Clinical Trials /

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

NCT04530487

Description:

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.

Related Conditions:
  • Desmoplastic Small Round Cell Tumor
  • Malignant Peripheral Nerve Sheath Tumor
  • Neuroblastoma
  • Peripheral Primitive Neuroectodermal Tumor
  • Rhabdomyosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2020-0496
  • SECONDARY ID: NCI-2020-05879
  • SECONDARY ID: 2020-0496
  • NCT ID: NCT04530487

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

Interventions

DrugSynonymsArms
Cyclosporine27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Cyclosporine Modified, Gengraf, Neoral, OL 27-400, Sandimmune, SangCyaTreatment (conditioning regimen, HSCT)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16Treatment (conditioning regimen, HSCT)
Fludarabine Phosphate2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586Treatment (conditioning regimen, HSCT)
Lapine T-Lymphocyte Immune GlobulinAnti-Thymocyte Globulin Rabbit, Grafalon, Rabbit Anti-Human Thymocyte Globulin (RATG), Rabbit Anti-Thymocyte Globulin, Rabbit Antithymocyte Globulin, Rabbit ATG, rATG, ThymoglobulinTreatment (conditioning regimen, HSCT)
MelphalanAlanine 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-19813Treatment (conditioning regimen, HSCT)
Mycophenolate MofetilCellCept, MMFTreatment (conditioning regimen, HSCT)
TacrolimusFK 506, Fujimycin, Hecoria, Prograf, ProtopicTreatment (conditioning regimen, HSCT)
Thiotepa1,1'',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 45312Treatment (conditioning regimen, HSCT)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (conditioning regimen, HSCT)ExperimentalCONDITIONING 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.
  • Cyclosporine
  • Etoposide
  • Fludarabine Phosphate
  • Lapine T-Lymphocyte Immune Globulin
  • Melphalan
  • Mycophenolate Mofetil
  • Tacrolimus
  • Thiotepa

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
      
Maximum Eligible Age:25 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Transplant-related mortality (TRM)
Time Frame:At 30 days
Safety Issue:
Description:The proportion of patients with 30-day TRM will be reported together with the corresponding 95% Bayesian credible interval.

Secondary Outcome Measures

Measure:Time to platelet and neutrophil engraftment
Time Frame:Up to 1 year post transplant
Safety Issue:
Description:Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Measure:Incidence of acute graft versus host disease (aGVHD)
Time Frame:At 100 days post transplant
Safety Issue:
Description:The 100-day rates of acute with the competing risk of relapse will be estimated using the method of Gooley.
Measure:Incidence of chronic GVHD
Time Frame:At 100 days post transplant
Safety Issue:
Description:The 100-day rates of chronic GVHD with the competing risk of relapse will be estimated using the method of Gooley
Measure:Incidence of chronic GVHD
Time Frame:At 1 year post transplant
Safety Issue:
Description:The 1 year rates of chronic GVHD with the competing risk of relapse will be estimated using the method of Gooley.
Measure:Rate of grade II organ toxicity
Time Frame:Up to 100 days post transplant
Safety Issue:
Description:The 100-day rates of grade II organ toxicity will be reported as counts with percentages.
Measure:Rate of graft failure (primary and secondary)
Time Frame:Up to 100 days post transplant
Safety Issue:
Description:The 100-day rates of primary and secondary graft failure will be reported as counts with percentages.
Measure:Rate of infectious complications
Time Frame:Up to 100 days post transplant
Safety Issue:
Description:The 100-day rates of infectious complications will be reported as counts with percentages.
Measure:Progression-free survival (PFS)
Time Frame:At 180 days post transplant
Safety Issue:
Description:Will be assessed using the method of Kaplan and Meier.
Measure:PFS
Time Frame:At 100 days post transplant
Safety Issue:
Description:Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Measure:PFS
Time Frame:At 1 year post transplant
Safety Issue:
Description:Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Measure:Incidence of relapse
Time Frame:At 100 days post transplant
Safety Issue:
Description:Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Measure:Incidence of relapse
Time Frame:At 1 year post transplant
Safety Issue:
Description:Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Measure:Overall survival (OS)
Time Frame:At 100 days post transplant
Safety Issue:
Description:Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Measure:OS
Time Frame:At 1 year post transplant
Safety Issue:
Description:Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

August 25, 2020