This phase II trial investigates side effects and how well donor stem cell transplant after chemotherapy works in treating pediatric and adolescent-young adults with high-risk solid tumor that has come back (recurrent) or does not respond to treatment (refractory). Chemotherapy drugs, such as fludarabine, thiotepa, etoposide, melphalan, and rabbit anti-thymocyte globulin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a donor stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04530487.
PRIMARY OBJECTIVE:
I. To assess tolerability of allogeneic hematopoietic stem cell transplantation (HCT) for patients with chemo-responsive recurrent/refractory solid tumors as defined by transplant-related mortality (TRM) at day 30 and the rate of grade III or higher organ toxicity (Bearman Regimen-Related Toxicities Scale) attributable to conditioning occurring within 30 days.
SECONDARY OBJECTIVES:
I. Assess median time to platelet and neutrophil engraftment.
II. Assess incidence of acute graft-versus-host disease (aGVHD) by day 100.
III. Assess incidence of chronic GVHD (cGVHD) at day 100 and one year.
IV. Assess rate of grade II organ toxicity through day 100.
V. Assess rate of graft failure (primary and secondary) through day 100.
VI. Assess rate of infectious complications through day 100.
VII. Assess progression free survival (PFS) at day 100,180 and 365.
VIII. Assess cumulative incidence of relapse, overall survival (OS) at 100 days and 1 year.
OUTLINE:
CONDITIONING REGIMEN: Patients receive thiotepa intravenously (IV) over 2-4 hours and etoposide IV over 60 minutes on days -8 to -6, melphalan IV over 20 minutes on days -5 and -4, and fludarabine phosphate IV over 1 hour on days -5 to -3 in the absence of disease progression or unacceptable toxicity. Patients receiving umbilical cord transplant also receive rabbit anti-thymocyte globulin IV on days -4 and -3.
TRANSPLANT: Patients undergo HSCT on day 0.
GVHD PROPHYLAXIS: Beginning day -2, patients receive tacrolimus or cyclosporine IV continuously until able to receive orally (PO). Patients continue tacrolimus or cyclosporine PO to day 60 and tapered to day 100. Patients also receive mycophenolate mofetil PO or IV every 8 hours until day 40 and tapered to day 90.
Patients undergo echocardiography, magnetic resonance imaging (MRI) or multigated acquisition (MUGA) scan, computed tomography (CT) scan, bone marrow aspiration and biopsy, and blood sample collection throughout the study.
After completion of HSCT, patients are followed up for up to 1 year.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorJeremy Scott Connors
