TCRαβ+/CD19+ Depleted Haploidentical HSCT + Zoledronate
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02508038|
Recruitment Status : Recruiting
First Posted : July 24, 2015
Last Update Posted : May 15, 2018
|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 2021|
|Estimated Study Completion Date :||November 2023|
Experimental: TCRαβ+/CD19+ depleted Haploidentical 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 consisting of ATG (anti-thymocyte globulin), Fludarabine, Thiotepa, and Melphalan prior to transplant with a KIR/KIR (Killer cell immunoglobulin-like receptor) ligand mismatched 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|