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

NCT04530487 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2020-0496NCI-2020-05879
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Desmoplastic Small Round Cell Tumor; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Desmoplastic Small Round Cell Tumor; Recurrent Malignant Peripheral Nerve Sheath Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Rhabdomyosarcoma; Refractory Desmoplastic Small Round Cell Tumor; Refractory Malignant Peripheral Nerve Sheath Tumor; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Rhabdomyosarcoma

Outcome Measures

Primary Outcomes (2)

• Tolerability of Allogeneic HCT

  To assess tolerability of allogeneic HCT for patients with chemo-responsive recurrent/refractory solid tumors as defined by transplant-related mortality (TRM) at day 30

  By day +30 after allogeneic HCT infusion

• Rate of Organ Toxicity

  The rate of grade III or higher organ toxicity (Bearman Regimen-Related Toxicities Scale)\[1\] attributable to conditioning occurring within 30 days.

  By day +30 after allogeneic HCT infusion

Study Arms (1)

Treatment (conditioning regimen, HSCT)

EXPERIMENTAL

CONDITIONING REGIMEN: Patients receive thiotepa IV over 2-4 hours, 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 -3 and -4. TRANSPLANT: Patients undergo HSCT on day 0. GVHD PROPHYLAXIS: Beginning day -2, patients receive tacrolimus or cyclosporine IV continuously until able to receive 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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclosporine; Drug: Etoposide; Drug: Fludarabine Phosphate; Biological: Lapine T-Lymphocyte Immune Globulin; Drug: Melphalan; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Drug: Thiotepa

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo HSCT

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (conditioning regimen, HSCT)

Cyclosporine DRUG

Given IV and PO

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Cyclosporine Modified, Gengraf, Neoral, OL 27-400, Sandimmune, SangCya

Treatment (conditioning regimen, HSCT)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16

Treatment (conditioning regimen, HSCT)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (conditioning regimen, HSCT)

Lapine T-Lymphocyte Immune Globulin BIOLOGICAL

Given IV

Also known as: Anti-Thymocyte Globulin Rabbit, Grafalon, Rabbit Anti-Human Thymocyte Globulin (RATG), Rabbit Anti-Thymocyte Globulin, Rabbit Antithymocyte Globulin, Rabbit ATG, rATG, Thymoglobulin

Treatment (conditioning regimen, HSCT)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (conditioning regimen, HSCT)

Mycophenolate Mofetil DRUG

Given IV or PO

Also known as: CellCept, MMF

Treatment (conditioning regimen, HSCT)

Tacrolimus DRUG

Given IV and PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (conditioning regimen, HSCT)

Thiotepa DRUG

Given IV

Also known as: 1,1'',1''''-Phosphinothioylidynetrisaziridine, Girostan, N,N'', N''''-Triethylenethiophosphoramide, Oncotiotepa, STEPA, Tepadina, TESPA, Tespamin, Tespamine, Thio-Tepa, Thiofosfamide, Thiofozil, Thiophosphamide, Thiophosphoramide, Thiotef, Tifosyl, TIO TEF, Tio-tef, Triethylene Thiophosphoramide, Triethylenethiophosphoramide, Tris(1-aziridinyl)phosphine sulfide, TSPA, WR 45312

Treatment (conditioning regimen, HSCT)

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Desmoplastic Small Round Cell Tumor; Neuroectodermal Tumors, Primitive, Peripheral; Neurofibrosarcoma; Neuroblastoma; Rhabdomyosarcoma

Interventions

Stem Cell Transplantation; Cyclosporine; Cyclosporins; Etoposide; fludarabine phosphate; Antilymphocyte Serum; thymoglobulin; Melphalan; Mycophenolic Acid; Tacrolimus; Thiotepa

Condition Hierarchy (Ancestors)

Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neurofibroma; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Myosarcoma; Neoplasms, Muscle Tissue

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Glucosides; Glycosides; Carbohydrates; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Jeremy S Connors, MD
• Organization: M D Anderson Cancer Center

jsconnors@mdanderson.org

(713) 792-6624

Study Officials

• Jeremy S Connors, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2020
• First Posted: August 28, 2020
• Study Start: August 19, 2020
• Primary Completion: August 26, 2024
• Study Completion: August 26, 2024
• Last Updated: June 29, 2025
• Results First Posted: June 29, 2025

Record last verified: 2025-06

Locations

US (1)