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

Primary Purpose

Desmoplastic Small Round Cell Tumor, Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Desmoplastic Small Round Cell Tumor

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Hematopoietic Stem Cell Transplantation
Cyclosporine
Etoposide
Fludarabine Phosphate
Lapine T-Lymphocyte Immune Globulin
Melphalan
Mycophenolate Mofetil
Tacrolimus
Thiotepa
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Desmoplastic Small Round Cell Tumor

Eligibility Criteria

undefined - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (conditioning regimen, HSCT)

Arm Description

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.

Outcomes

Primary Outcome Measures

Transplant-related mortality (TRM)
The proportion of patients with 30-day TRM will be reported together with the corresponding 95% Bayesian credible interval.
Rate of grade III or higher organ toxicity attributable to conditioning
Assessed using the Bearman Regimen-Related Toxicities Scale. The proportion of patients with 30-day grade III or higher organ toxicity will be reported together with the corresponding 95% Bayesian credible interval.

Secondary Outcome Measures

Time to platelet and neutrophil engraftment
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Incidence of acute graft versus host disease (aGVHD)
The 100-day rates of acute with the competing risk of relapse will be estimated using the method of Gooley.
Incidence of chronic GVHD
The 100-day rates of chronic GVHD with the competing risk of relapse will be estimated using the method of Gooley
Incidence of chronic GVHD
The 1 year rates of chronic GVHD with the competing risk of relapse will be estimated using the method of Gooley.
Rate of grade II organ toxicity
The 100-day rates of grade II organ toxicity will be reported as counts with percentages.
Rate of graft failure (primary and secondary)
The 100-day rates of primary and secondary graft failure will be reported as counts with percentages.
Rate of infectious complications
The 100-day rates of infectious complications will be reported as counts with percentages.
Progression-free survival (PFS)
Will be assessed using the method of Kaplan and Meier.
PFS
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
PFS
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Incidence of relapse
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Incidence of relapse
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Overall survival (OS)
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
OS
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.

Full Information

First Posted
August 25, 2020
Last Updated
October 5, 2023
Sponsor
M.D. Anderson Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT04530487
Brief Title
Donor Stem Cell Transplant After Chemotherapy for the Treatment of Recurrent or Refractory High-Risk Solid Tumors in Pediatric and Adolescent-Young Adults
Official Title
A Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric and Adolescent-Young Adults Patients With High Risk Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 19, 2020 (Actual)
Primary Completion Date
May 9, 2025 (Anticipated)
Study Completion Date
May 9, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (conditioning regimen, HSCT)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic
Intervention Description
Undergo HSCT
Intervention Type
Drug
Intervention Name(s)
Cyclosporine
Other Intervention Name(s)
27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Cyclosporine Modified, Gengraf, Neoral, OL 27-400, Sandimmune, SangCya
Intervention Description
Given IV and PO
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fludarabine Phosphate
Other Intervention Name(s)
2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Lapine T-Lymphocyte Immune Globulin
Other Intervention Name(s)
Anti-Thymocyte Globulin Rabbit, Grafalon, Rabbit Anti-Human Thymocyte Globulin (RATG), Rabbit Anti-Thymocyte Globulin, Rabbit Antithymocyte Globulin, Rabbit ATG, rATG, Thymoglobulin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
CellCept, MMF
Intervention Description
Given IV or PO
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
FK 506, Fujimycin, Hecoria, Prograf, Protopic
Intervention Description
Given IV and PO
Intervention Type
Drug
Intervention Name(s)
Thiotepa
Other Intervention Name(s)
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
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Transplant-related mortality (TRM)
Description
The proportion of patients with 30-day TRM will be reported together with the corresponding 95% Bayesian credible interval.
Time Frame
At 30 days
Title
Rate of grade III or higher organ toxicity attributable to conditioning
Description
Assessed using the Bearman Regimen-Related Toxicities Scale. The proportion of patients with 30-day grade III or higher organ toxicity will be reported together with the corresponding 95% Bayesian credible interval.
Time Frame
Up to 30 days
Secondary Outcome Measure Information:
Title
Time to platelet and neutrophil engraftment
Description
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Time Frame
Up to 1 year post transplant
Title
Incidence of acute graft versus host disease (aGVHD)
Description
The 100-day rates of acute with the competing risk of relapse will be estimated using the method of Gooley.
Time Frame
At 100 days post transplant
Title
Incidence of chronic GVHD
Description
The 100-day rates of chronic GVHD with the competing risk of relapse will be estimated using the method of Gooley
Time Frame
At 100 days post transplant
Title
Incidence of chronic GVHD
Description
The 1 year rates of chronic GVHD with the competing risk of relapse will be estimated using the method of Gooley.
Time Frame
At 1 year post transplant
Title
Rate of grade II organ toxicity
Description
The 100-day rates of grade II organ toxicity will be reported as counts with percentages.
Time Frame
Up to 100 days post transplant
Title
Rate of graft failure (primary and secondary)
Description
The 100-day rates of primary and secondary graft failure will be reported as counts with percentages.
Time Frame
Up to 100 days post transplant
Title
Rate of infectious complications
Description
The 100-day rates of infectious complications will be reported as counts with percentages.
Time Frame
Up to 100 days post transplant
Title
Progression-free survival (PFS)
Description
Will be assessed using the method of Kaplan and Meier.
Time Frame
At 180 days post transplant
Title
PFS
Description
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Time Frame
At 100 days post transplant
Title
PFS
Description
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Time Frame
At 1 year post transplant
Title
Incidence of relapse
Description
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Time Frame
At 100 days post transplant
Title
Incidence of relapse
Description
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Time Frame
At 1 year post transplant
Title
Overall survival (OS)
Description
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Time Frame
At 100 days post transplant
Title
OS
Description
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Time Frame
At 1 year post transplant

10. Eligibility

Sex
All
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dristhi Ragoonanan, MD
Phone
(713)792-6620
Email
dragoonanan@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dristhi Ragoonanan, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sajad Ragoonanan, MD
Phone
713-792-6620
Email
dragoonanan@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Sajad Ragoonanan, MD

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center

Learn more about this trial

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

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