Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancy's and Solid Tumors
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|ClinicalTrials.gov Identifier: NCT02508038|
Recruitment Status : Recruiting
First Posted : July 24, 2015
Last Update Posted : March 20, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Hodgkin Lymphoma Non-Hodgkin Lymphoma Myelodysplastic Syndrome Myeloproliferative Syndrome Rhabdomyosarcoma Ewing Sarcoma Primitive Neuroectodermal Tumor Osteosarcoma Neuroblastoma||Procedure: TCRαβ+/CD19+ depleted Haploidentical HSCT Drug: Zoledronate||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||January 2016|
|Estimated Primary Completion Date :||May 2021|
|Estimated Study Completion Date :||November 2023|
Experimental: TCRαβ+/CD19+ depleted Haploidentical HSCT+ Zoledronate
Patients with high-risk leukemia (who are at least one year of age and who have not received TBI as conditioning for a previous HSCT) will receive myeloablative conditioning with ATG, Gludarabine, Thiotepa, and TBI. All other subjects will undergo a reduced-intensity conditioning regimen consisting of ATG, Fludarabine, Thiotepa, and Melphalan prior to transplant with a KIR/KIR ligand mismatched haploidentical donor peripheral blood stem cell graft depleted of TCR-αβ+ and CD19+ cells. Patients will receive 5 doses of zoledronate (at 28 day intervals) starting 28 days after stem cell transplant.
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 TBI 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. All other patientw will undergo a reduced-intensity conditioning regimen consisting of ATG, Fludarabine, Thiotep and Melphalan followed by haploidentical transplant.
Given IV. Patients will receive five doses of Zoledronate (each 1.25 mg/m2 at a 28 day interval) following transplant.
- Incidence of acute graft versus host disease (GVHD) [ Time Frame: Within 100 days post-transplantation ]
- Incidence of neutrophil engraftment [ Time Frame: Up to day 28 ]Neutrophil engraftment is defined by Absolute Neutrophil Count (ANC) cell count and time to reach ANC greater than 500 for three consecutive days.
- Incidence of platelet engraftment [ Time Frame: Up to day 28 ]Platelet engraftment is as defined by platelet count and time to reach more than or equal to 20,000 for three consecutive days, without platelet transfusions for 7 days.
- Incidence of graft failure [ Time Frame: At day 28 ]
- Immune reconstitution [ Time Frame: Up to 2 years ]Immune reconstitution outcomes, as determined by immune cell analysis.
- Performance of the CliniMACS Reagent System utilizing the CliniMACS TCRαβ-biotin and CliniMACS CD19 reagent to produce a graft with defined cell content. [ Time Frame: Day 0 ]The performance of the CliniMACS Reagent System will be evaluated by measuring the number of viable stem cells, TCRαβ+ cells, TCRγδ+ cells, NK cells and B cells in the hematopoietic stem cell graft.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02508038
|Contact: Jenny Weiland||608-890-8070||PedsHemOncResearch@lists.wisc.edu|
|Contact: Celeste Matsushima||608-890-8069|
|United States, Wisconsin|
|University of Wisconsin Carbone Cancer Center||Recruiting|
|Madison, Wisconsin, United States, 53705|
|Contact: Pediatric HemOnc Main Line 608-263-6200 PEDSHemOncResearch@lists.wisc.edu|
|Contact: Research Office 608-890-8070 PEDSHemOncResearch@lists.wisc.edu|
|Principal Investigator: Mario Otto, MD, PhD|
|Principal Investigator:||Mario Otto, MD, PhD||University of Wisconsin, Madison|