Clinical trial NCT02259348
Conditions: Acute Lymphoblastic Leukemia (ALL) Acute Myeloid Leukemia (AML) Myeloid Sarcoma Chronic Myelogenous Leukemia (CML) Juvenile Myelomonocytic Leukemia (JMML) Myelodysplastic Syndrome (MDS) Non-Hodgkin Lymphoma (NHL)
Keywords: Hematological malignancies Allogeneic hematopoietic cell transplant Refractory hematologic malignancy Relapsed hematologic malignancy
Sponsor: St. Jude Children's Research Hospital
Start date: 2014-10-01; Completion date: 2016-03-01
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This pilot phase II trial studies how well a new reduced intensity conditioning regimen that includes haploidentical donor NK cells followed by the infusion of selectively T-cell depleted progenitor cell grafts work in treating younger patients with hematologic malignancies that have returned after or did not respond to treatment with a prior transplant. Giving chemotherapy and natural killer cells before a donor progenitor cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (progenitor cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy progenitor cells from a related donor are infused into the patient they make 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 specific T cells from the donor cells before the transplant may prevent this.

Detailed description:
PRIMARY OBJECTIVE:

* To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical natural killer (NK) cells.

SECONDARY OBJECTIVES:

* Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation.
* Estimate incidence and severity of acute and chronic (GvHD).
* Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.

Blood progenitor cells will be collected from adult donors to be used for transplantation. Donor cells will be processed and filtered in a laboratory at St. Jude using a machine called the CliniMACS™ device, and later infused (transplanted) into the participant through his/her veins.

Participants undergo a conditioning regimen beginning Day 21 prior to progenitor cell transplantation that includes chemotherapy medications and natural killer cells in preparation for transplantation. They will then receive T-cell depleted HPC transplant followed by CD45RA-depleted HPC transplant the following day.

Arms: arm 1: Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
Interventions: intervention 1: Cyclophosphamide intervention 2: Fludarabine intervention 3: G-CSF intervention 4: Interleukin-2 intervention 5: Melphalan intervention 6: Thiotepa intervention 7: Rituximab intervention 8: Natural killer cell therapy intervention 9: T-cell depleted HPC transplant intervention 10: CD45RA-depleted HPC transplant
Intervention descriptions: intervention 1: Given intravenously (IV) intervention 2: Given IV intervention 3: Given IV or subcutaneously (SQ) intervention 4: Given SQ intervention 5: Given IV intervention 6: Given IV intervention 7: Given IV intervention 8: Given IV intervention 9: T-cell depleted hematopoietic stem cells will be infused on day 0. intervention 10: CD45RA depleted stem cells will be infused on day 1.

Protocol documents: