A Pilot Study of Immunotherapy Including Haploidentical NK Cell Infusion Following CD133+ Positively-Selected Autologous Hematopoietic Stem Cells in Children With High Risk Solid Tumors or Lymphomas
Phase 1
Completed
- Conditions
- NeuroblastomaLymphomaHigh-risk Tumor
- Interventions
- Biological: CD133+ selected autologous stem cell infusionBiological: IL-2Biological: hu14.18K322ABiological: GM-CSFDevice: Haploidentical natural killer cell infusionBiological: G-CSFDevice: CliniMACS
- Registration Number
- NCT02130869
- Lead Sponsor
- St. Jude Children's Research Hospital
- Brief Summary
This is a pilot clinical trial investigating the addition of haploidentical natural killer cell infusion to autologous stem cell transplantation. This intervention will be evaluated in children with high-risk solid tumors for whom autologous transplantation is indicated. Natural killer cells from a haploidentical family member will be given after high dose chemotherapy and positively selected autologous stem cells. In patients with neuroblastoma, the anti-GD2 antibody hu14.18K322A will also be given. The effect on normal hematopoietic cell recovery will be evaluated and survival of children treated with this approach will be determined.
The investigators expect to enroll 36 participants. Haploidentical family members (donors) will also be recruited to provide natural killer cells.
- Detailed Description
Primary Objective:
* To evaluate day +35 ANC engraftment in autologous stem cell transplantation for high risk pediatric malignancies after stem cell selection and immunotherapy.
Secondary Objectives
* To estimate incidence of relapse, disease-free survival and overall survival.
* To characterize lymphocyte and hematopoietic reconstitution in these patients.
* To describe the characteristics of the stem cell and natural killer cell grafts.
* To estimate the overall survival of patients treated without stem cell manipulation or NK cell infusion due to off therapy criteria
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 8
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A: Neuroblastoma IL-2 All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group A participants receive busulfan, melphalan, CD133+ selected autologous stem cell infusion, hu14.18K322A, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group A: Neuroblastoma hu14.18K322A All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group A participants receive busulfan, melphalan, CD133+ selected autologous stem cell infusion, hu14.18K322A, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group A: Neuroblastoma GM-CSF All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group A participants receive busulfan, melphalan, CD133+ selected autologous stem cell infusion, hu14.18K322A, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group A: Neuroblastoma CD133+ selected autologous stem cell infusion All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group A participants receive busulfan, melphalan, CD133+ selected autologous stem cell infusion, hu14.18K322A, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group A: Neuroblastoma Haploidentical natural killer cell infusion All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group A participants receive busulfan, melphalan, CD133+ selected autologous stem cell infusion, hu14.18K322A, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group A: Neuroblastoma G-CSF All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group A participants receive busulfan, melphalan, CD133+ selected autologous stem cell infusion, hu14.18K322A, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group A: Neuroblastoma CliniMACS All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group A participants receive busulfan, melphalan, CD133+ selected autologous stem cell infusion, hu14.18K322A, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group B: Lymphoma IL-2 All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group B: Lymphoma CD133+ selected autologous stem cell infusion All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group B: Lymphoma GM-CSF All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group B: Lymphoma Etoposide All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group B: Lymphoma Haploidentical natural killer cell infusion All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group B: Lymphoma G-CSF All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group B: Lymphoma CliniMACS All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group C: High-Risk Tumors CD133+ selected autologous stem cell infusion All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group C participants receive melphalan, etoposide (or etoposide phosphate), carboplatin, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group C: High-Risk Tumors IL-2 All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group C participants receive melphalan, etoposide (or etoposide phosphate), carboplatin, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group C: High-Risk Tumors GM-CSF All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group C participants receive melphalan, etoposide (or etoposide phosphate), carboplatin, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group C: High-Risk Tumors Haploidentical natural killer cell infusion All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group C participants receive melphalan, etoposide (or etoposide phosphate), carboplatin, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group C: High-Risk Tumors G-CSF All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group C participants receive melphalan, etoposide (or etoposide phosphate), carboplatin, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group C: High-Risk Tumors Melphalan All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group C participants receive melphalan, etoposide (or etoposide phosphate), carboplatin, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group C: High-Risk Tumors CliniMACS All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group C participants receive melphalan, etoposide (or etoposide phosphate), carboplatin, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group C: High-Risk Tumors Etoposide phosphate All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group C participants receive melphalan, etoposide (or etoposide phosphate), carboplatin, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group B: Lymphoma Etoposide phosphate All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group A: Neuroblastoma Busulfan All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group A participants receive busulfan, melphalan, CD133+ selected autologous stem cell infusion, hu14.18K322A, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group A: Neuroblastoma Melphalan All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group A participants receive busulfan, melphalan, CD133+ selected autologous stem cell infusion, hu14.18K322A, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group B: Lymphoma Melphalan All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group B: Lymphoma Cytarabine All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group B: Lymphoma Bendamustine All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group C: High-Risk Tumors Etoposide All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group C participants receive melphalan, etoposide (or etoposide phosphate), carboplatin, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System. Group C: High-Risk Tumors Carboplatin All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group C participants receive melphalan, etoposide (or etoposide phosphate), carboplatin, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF. Cells for infusion are prepared using the CliniMACS System.
- Primary Outcome Measures
Name Time Method Percent of participants with positive ANC engraftment Day 35 post transplant Feasibility will be determined based on ANC engraftment defined as ANC ≥500/mm\^3 for 3 consecutive tests performed on different days evaluated before day 35 post-transplant. If the study is considered feasible, the ANC engraftment rate will be 100% (95% Blyth-Still-Casella (BSC) CI: 76.45%-100%) without any failure, 92% (BSC 95% CI: 65.11%-99.57%) with 1 failure, and 83% (BSC 95% CI: 55%-96.95%) with 2 failures. In addition, if more than 2 (≥ 3) on-therapy patients die due to any protocol treatment-related causes during the first 12 months post-transplant across all groups (3 deaths among 36 participants), the study will be stopped. Deaths due to treatment not specified in this protocol will not be included in evaluation of this stopping rule.
- Secondary Outcome Measures
Name Time Method Overall survival Up to one year after transplantation Overall survival is defined based on any death. The Kaplan-Meier Estimate will be provided.
Disease-free survival Up to one year after transplantation Disease-free survival is defined based on any death, graft failure, or relapsed/resistant disease. The Kaplan-Meier Estimate will be provided.
Lymphocyte and hematopoietic reconstitution Up to one year after transplantation The hematopoietic cell recovery and engraftment rates will be reported with a Blyth-Still-Casella 95% confidence interval.
Characteristics of the stem cell grafts Up to one year after transplantation Results will be reported and presented descriptively.
Characteristics of the natural killer cell grafts. Up to one year after transplantation Results will be reported and presented descriptively.
Overall survival of patients treated without stem cell manipulation or NK cell infusion due to off therapy criteria Up to one year after transplantation The Kaplan-Meier estimate will be provided for overall survival analysis.
Incidence of relapse Up to one year after transplantation Cumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event.
Trial Locations
- Locations (1)
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States