1.
TRANSPLANT: Patients undergo TCR alpha-beta/CD19 depleted hematopoietic stem cell transplant on day 0. If the graft contains less than 4 x 10^6 CD34+ cells/kg patient body weight (BW), patients may receive a second graft on day 1.
GVHD PROPHYLAXIS: Patients receive mycophenolate mofetil orally (PO) twice daily (BID) on days -1 to 30, tacrolimus PO or IV on days 2-180 with a taper beginning on day 90 (given only if graft TCR alpha-beta+ cell content is over 1 x 10^5 cells/kg ideal BW of the patient), and rituximab IV on day 2 (given only if graft B cell content exceeds 1 x 10^5 cells/kg ideal BW of the patient).
After completion of study treatment, patients are followed up weekly for 3 months, then every 3 months up to 1 year and then every 6 months up to 2 years.
Lead OrganizationUniversity of Wisconsin Carbone Cancer Center - University Hospital
Principal InvestigatorVaishalee Padgaonkar Kenkre