NCT02199041

Combined T Cell Depleted Haploidentical Peripheral Blood Stem Cell and Unrelated Umbilical Cord Blood Transplantation in Patients With Hematologic Malignancies Using a Total Lymphoid Irradiation Based Preparative Regimen

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (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), matched unrelated donor (MURD) or killer-immunoglobulin receptors (KIR) ligand mismatched haploidentical donor identified, will receive a combined T cell depleted (TCD) haploidentical peripheral blood stem cell (PBSC) and unrelated umbilical cord blood transplantation (UCBT) using a total lymphoid irradiation (TLI) based preparative regimen. Primary objective: * To estimate the incidence of donor derived neutrophil engraftment by day +42 post-transplant for participants with high-risk hematologic malignancies undergoing a total lymphoid irradiation (TLI)-based hematopoietic cell transplantation (HCT) using a T cell depleted (TCI) haploidentical donor peripheral blood stem cell (PBSC) donor combined with an unrelated umbilical cord blood (UCB) donor. Secondary objectives: * Estimate the incidence of malignant relapse, event-free survival (EFS), and overall survival (OS) at one-year post-transplantation. * Estimate the incidence and severity of acute and chronic graft versus host disease (GVHD) in the first 100 days after transplantation. * Estimate the incidence of secondary graft failure transplant related mortality (TRM) and transplant related morbidity in the first 100 days after HCT.

Detailed description

Prior to stem cell infusion, participants will receive a preparative regimen of total lymphoid irradiation (TLI), fludarabine, cyclophosphamide, melphalan, and thiotepa to prepare their bone marrow. Thereafter, they will receive a hematopoietic cell graft from a haploidentical donor and an unrelated umbilical cord blood donor. Post-transplantation immunosuppressive treatment will include tacrolimus and mycophenolate mofetil.

Conditions

• Hematological Malignancies

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given by intravenous infusion as part of the preparative regimen.
DRUG	Thiotepa	Given by intravenous infusion as part of the preparative regimen.
DRUG	Fludarabine	Given by intravenous infusion as part of the preparative regimen.
DRUG	Melphalan	Given by intravenous infusion as part of the preparative regimen.
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.
BIOLOGICAL	G-CSF	Given either by intravenous infusion or subcutaneously daily until absolute neutrophil count (ANC) \>2000 for 3 consecutive days.
DRUG	Mycophenolate mofetil	Given either orally or by intravenous infusion as part of the post-transplantation immunosuppression.
DRUG	Tacrolimus	Given either orally or by intravenous infusion as part of the post-transplantation immunosuppression.
DRUG	Methylprednisolone	Given either intravenously or orally, if needed to treat graft-versus-host-disease (GVHD).
RADIATION	Total lymphoid irradiation	TLI will be administered in divided fractions given at a minimum of 6 hours apart.
BIOLOGICAL	Lymphocyte infusions	Donors will undergo haploidentical mobilization with G-CSF. Cells will be collected by leukapheresis over two days, then processed using the investigational CliniMACS device and CD34 Microbead reagent as directed by the manufacturer.
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.

Timeline

• Start date: 2014-07-11
• Primary completion: 2017-05-23
• Completion: 2017-05-23
• First posted: 2014-07-24
• Last updated: 2018-02-07
• Results posted: 2018-02-07

Locations

1 site across 1 country: United States

Regulatory

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