NCT02508038

Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors

TCR-αβ+ and CD19+ Depleted KIR/KIR Ligand-mismatched Haploidentical Hematopoietic Stem Cell Transplant and Zoledronate for Pediatric Relapsed/Refractory Hematologic Malignancies and High Risk Solid Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 22 (estimated)
• Sponsor: University of Wisconsin, Madison · Academic / Other
• Sex: All
• Age: 7 Months – 21 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the safety of transplantation with a haploidentical donor peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells in conjunction with the immunomodulating drug, Zoledronate, given in the post-transplant period to treat pediatric patients with relapsed or refractory hematologic malignancies or high risk solid tumors.

Detailed description

CONDITIONING REGIMENS: Patients with high-risk leukemia will receive myeloablative conditioning with anti-thymocyte globulin intravenously (IV) over 4-6 hours on days -12 through -9, Fludarabine IV over 30 minutes on days -8 through -5, Thiotepa IV every every 12 hours on day -4 and Total Body Irradiation (TBI) on days -3 through -1. All other patients receive reduced intensity conditioning consisting of anti-thymocyte globulin intravenously (IV) over 4-6 hours on days -12 through -9, fludarabine IV over 30 minutes on days -8 through -5, thiotepa IV over 4 hours every 12 hours on day -4, and melphalan IV on days -3 and -2. PERIPHERAL BLOOD STEM CELL TRANSPLANTATION: Patients undergo TCR-alpha/beta+ and CD19+ depleted KIR/KIR ligand-mismatched haploidentical donor peripheral blood stem cell transplantation on day 0. If the graft contains less than 4 x 10\^6 CD34+ cells/kg, a second HSC graft may be administered. PROPHYLAXIS FOR GVHD: Patients receiving a graft containing \> 25 x 10\^3 CD3+ TCR alpha/beta+ cells receive mycophenolate mofetil IV twice daily over 2 hours on days 1 to 30 with a rapid taper. Patients with TCR alpha/beta+ cells exceeding 100,000/kg also receive tacrolimus IV continuously or orally (PO) every 12 hours on days 0-90 with a taper at the discretion of the Principal Investigator. ZOLEDRONATE ADMINISTRATION: Patients will receive five doses of Zoledronate (IV) at 28 day intervals beginning on Day +28 post-HSCT. Follow-up assessments will occur after transplantation.

Conditions

• Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia
• Hodgkin Lymphoma
• Non-Hodgkin Lymphoma
• Myelodysplastic Syndrome
• Myeloproliferative Syndrome
• Rhabdomyosarcoma
• Ewing Sarcoma
• Primitive Neuroectodermal Tumor
• Osteosarcoma
• Neuroblastoma

Interventions

Type	Name	Description
PROCEDURE	TCRαβ+/CD19+ depleted Haploidentical HSCT	Patients with high-risk leukemia will receive myeloablative conditioning. All other patients will undergo a reduced-intensity conditioning with ATG, Fludarabine, Thiotepa and Melphalan followed by transplant with a KIR/KIR (Killer cell immunoglobulin-like recetptor) ligand mismatched haploidentical donor peripheral blood stem cell graft depleted of TCRab+ cells and CD19+ cells using the CliniMACS System.
DRUG	Zoledronate	Given IV. Patients will receive five doses of Zoledronate (each 1.25 mg/m2 at a 28 day interval) following transplant.

Timeline

• Start date: 2016-02-12
• Primary completion: 2026-12-01
• Completion: 2027-12-01
• First posted: 2015-07-24
• Last updated: 2025-10-16

Locations

1 site across 1 country: United States