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

NCT02508038 | Recruiting Phase 1 DMC

• 6 other identifiers: UW13090NCI-2015-011632015-0290A536700SMPH\PEDIATRICS\PEDIATRICSProtocol Version 10/12/2021
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

alpha beta depleted; alphabeta; TCR alpha beta depleted; alpha beta; haploidentical; Zoledronate; Zoledronic acid; Pediatric cancers; alfa beta; αβ T cell depleted HSCT; alpha beta T cell and B cell depleted HSCT; haploidentical HSCT

Outcome Measures

Primary Outcomes (2)

• Incidence of acute graft versus host disease (GVHD)

  Within 100 days post-transplantation

• Incidence of graft failure

  At day 28

Secondary Outcomes (2)

• Immune reconstitution

  Up to 1 year

• Performance of the CliniMACS Reagent System utilizing the CliniMACS TCRαβ-biotin and CliniMACS CD19 reagent to produce a graft with defined cell content.

  Day 0

Study Arms (1)

TCRαβ+/CD19+ depleted Haploidentical HSCT+ Zoledronate

EXPERIMENTAL

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, Fludarabine, 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; Drug: Zoledronate

Interventions

TCRαβ+/CD19+ depleted Haploidentical HSCT PROCEDURE

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.

TCRαβ+/CD19+ depleted Haploidentical HSCT+ Zoledronate

Zoledronate DRUG

Given IV. Patients will receive five doses of Zoledronate (each 1.25 mg/m2 at a 28 day interval) following transplant.

Also known as: Zoledronic Acid, Zometa

TCRαβ+/CD19+ depleted Haploidentical HSCT+ Zoledronate

Eligibility Criteria

• Age: 7 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Availability of an eligible haploidentical donor
• Hematologic malignancy or solid tumor
• Patients with more than one malignancy (hematologic or solid tumor) are eligible
• Patients with hematologic malignancy must have no HLA identical sibling or suitable unrelated donor OR time needed to find an acceptable unrelated donor match would likely result in disease progression such that the patient may become ineligible for any type of potentially curative transplant
• Relapsed or primary therapy-refractory AML with bone marrow blast \< 20%
• High-risk refractory or relapsed ALL in patients for whom transplantation is deemed indicated (relapse occurring \< 30 months from diagnosis, patients relapsing after previous allogeneic transplant, relapse after 2nd remission, primary induction failure or hypodiploidy)
• Relapsed Hodgkin lymphoma unable to achieve 2nd remission or Very Good Partial Response (VGPR) and therefore ineligible to receive autologous hematopoietic stem cell transplant (auto-HSCT)
• Hodgkin lymphoma relapsing after auto-HSCT
• Primary refractory or relapsed non-Hodgkin lymphoma unable to achieve 2nd remission or VGPR and therefore ineligible to receive auto-HSCT
• Non-Hodgkin lymphoma relapsing after auto-HSCT
• Myelodysplastic Syndrome/Myeloproliferative Syndrome
• Solid Tumor
• Patients with solid tumor must have failed or have been ineligible to receive auto-HSCT or if auto-HSCT would not offer \> 20% chance of cure
• Neuroblastoma
• high risk with relapsed or refractory disease

You may not qualify if:

• Pregnant or breast-feeding
• HIV infection
• Heart failure or uncontrolled cardiac rhythm disturbance
• Uncontrolled, Serious Active Infection
• Prior organ allograft
• Any mental or physical condition, in the opinion of the PI (or PI designee), which could interfere with the ability of the subject (or the only parent or legal guardian available to care for the subject) to understand or adhere to the requirements of the study
• Enrollment in any other clinical study from screening up to Day 100 (unless PI judges such enrollment would not interfere with endpoints of this study)
• Lactating females
• Pregnant females

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53705, United States

RECRUITING

Related Publications (1)

• Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

  PMID: 31401903 DERIVED

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes; Rhabdomyosarcoma; Sarcoma, Ewing; Neuroectodermal Tumors, Primitive; Osteosarcoma; Neuroblastoma

Interventions

Zoledronic Acid

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Bone Marrow Diseases; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive, Peripheral

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Christian Capitini, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jenny Weiland

CONTACT

608-890-8070; PedsHemOncResearch@g-groups.wisc.edu

Celeste Matsushima

CONTACT

608-890-8069

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2015
• First Posted: July 24, 2015
• Study Start: February 12, 2016
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 16, 2025

Record last verified: 2025-10

Locations

US (1)