Clinical Trials /

Chemotherapy and Donor Stem Transplant for the Treatment of Patients With High Grade Brain Cancer

NCT04521946

Description:

This phase I trial investigates the side effects and effectiveness of chemotherapy followed by a donor (allogeneic) stem cell transplant when given to patients with high grade brain cancer. 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:
  • Anaplastic Ependymoma
  • Atypical Teratoid/Rhabdoid Tumor
  • Brain Sarcoma
  • Central Nervous System Germ Cell Tumor
  • Choroid Plexus Carcinoma
  • Malignant Glioma
  • Medulloblastoma
  • Primitive Neuroectodermal Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Chemotherapy and Donor Stem Transplant for the Treatment of Patients With High Grade Brain Cancer
  • Official Title: A Pilot Study of Allogeneic Hematopoietic Cell Transplantation for Patients With High Grade Central Nervous System Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 2020-0495
  • SECONDARY ID: NCI-2020-05878
  • SECONDARY ID: 2020-0495
  • NCT ID: NCT04521946

Conditions

  • Anaplastic Ependymoma
  • Atypical Teratoid/Rhabdoid Tumor
  • Central Nervous System Germ Cell Tumor
  • Choroid Plexus Carcinoma
  • Intracranial Myeloid Sarcoma
  • Malignant Brain Neoplasm
  • Malignant Glioma
  • Medulloblastoma
  • Primitive Neuroectodermal Tumor
  • Recurrent Anaplastic Ependymoma
  • Recurrent Atypical Teratoid/Rhabdoid Tumor
  • Recurrent Malignant Brain Neoplasm
  • Recurrent Malignant Glioma
  • Recurrent Medulloblastoma
  • Recurrent Primitive Neuroectodermal Tumor

Interventions

DrugSynonymsArms
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16Treatment (chemotherapy, HCT)
Fludarabine Phosphate2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586Treatment (chemotherapy, HCT)
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 (chemotherapy, HCT)
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 (chemotherapy, HCT)
Mycophenolate MofetilCellCept, MMFTreatment (chemotherapy, HCT)
TacrolimusFK 506, Fujimycin, Hecoria, Prograf, ProtopicTreatment (chemotherapy, HCT)
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 (chemotherapy, HCT)

Purpose

This phase I trial investigates the side effects and effectiveness of chemotherapy followed by a donor (allogeneic) stem cell transplant when given to patients with high grade brain cancer. 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 allogenic hematopoietic cell transplantation (HCT) among
      patients with chemo-responsive high-grade central nervous system (CNS) malignancies as
      defined by transplant-related mortality (TRM) at day 30 as well as rate of grade III organ
      toxicity or higher (Bearman Regimen-Related Toxicities Scale) attributable to conditioning
      occurring within 30 days.

      SECONDARY OBJECTIVES:

      I. Median time to platelet and neutrophil engraftment. II. Incidence of acute
      graft-versus-host disease (aGVHD) by day 100. III. Incidence of chronic GVHD at day 100 and
      one year. IV. Rate of grade II organ toxicity through day 100. V. Rate of graft failure
      (primary and secondary) through day 100. VI. Rate of infectious complications through day
      100. VII. Progression free survival at day 180. VIII. Cumulative incidence of relapse,
      overall survival, and progression-free survival at 100 days and 1 year.

      OUTLINE:

      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. Patients receiving umbilical cord transplant only also
      receive lapine T-lymphocyte immune globulin IV over 4-12 hours on days -4 and -3. Patients
      then undergo HCT on day 0. Patients also receive tacrolimus IV or cyclosporine IV beginning
      on day -2 to and mycophenolate mofetil orally (PO) every 8 hours or IV from days 0-40 and
      tapered to day 90.

      After completion of study treatment, patients are followed up at 100, 180, 270 and 360 days.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (chemotherapy, HCT)ExperimentalPatients receive thiotepa 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. Patients receiving umbilical cord transplant only also receive lapine T-lymphocyte immune globulin IV over 4-12 hours on days -4 and -3. Patients then undergo HCT on day 0. Patients also receive tacrolimus IV or cyclosporine IV beginning on day -2 to and mycophenolate mofetil PO every 8 hours or IV from days 0-40 and tapered to day 90.
  • Etoposide
  • Fludarabine Phosphate
  • Lapine T-Lymphocyte Immune Globulin
  • Melphalan
  • Mycophenolate Mofetil
  • Tacrolimus
  • Thiotepa

Eligibility Criteria

        Inclusion Criteria:

          -  Pathological criteria for any high grade primary or recurrent malignant brain tumor -
             medulloblastoma (patients who are ineligible for tandem autologous transplants or who
             are at least 3 months post autologous HCT), primitive neuroectodermal tumor (PNET),
             atypical teratoid rhabdoid tumor (ATRT), malignant glioma, CNS germ cell tumor,
             intracranial sarcomas, choroid plexus carcinoma, anaplastic ependymoma. High grade
             tumors defined as those that are grade III or higher based on World Health
             Organization (WHO) classification grading system or for medulloblastoma: group 3 and 4
             molecular subtypes

          -  Patients have to be in at least, a chemo-responsive disease status

          -  Available suitable HCT donor

          -  Creatinine clearance or glomerular filtration rate (GFR) >= 50 ml/min/1.73m^2, and not
             requiring dialysis

          -  Diffusion capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin)
             >= 50% predicted. If unable to perform pulmonary function tests, then O2 saturation >=
             92% in room air

          -  Bilirubin =< 3x upper limit of normal (ULN) (with the exception of isolated
             hyperbilirubinemia due to Gilbert's syndrome)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5x for age

          -  DONOR: HCT will be done using stem cell sources in the following order of preference
             (and fulfilling minimal cell dose requirements per institutional standards):

               -  Matched related donor bone marrow (10 of 10 human leukocyte antigen [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 guardian/donor

               -  Matched allogeneic umbilical cord blood: related

                    -  High-resolution matching at A,B, DRB1 (minimum 4/6)

                    -  Killer-cell immunoglobulin-like receptor (KIR) major histocompatibility
                       complex (MHC) class 1 preferential mismatch (minimum 4/6)

               -  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 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

          -  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 inclusion criteria listed above
      
Maximum Eligible Age:25 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Transplant-related mortality
Time Frame:At day 30
Safety Issue:
Description:Will be reported together with the corresponding 95% Bayesian credible interval. Will be estimated using the method of Gooley.

Secondary Outcome Measures

Measure:Failure of platelet and neutrophil engraftment rates
Time Frame:Day 100
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 (GVHD) disease
Time Frame:Up to day 100
Safety Issue:
Description:Will be estimated using the method of Gooley.
Measure:Incidence of chronic GVHD
Time Frame:At day 100 and 1 year
Safety Issue:
Description:Will be estimated using the method of Gooley.
Measure:Rate of grade II organ toxicity
Time Frame:Up to day 100
Safety Issue:
Description:Will be reported as counts with percentages.
Measure:Rate of graft failure (primary and secondary)
Time Frame:Up to day 100
Safety Issue:
Description:Will be reported as counts with percentages.
Measure:Rate of infectious complications
Time Frame:Up to day 100
Safety Issue:
Description:Will be reported as counts with percentages.
Measure:Progression free survival
Time Frame:At day 180
Safety Issue:
Description:
Measure:Cumulative incidence of relapse
Time Frame:At day 100 and 1 year
Safety Issue:
Description:Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Measure:Overall survival
Time Frame:At day 100 and 1 year
Safety Issue:
Description:Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Measure:Progression-free survival
Time Frame:At day 100 and 1 year
Safety Issue:
Description:Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

August 18, 2020