Haploidentical Donor Hematopoietic Progenitor Cell and NK Cell Transplantation for Hematologic Malignancy
- Conditions
- LeukemiaLymphoma
- Interventions
- Radiation: Total Lymphoid IrradiationBiological: HPC,A InfusionBiological: TC-NK InfusionBiological: G-CSFDevice: CliniMACS
- Registration Number
- NCT01807611
- Lead Sponsor
- St. Jude Children's Research Hospital
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 82
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Transplant Recipients Total Lymphoid Irradiation Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System. Transplant Recipients Fludarabine Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System. Transplant Recipients HPC,A Infusion Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System. Transplant Recipients TC-NK Infusion Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System. Transplant Recipients G-CSF Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System. Transplant Recipients Mesna Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System. Transplant Recipients CliniMACS Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System. Transplant Recipients Mycophenolate mofetil Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System. Transplant Recipients Thiotepa Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System. Transplant Recipients Cyclophosphamide Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System. Transplant Recipients Melphalan Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System.
- Primary Outcome Measures
Name Time Method Number of Transplant Recipients With Successful Engraftment 42 days post engraftment Neutrophil engraftment will be determined using the parameters put forth by the Center for International Blood and Marrow Registry. Assessments will be made upon review of daily complete blood count and serial chimerism studies. Successful engraftment for the purposes of this objective will be patients who do not experience graft failure.
- Secondary Outcome Measures
Name Time Method Number of Transplant Recipients With Malignant Relapse One-year post-transplantation Bone marrow studies for disease status evaluation will be performed at 1-year post-transplant. Testing will include a research evaluation for minimal residual disease.
Overall Survival one year post-transplantation The one-year survival is defined by the patient who has not died within one year after post transplantation. And the rate is calculated by computing the ratio between total number of one year survival patients and the total number of patients.
Event-free Survival One year post-transplantation The one-year event free survival is defined by the patient who has neither experienced relapse nor death within one year after post transplantation. And the rate is calculated by computing the ratio between total number of one year event free survival patients and the total number of patients.
Number of Transplant Recipients With Acute and/or Chronic Graft Versus Host Disease (GVHD) 100 days post-transplant for acute GVHD; one year post-transplant for chronic GVHD . Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The estimate will be the number of recipients who experienced GVHD divided by the total number of patients considered in this group.
Severity of Chronic Graft Versus Host Disease (cGVHD) 1 year post-transplant for chronic GVHD . Ongoing assessment of toxicity will be done using the NCI CTCAE version 3.0. Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The severity of acute GvHD and chronic GvHD will be described. The analysis for this objective will be performed when the last evaluable participant has been followed for 1 year post-transplant. Chronic GvHD is graded as "mild", "moderate" or "severe" with "severe" being the worst outcome.
Number of Transplant Recipients With Transplant-related Mortality (TRM) In the first 100 days after transplantation Estimate the proportion of patients died within 100 days after the transplantation who has not experienced a relapse. The estimate will be the number of TRM divides the total number of patients considered in this group.
Severity of Acute Graft Versus Host Disease (aGVHD) 100 days post-transplant for acute GVHD. Ongoing assessment of toxicity will be done using the NCI CTCAE version 3.0. Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The severity of acute GvHD and chronic GvHD will be described. The analysis for this objective will be performed when the last evaluable participant has been followed for 100 days post transplant. Acute GvHD is graded from 1-4 with 4 being the worst outcome.
Trial Locations
- Locations (1)
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States