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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Percent of participants with positive ANC engraftment
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- — to 21 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Group A: Neuroblastoma
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.
Intervention: CD133+ selected autologous stem cell infusion (Biological)
Group A: Neuroblastoma
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.
Intervention: IL-2 (Biological)
Group A: Neuroblastoma
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.
Intervention: hu14.18K322A (Biological)
Group A: Neuroblastoma
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.
Intervention: Busulfan (Drug)
Group A: Neuroblastoma
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.
Intervention: Melphalan (Drug)
Group A: Neuroblastoma
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.
Intervention: GM-CSF (Biological)
Group A: Neuroblastoma
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.
Intervention: Haploidentical natural killer cell infusion (Device)
Group A: Neuroblastoma
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.
Intervention: G-CSF (Biological)
Group A: Neuroblastoma
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.
Intervention: CliniMACS (Device)
Group B: Lymphoma
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.
Intervention: CD133+ selected autologous stem cell infusion (Biological)
Group B: Lymphoma
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.
Intervention: IL-2 (Biological)
Group B: Lymphoma
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.
Intervention: Melphalan (Drug)
Group B: Lymphoma
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.
Intervention: GM-CSF (Biological)
Group B: Lymphoma
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.
Intervention: Bendamustine (Drug)
Group B: Lymphoma
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.
Intervention: Etoposide (Drug)
Group B: Lymphoma
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.
Intervention: Cytarabine (Drug)
Group B: Lymphoma
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.
Intervention: Haploidentical natural killer cell infusion (Device)
Group B: Lymphoma
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.
Intervention: G-CSF (Biological)
Group B: Lymphoma
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.
Intervention: Etoposide phosphate (Drug)
Group B: Lymphoma
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.
Intervention: CliniMACS (Device)
Group C: High-Risk Tumors
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.
Intervention: CD133+ selected autologous stem cell infusion (Biological)
Group C: High-Risk Tumors
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.
Intervention: IL-2 (Biological)
Group C: High-Risk Tumors
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.
Intervention: Melphalan (Drug)
Group C: High-Risk Tumors
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.
Intervention: GM-CSF (Biological)
Group C: High-Risk Tumors
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.
Intervention: Etoposide (Drug)
Group C: High-Risk Tumors
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.
Intervention: Carboplatin (Drug)
Group C: High-Risk Tumors
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.
Intervention: Haploidentical natural killer cell infusion (Device)
Group C: High-Risk Tumors
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.
Intervention: G-CSF (Biological)
Group C: High-Risk Tumors
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.
Intervention: Etoposide phosphate (Drug)
Group C: High-Risk Tumors
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.
Intervention: CliniMACS (Device)
Outcomes
Primary Outcomes
Percent of participants with positive ANC engraftment
Time Frame: 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 Outcomes
- Overall survival(Up to one year after transplantation)
- Disease-free survival(Up to one year after transplantation)
- Lymphocyte and hematopoietic reconstitution(Up to one year after transplantation)
- Characteristics of the stem cell grafts(Up to one year after transplantation)
- Characteristics of the natural killer cell grafts.(Up to one year after transplantation)
- Overall survival of patients treated without stem cell manipulation or NK cell infusion due to off therapy criteria(Up to one year after transplantation)
- Incidence of relapse(Up to one year after transplantation)