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TerminatedNCT04530487Updated Jun 29, 2025Results posted

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

A Phase 2 interventional study of Allogeneic Hematopoietic Stem Cell Transplantation and Cyclosporine in Desmoplastic Small Round Cell Tumor, Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor and Recurrent Desmoplastic Small Round Cell Tumor, sponsored by M.D. Anderson Cancer Center. Terminated at 1 site in United States. Open to participants aged Up to 25 Years. Per ClinicalTrials.gov, last updated 2025-06-29.

Sponsored by M.D. Anderson Cancer Center · Phase 2, Interventional, and Treatment

Why this study was terminated
PI Request
Phase
Phase 2
Study type
Interventional
Enrollment
1
Allocation
Not applicable
Ages
Up to 25 Years
Sex
All
01

Study 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.

Read the detailed description

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.

After completion of HSCT, patients are followed up for up to 1 year.

02

Conditions studied

  • 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
03

Who can participate

Ages eligible
Up to 25 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
1 participant (actual)

Study arms

  • Experimental
    Treatment (conditioning regimen, HSCT)

    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

  • ProcedureAllogeneic Hematopoietic Stem Cell Transplantation

    Undergo HSCT

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

  • DrugCyclosporine

    Given IV and PO

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

  • DrugEtoposide

    Given IV

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

  • DrugFludarabine Phosphate

    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

  • BiologicalLapine T-Lymphocyte Immune Globulin

    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

  • DrugMelphalan

    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

  • DrugMycophenolate Mofetil

    Given IV or PO

    Also known as: CellCept, MMF

  • DrugTacrolimus

    Given IV and PO

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

  • DrugThiotepa

    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

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: By day +30 after allogeneic HCT infusion

  2. 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.

    Time frame: By day +30 after allogeneic HCT infusion

06

Results

Posted Jun 29, 2025

Participant flow

This study was open to accrual from 8/19/2020 to 7/23/2024. Participants were referred for the study both internally and externally.

Participant flow — Overall Study
MilestoneAllogeneic Stem Cell Transplant in High Risk Solid Tumors
Started1
Completed0
Not completed1
Withdrew: Death1

Outcome measures

PrimaryTolerability 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

Time frame:
By day +30 after allogeneic HCT infusion

No measurements were reported for this outcome.

PrimaryRate 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.

Time frame:
By day +30 after allogeneic HCT infusion

No measurements were reported for this outcome.

Adverse events

Collected over From the start of preparative regimen up to D+100 the collection of adverse events will reflect the onset and resolution date and maximum grade. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Allogeneic Stem Cell Transplant in High Risk Solid Tumors1/1 (100%)0/1 (0%)1/1 (100%)
Most frequent other events
Showing 10 of 23
Most frequent other events
EventAllogeneic Stem Cell Transplant in High Risk Solid Tumors
Alanine aminotransferase increasedInvestigations1/1
AnorexiaMetabolism and nutrition disorders1/1
Aspartate aminotransferase increasedInvestigations1/1
Blood lactate dehydrogenase increasedInvestigations1/1
Creatinine IncreaseInvestigations1/1
DiarrheaGastrointestinal disorders1/1
FatigueGeneral disorders1/1
FeverGeneral disorders1/1
Generalized EdemaGeneral disorders1/1
HypertensionVascular disorders1/1

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Allogeneic Stem Cell Transplant in High Risk Solid Tumors
<=18 years1
Between 18 and 65 years0
>=65 years0
Age, Continuous
Age, Continuous(years)Allogeneic Stem Cell Transplant in High Risk Solid Tumors
Mean12 (12 to 12)
Sex: Female, Male
Sex: Female, Male(Participants)Allogeneic Stem Cell Transplant in High Risk Solid Tumors
Female0
Male1
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Allogeneic Stem Cell Transplant in High Risk Solid Tumors
Hispanic or Latino0
Not Hispanic or Latino1
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Allogeneic Stem Cell Transplant in High Risk Solid Tumors
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White1
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Allogeneic Stem Cell Transplant in High Risk Solid Tumors
United States1
07

Study locations

1 site
  • M D Anderson Cancer Center
    Houston, Texas 77030, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Mar 18, 2024
  • Informed consent form · Mar 18, 2024

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT04530487
Lead sponsor
M.D. Anderson Cancer Center
Responsible party
Sponsor
First posted
Aug 28, 2020
Start date
Aug 19, 2020
Primary completion
Aug 26, 2024
Completion
Aug 26, 2024
Results posted
Jun 29, 2025
Last update
Jun 29, 2025

Study contacts

Jeremy S Connors, MD
principal investigator · M.D. Anderson Cancer Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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