Hematopoietic stem cell transplantation can cure patients with blood cancer and other underlying diseases. αβ-T cell and B cell depletion has been introduced to decrease GVHD and PTLD and has demonstrated effectiveness for hematologic malignancies and non-malignant diseases additionally increasing the donor pool as to allow for haploidentical transplant to safely occur.
While solid tumors can be highly chemotherapy sensitive, many remain resistant and require multimodalities of treatment. Immunotherapy has been developed to harness the immune system in fighting solid tumors, though not all have targeted effects. Some solid tumors are treated with autologous transplants; however, they do not always demonstrate an improved event free survival or overall survival. There has been evidence of the use of allogeneic stem cell transplants to provide a graft versus tumor effect, though studies remain limited.
By utilizing αβ-T cell and B cell depletion for stem cell transplants and combining with zoledronic acid, the immune system may potentially be harnessed and enhanced to provide an improved graft versus tumor effect in relapsed/refractory solid tumors and promote an improved event-free survival and overall survival.
This study will investigate the safety of treatment with a stem cell graft depleted of αβ-T cell and CD19+ B cells in combination with zoledronic acid in pediatric and young adult patients with select solid tumors, as well as whether this treatment improves survival rates in these patients.
Patients 6 months to ≤ 25 years old
neuroblastoma (high risk with relapsed or refractory disease),
relapsed/refractory rhabdomyosarcoma,
relapsed/refractory non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): synovial sarcoma, malignant peripheral nerve sheath tumors (MPNST),
Patients with documented uncontrolled infection at the time of study entry are not eligible.
Patients with progressive solid tumor disease after relapsed/refractory treatment.
Demonstrated lack of compliance with medical care, as determined by the treating physician.
Patients who have received an allogeneic HSCT within 6 months.
Sequential
Miltenyi CliniMACS Prodigy ® system
DeviceSubjects will receive an allogeneic stem cell transplant that has been depleted of ⍺/β T-cells and CD19+ B-cells using the Miltenyi CliniMACS Prodigy® system.
Zoledronic acid
DrugAll subjects will receive zoledronic acid intravenously on days +28, +56, +84, +112, and +140. Dosing in the phase Ib portion of the study will follow a 3 + 3 design where the first 3 subjects will receive the expected phase II dose of 1.25 mg/m2 (dose level 1). If no dose-limiting toxicities (DLTs) occur in these subjects, dose level 1 will be the maximum tolerated dose. However, if at least 1 DLT is observed in the first 3 patients, 3 additional subjects will be enrolled at dose level 1. If more than 2 DLTs are observed in these 6 subjects, then dose de-escalation to 0.8 mg/m2 (dose level 0) will occur and 3-6 additional subjects may be enrolled. All subjects in the phase II portion of the study will receive the maximum tolerated dose determined in the phase Ib portion.
Disease-free survival rate
Determine the disease-free survival rate at 1 year post-transplant
Incidence of aGVHD
Determine the incidence of grade II-IV acute graft versus host disease (aGVHD)
Disease-free survival rate
Determine the disease-free survival rate at 100 days post-transplant
Disease-free survival rate
Determine the disease-free survival rate at 2 years post-transplant
Overall survival rate
Determine the overall survival rate at 100 days post-transplant
Overall survival rate
Determine the overall survival rate at 1 year post-transplant
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University of Florida
Lead sponsor
Ocala Royal Dames for Cancer Research
Collaborator
Florida Department of Health
Collaborator
