TCRαβ+/CD19+ Depleted Haploidentical HSCT + Zoledronate
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|ClinicalTrials.gov Identifier: NCT02508038|
Recruitment Status : Recruiting
First Posted : July 24, 2015
Last Update Posted : April 19, 2017
|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|
REDUCED-INTENSITY CONDITIONING REGIMEN: Patients receive anti-thymocyte globulin (ATG) intravenously (IV) on days -12 to -9, fludarabine phosphate IV on days -8 to -5, thiotepa IV twice daily (BID) on day -4, and melphalan IV on days -3 to -2.
PERIPHERAL BLOOD STEM CELL TRANSPLANTATION: Patients undergo TCR-αβ+ and CD19+ depleted haploidentical donor peripheral blood stem cell transplantation on day 0.
ZOLEDRONATE ADMINISTRATION: Patients receive zoledronate IV after transplant as determined by their assigned treatment group (Cohort). Patients in Cohort A do not receive zoledronate.
Follow-up assessments will occur after transplantation.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 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 2018|
|Estimated Study Completion Date :||November 2020|
Experimental: TCRαβ+/CD19+ depleted Haplo-HSCT+ Zoledronate
Patients 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 (except those in Cohort A) will receive two doses of Zoledronate (at a 28 day interval) following transplant. Dose and post-transplant timing of Zoledronate administration is dependent upon patient Cohort.
Procedure: TCRαβ+/CD19+ depleted Haploidentical HSCT
Patients will undergo a reduced-intensity conditioning regimen prior to transplant with a haploidentical donor peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells using the CliniMACS System.Drug: Zoledronate
Given IV. Patients (except those in Cohort A) will receive two doses of Zoledronate (at a 28 day interval) following transplant. Dose and post-transplant timing of Zoledronate administration is dependent upon patient Cohort.
- 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 ]
- Determination of Maximal Tolerated Dose (MTD) of zoledronic acid in the post-HSCT period [ Time Frame: Up to day 119 ]
- 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.
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|