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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

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ClinicalTrials.gov Identifier: NCT04530487
Recruitment Status : Recruiting
First Posted : August 28, 2020
Last Update Posted : February 21, 2021
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
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 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 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric and Adolescent-Young Adults Patients With High Risk Solid Tumors
Actual Study Start Date : August 19, 2020
Estimated Primary Completion Date : May 9, 2025
Estimated Study Completion Date : May 9, 2025


Arm Intervention/treatment
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
Undergo HSCT
Other Names:
  • Allogeneic Hematopoietic Cell Transplantation
  • Allogeneic Stem Cell Transplantation
  • HSC
  • HSCT
  • Stem Cell Transplantation, Allogeneic

Drug: Cyclosporine
Given IV and PO
Other Names:
  • 27-400
  • Ciclosporin
  • CsA
  • Cyclosporin
  • Cyclosporin A
  • Cyclosporine Modified
  • Gengraf
  • Neoral
  • OL 27-400
  • Sandimmune
  • SangCya

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16
  • VP 16-213
  • VP-16
  • VP-16-213
  • VP16

Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586

Biological: Lapine T-Lymphocyte Immune Globulin
Given IV
Other Names:
  • Anti-Thymocyte Globulin Rabbit
  • Grafalon
  • Rabbit Anti-Human Thymocyte Globulin (RATG)
  • Rabbit Anti-Thymocyte Globulin
  • Rabbit Antithymocyte Globulin
  • Rabbit ATG
  • rATG
  • Thymoglobulin

Drug: Melphalan
Given IV
Other Names:
  • 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

Drug: Mycophenolate Mofetil
Given IV or PO
Other Names:
  • CellCept
  • MMF

Drug: Tacrolimus
Given IV and PO
Other Names:
  • FK 506
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic

Drug: Thiotepa
Given IV
Other Names:
  • 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




Primary Outcome Measures :
  1. Transplant-related mortality (TRM) [ Time Frame: At 30 days ]
    The proportion of patients with 30-day TRM will be reported together with the corresponding 95% Bayesian credible interval.

  2. Rate of grade III or higher organ toxicity attributable to conditioning [ Time Frame: Up to 30 days ]
    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 :
  1. Time to platelet and neutrophil engraftment [ Time Frame: Up to 1 year post transplant ]
    Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.

  2. Incidence of acute graft versus host disease (aGVHD) [ Time Frame: At 100 days post transplant ]
    The 100-day rates of acute with the competing risk of relapse will be estimated using the method of Gooley.

  3. Incidence of chronic GVHD [ Time Frame: At 100 days post transplant ]
    The 100-day rates of chronic GVHD with the competing risk of relapse will be estimated using the method of Gooley

  4. Incidence of chronic GVHD [ Time Frame: At 1 year post transplant ]
    The 1 year rates of chronic GVHD with the competing risk of relapse will be estimated using the method of Gooley.

  5. Rate of grade II organ toxicity [ Time Frame: Up to 100 days post transplant ]
    The 100-day rates of grade II organ toxicity will be reported as counts with percentages.

  6. Rate of graft failure (primary and secondary) [ Time Frame: Up to 100 days post transplant ]
    The 100-day rates of primary and secondary graft failure will be reported as counts with percentages.

  7. Rate of infectious complications [ Time Frame: Up to 100 days post transplant ]
    The 100-day rates of infectious complications will be reported as counts with percentages.

  8. Progression-free survival (PFS) [ Time Frame: At 180 days post transplant ]
    Will be assessed using the method of Kaplan and Meier.

  9. PFS [ Time Frame: At 100 days post transplant ]
    Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.

  10. PFS [ Time Frame: At 1 year post transplant ]
    Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.

  11. Incidence of relapse [ Time Frame: At 100 days post transplant ]
    Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.

  12. Incidence of relapse [ Time Frame: At 1 year post transplant ]
    Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.

  13. Overall survival (OS) [ Time Frame: At 100 days post transplant ]
    Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.

  14. OS [ Time Frame: At 1 year post transplant ]
    Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04530487


Contacts
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Contact: Kris M Mahadeo 713-792-6610 kmmahadeo@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Kris M. Mahadeo    713-792-6610      
Principal Investigator: Kris M. Mahadeo         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
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Principal Investigator: Kris M Mahadeo M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT04530487    
Other Study ID Numbers: 2020-0496
NCI-2020-05879 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2020-0496 ( Other Identifier: M D Anderson Cancer Center )
First Posted: August 28, 2020    Key Record Dates
Last Update Posted: February 21, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Neuroblastoma
Rhabdomyosarcoma
Sarcoma, Ewing
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Nerve Sheath Neoplasms
Neurofibrosarcoma
Desmoplastic Small Round Cell Tumor
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Myosarcoma
Neoplasms, Muscle Tissue
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Fibrosarcoma
Neoplasms, Fibrous Tissue
Neurofibroma