NCT02259348

Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation

CD45A-Depleted Haploidentical Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

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.

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)

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given intravenously (IV)
DRUG	Fludarabine	Given IV
BIOLOGICAL	G-CSF	Given IV or subcutaneously (SQ)
BIOLOGICAL	Interleukin-2	Given SQ
DRUG	Melphalan	Given IV
DRUG	Thiotepa	Given IV
DRUG	Rituximab	Given IV
BIOLOGICAL	Natural killer cell therapy	Given IV
BIOLOGICAL	T-cell depleted HPC transplant	T-cell depleted hematopoietic stem cells will be infused on day 0.
BIOLOGICAL	CD45RA-depleted HPC transplant	CD45RA depleted stem cells will be infused on day 1.

Timeline

• Start date: 2014-10-01
• Primary completion: 2015-04-01
• Completion: 2016-03-01
• First posted: 2014-10-08
• Last updated: 2017-05-30
• Results posted: 2016-05-02

Locations

1 site across 1 country: United States