NCT01807611

Haploidentical Donor Hematopoietic Progenitor Cell and NK Cell Transplantation for Hematologic Malignancy

Haploidentical Donor Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation With a TLI Based Conditioning Regimen in Patients With Hematologic Malignancies

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 82 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA) matched related/sibling donor (MSD) or matched unrelated donor (MUD) identified, will receive a haploidentical donor HCT with additional natural killer (NK) cells. The investigators anticipate enrollment of 75 donors and 75 recipients. PRIMARY OBJECTIVE: * To estimate the rate of successful engraftment at day +42 post-transplant in patients who receive haploidentical donor stem cell plus NK cell transplantation with TLI based conditioning regimen for high risk hematologic malignancy. 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.

Detailed description

Donors will undergo G-CSF mobilization of peripheral blood stem cells (PBSC) prior to undergoing two apheresis collections of hematopoietic progenitor cells (HPC,A) and one apheresis collection of therapeutic cell product of purified natural killer cells (TC-NK). The HPC products will be T-cell depleted (TCD) using the investigational CliniMACS device. CD34+ enrichment and CD45RA depletion will be utilized on sequential HPC grafts. Participants will undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, granulocyte colony stimulating factor (G-CSF), thiotepa, and melphalan. This is followed by infusions of donor cells that have been prepared using the CliniMACS system: HPC,A (CD34+ selected), HPC,A (CD45RA depleted), and TC-NK.

Conditions

• Leukemia
• Lymphoma

Interventions

Type	Name	Description
RADIATION	Total Lymphoid Irradiation	Participants receive total lymphoid irradiation over four doses.
DRUG	Fludarabine	Given IV.
DRUG	Cyclophosphamide	Given IV.
DRUG	Thiotepa	Given IV.
DRUG	Melphalan	Given IV.
BIOLOGICAL	HPC,A Infusion	Participants received infusions of HPC,A (CD34+ selected) and HPC,A (CD45RA depleted).
BIOLOGICAL	TC-NK Infusion	Participants receive infusions of TC-NK.
BIOLOGICAL	G-CSF	Participants receive G-CSF subcutaneously or intravenously. Donors receive G-CSF subcutaneously during cell mobilization.
DRUG	Mesna	Mesna is generally dosed at approximately 25% of the cyclophosphamide dose. It is generally given intravenously prior to and again at 3, 6 and 9 hours following each dose of cyclophosphamide.
DEVICE	CliniMACS	The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
DRUG	Mycophenolate mofetil	Given intravenously or orally.

Timeline

• Start date: 2013-05-16
• Primary completion: 2021-08-27
• Completion: 2021-09-27
• First posted: 2013-03-08
• Last updated: 2022-10-31
• Results posted: 2022-10-31

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study