Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors

NCT ID: NCT06625190

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-28

Study Completion Date

2030-02-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Hematopoietic stem cell transplantation can cure patients with blood cancer and other underlying diseases. αβ-T cell and B cell depletion has been introduced to decrease GVHD and PTLD and has demonstrated effectiveness for hematologic malignancies and non-malignant diseases additionally increasing the donor pool as to allow for haploidentical transplant to safely occur.

While solid tumors can be highly chemotherapy sensitive, many remain resistant and require multimodalities of treatment. Immunotherapy has been developed to harness the immune system in fighting solid tumors, though not all have targeted effects. Some solid tumors are treated with autologous transplants; however, they do not always demonstrate an improved event free survival or overall survival. There has been evidence of the use of allogeneic stem cell transplants to provide a graft versus tumor effect, though studies remain limited.

By utilizing αβ-T cell and B cell depletion for stem cell transplants and combining with zoledronic acid, the immune system may potentially be harnessed and enhanced to provide an improved graft versus tumor effect in relapsed/refractory solid tumors and promote an improved event-free survival and overall survival.

This study will investigate the safety of treatment with a stem cell graft depleted of αβ-T cell and CD19+ B cells in combination with zoledronic acid in pediatric and young adult patients with select solid tumors, as well as whether this treatment improves survival rates in these patients.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Neuroblastoma Rhabdomyosarcoma Synovial Sarcoma Peripheral Nerve Sheath Tumors Clear Cell Sarcoma Alveolar Soft Part Sarcoma Desmoplastic Small Round Cell Tumor Chordoma Rhabdoid Tumor Epithelioid Sarcoma Myoepithelial Tumor Osteosarcoma Ewing Sarcoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

alpha/beta T cell and CD19+ B cell depleted stem cell graft with zoledronic acid

Group Type EXPERIMENTAL

Miltenyi CliniMACS Prodigy ® system

Intervention Type DEVICE

Subjects will receive an allogeneic stem cell transplant that has been depleted of ⍺/β T-cells and CD19+ B-cells using the Miltenyi CliniMACS Prodigy® system.

Zoledronic acid

Intervention Type DRUG

All subjects will receive zoledronic acid intravenously on days +28, +56, +84, +112, and +140.

Dosing in the phase Ib portion of the study will follow a 3 + 3 design where the first 3 subjects will receive the expected phase II dose of 1.25 mg/m2 (dose level 1). If no dose-limiting toxicities (DLTs) occur in these subjects, dose level 1 will be the maximum tolerated dose. However, if at least 1 DLT is observed in the first 3 patients, 3 additional subjects will be enrolled at dose level 1. If more than 2 DLTs are observed in these 6 subjects, then dose de-escalation to 0.8 mg/m2 (dose level 0) will occur and 3-6 additional subjects may be enrolled.

All subjects in the phase II portion of the study will receive the maximum tolerated dose determined in the phase Ib portion.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Miltenyi CliniMACS Prodigy ® system

Subjects will receive an allogeneic stem cell transplant that has been depleted of ⍺/β T-cells and CD19+ B-cells using the Miltenyi CliniMACS Prodigy® system.

Intervention Type DEVICE

Zoledronic acid

All subjects will receive zoledronic acid intravenously on days +28, +56, +84, +112, and +140.

Dosing in the phase Ib portion of the study will follow a 3 + 3 design where the first 3 subjects will receive the expected phase II dose of 1.25 mg/m2 (dose level 1). If no dose-limiting toxicities (DLTs) occur in these subjects, dose level 1 will be the maximum tolerated dose. However, if at least 1 DLT is observed in the first 3 patients, 3 additional subjects will be enrolled at dose level 1. If more than 2 DLTs are observed in these 6 subjects, then dose de-escalation to 0.8 mg/m2 (dose level 0) will occur and 3-6 additional subjects may be enrolled.

All subjects in the phase II portion of the study will receive the maximum tolerated dose determined in the phase Ib portion.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients 6 months to ≤ 25 years old
* Relapsed/Refractory Solid Tumor whom failed or deemed ineligible to receive autologous transplant or if autologous transplant did not offer \>20% chance of cure with the following diseases:

1. neuroblastoma (high risk with relapsed or refractory disease),
2. relapsed/refractory rhabdomyosarcoma,
3. relapsed/refractory non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): synovial sarcoma, malignant peripheral nerve sheath tumors (MPNST),
4. High risk adult type NRSTS: clear cell sarcoma, alveolar soft part sarcoma,
5. Other high-risk extracranial solid tumors: desmoplastic small round cell tumors, chordoma, malignant rhabdoid tumor, epithelioid sarcoma, myoepithelial tumor
6. relapsed/refractory bone tumors: osteosarcoma and Ewing sarcoma/PNET, or
7. other high-risk solid tumors with \<10% expected survival with conventional treatment.
* Subjects must not have more than one active malignancy at the time of enrollment. (Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen \[as determined by the treating physician and approved by the PI\] may be included.)
* Haplo-identical related donor (at least one full haplotype must be matched).
* Karnofsky or Lansky score ≥60% at the time of enrollment. Karnofsky scores must be used for patients \>16 years of age and Lansky scores for patients ≤16 years of age
* Adequate organ function (within 4 weeks of initiation of preparative regimen), defined as:

1. Pulmonary: FEV1, FVC, and corrected DLCO must all be ≥ 50% of predicted by pulmonary function tests (PFTs). For children who are unable to perform for PFTs due to age, the criteria are: no evidence of dyspnea at rest and no need for supplemental oxygen.
2. Renal: Creatinine clearance or radioisotope GFR ≥60 mL/min/1.73 m2 or a serum creatinine based on age/gender
3. Cardiac: Ejection fraction of ≥ 40% by echocardiogram or radionuclide scan (MUGA).
* Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures
* Individuals of childbearing potential (IOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for one year following transplantation to minimize the risk of pregnancy. Prior to study enrollment, individuals of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factor for an unintentional pregnancy.
* Subjects with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for one year following stem cell transplantation.

* Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least one year after transplantation.
* Females who are known to be pregnant or breastfeeding.
* History of any other disease, metabolic dysfunction, clinical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.
* Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.

Exclusion Criteria

* Patients with documented uncontrolled infection at the time of study entry are not eligible.

a. Uncontrolled infection is patient without treatment antimicrobials and/or demonstrating progression despite antimicrobials
* Demonstrated lack of compliance with medical care, as determined by the treating physician.
* Patients who have received an allogeneic HSCT within 6 months.
* Patients who do not have an eligible allogeneic donor available.
* Patients with a life expectancy \<3 months
Minimum Eligible Age

6 Months

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Florida

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jordan Milner, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Florida

Gainesville, Florida, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Giselle Moore-Higgs, PhD, APRN

Role: CONTACT

352-273-9050

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Giselle Moore-Higgs, PhD, APRN

Role: primary

352-273-9050

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

IRB202500132

Identifier Type: OTHER

Identifier Source: secondary_id

UF-PED-006

Identifier Type: -

Identifier Source: org_study_id