Alpha/beta T‑Cell and B‑Cell Depletion plus Zoledronic Acid for Pediatric and Young Adult Solid Tumors

Allogeneic Stem Cell Transplantation Utilizing Alpha/Beta T Cell and CD19+ B Cell Depletion With Zoledronic Acid in Combination to Treat Pediatric, Adolescent, and Young Adult Patients With Relapsed/Refractory Solid Tumors

This study will try removing alpha/beta T cells and B cells from donor stem cell grafts and giving zoledronic acid to see if it helps children and young adults (6 months to 25 years) with relapsed or high‑risk solid tumors tolerate allogeneic transplant and reduce relapse.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 6 Months to 25 Years
• Sex: All
• Sponsor: University of Florida (other)
• Drugs / interventions: chemotherapy, Immunotherapy
• Locations: 1 site (Gainesville, Florida)
• Trial ID: NCT06625190 on ClinicalTrials.gov

What this trial studies

Patients will receive allogeneic hematopoietic stem cell transplants after ex vivo depletion of alpha/beta T cells and B cells using the Miltenyi CliniMACS Prodigy system, with zoledronic acid given around the time of transplant. The protocol aims to reduce graft‑versus‑host disease (GVHD) and post‑transplant lymphoproliferative disease (PTLD) while preserving or enhancing graft‑versus‑tumor effects against relapsed or refractory pediatric and young adult solid tumors. The trial enrolls patients aged 6 months to ≤25 years with a variety of high‑risk extracranial solid tumors who have failed or are not candidates for autologous transplant, and uses a Phase 1/2 safety and early efficacy design. All procedures and follow‑up are conducted at a single center.

Who should consider this trial

Good fit: Ideal candidates are patients 6 months to ≤25 years with relapsed/refractory or high‑risk extracranial solid tumors who failed or are ineligible for autologous transplant and are medically fit for allogeneic stem cell transplantation.

Not a fit: Patients who have good expected survival with standard therapy, who have multiple uncontrolled active malignancies, severe organ dysfunction, or uncontrolled infection are unlikely to benefit from this transplant approach.

Why it matters

Potential benefit: If successful, this approach could expand donor options, lower rates of severe GVHD and PTLD, and improve disease control after allogeneic transplant for high‑risk pediatric and young adult solid tumors.

How similar studies have performed: Alpha/beta T‑cell and B‑cell depletion has reduced GVHD and enabled haploidentical transplants in hematologic diseases, but evidence for meaningful graft‑versus‑tumor benefit in solid tumors is limited and not yet established.

Eligibility criteria

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.

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
* Patients not meeting inclusion criteria for organ function.
* 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.

Where this trial is running

Gainesville, Florida

• University of Florida — Gainesville, Florida, United States (RECRUITING)

Study contacts

• Principal investigator: Jordan Milner, MD — University of Florida
• Study coordinator: Giselle Moore-Higgs, PhD, APRN

Conditions: Neuroblastoma, Rhabdomyosarcoma, Synovial Sarcoma, Peripheral Nerve Sheath Tumors, Clear Cell Sarcoma, Alveolar Soft Part Sarcoma, Desmoplastic Small Round Cell Tumor, Chordoma