Donor Stem Cell Transplant After Chemotherapy for the Treatment of Recurrent or Refractory High-Risk Solid Tumors in Pediatric and Adolescent-Young Adults

• Status: Recruiting
• Trial end date: 2025-05-09
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Antibodies; Antilymphocyte Serum; Cyclosporine; Cyclosporins; Etoposide; Etoposide phosphate; Fludarabine; Fludarabine phosphate; gamma-Globulins; Immunoglobulins; Immunoglobulins, Intravenous; Mechlorethamine; Melphalan; Mycophenolic Acid; Nitrogen Mustard Compounds; Podophyllotoxin; Rho(D) Immune Globulin; Tacrolimus; Thiotepa; Thymoglobulin

Criteria

Inclusion Criteria:

• Pathological criteria, including malignant recurrent/refractory solid tumors. This would include:

• Ewing's/peripheral primitive neuroectodermal tumor (PNET)

• Malignant peripheral nerve sheath tumor, neurofibrosarcoma

• Rhabdomyosarcoma

• Neuroblastoma (patients who are ineligible for tandem autologous transplant or who are at least 3 months post autologous HCT)

• Desmoplastic small round cell tumor (DSRCT)- both new diagnoses as well as recurrent/refractory disease

• Patients must have chemo-responsive disease, defined as; 30% or greater decrease in the tumor target lesions when compared to its pre-treatment evaluation. Patients with complete response will be eligible to participate

• Available suitable HCT donor

• Creatinine clearance or glomerular filtration rate (GFR) >= 50 ml/min/1.73m^2, and not requiring dialysis

• Diffusing capacity of lung for carbon monoxide (DLCO) (corrected for hemoglobin) >= 50% predicted. If unable to perform pulmonary function tests, then oxygen (O2) saturation >= 92% in room air

• Bilirubin =< 3 x upper limit of normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 x for age (with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome)

• DONOR: Matched related donor bone marrow (10 of 10 HLA alleles [HLA-A, B, C, DR, and DQ]. Matched related donor peripheral blood stem cell (PBSC) is allowed only if collection of bone marrow (BM) is not available or refused by parents/donor

• DONOR: Matched allogeneic umbilical cord blood (UCB): related

• High-resolution matching at A,B, DRB1 (minimum 4/6)

• KIR major histocompatibility complex (MHC) class 1 preferential mismatch (minimum 4/6)

• DONOR: Matched allogeneic umbilical cord blood: unrelated

• High-resolution matching at A,B, DRB1 (minimum 4/6) •*KIR MHC class 1 preferential mismatch (minimum 4/6)

Exclusion Criteria:

• Lack of histocompatible suitable related donor/ graft source

• End-organ failure that precludes the ability to tolerate the transplant procedure, including conditioning regimen

• Renal failure requiring dialysis

• Congenital heart disease resulting in congestive heart failure

• Ventilatory failure: requires invasive mechanical ventilation

• Human immunodeficiency virus (HIV) infection

• Uncontrolled bacterial, viral, or fungal infections (currently taking medication yet clinical symptoms progress); stable, controlled disease with treatment is not an exclusion criteria

• A female of reproductive potential who is pregnant, planning to become pregnant during the study, or is nursing a child

• Any patient who does not fulfill the inclusion criteria listed above