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

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ClinicalTrials.gov Identifier: NCT04521946
Recruitment Status : Recruiting
First Posted : August 21, 2020
Last Update Posted : February 21, 2021
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE August 18, 2020
First Posted Date  ICMJE August 21, 2020
Last Update Posted Date February 21, 2021
Actual Study Start Date  ICMJE January 14, 2021
Estimated Primary Completion Date May 9, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2020)
  • Transplant-related mortality [ Time Frame: At day 30 ]
    Will be reported together with the corresponding 95% Bayesian credible interval. Will be estimated using the method of Gooley.
  • Rate of grade III or higher organ toxicity attributable to conditioning [ Time Frame: Within 30 days ]
    Assessed per Bearman Regimen-Related Toxicities Scale. Will be reported together with the corresponding 95% Bayesian credible interval.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2020)
  • Failure of platelet and neutrophil engraftment rates [ Time Frame: Day 100 ]
    Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
  • Incidence of acute graft-versus-host (GVHD) disease [ Time Frame: Up to day 100 ]
    Will be estimated using the method of Gooley.
  • Incidence of chronic GVHD [ Time Frame: At day 100 and 1 year ]
    Will be estimated using the method of Gooley.
  • Rate of grade II organ toxicity [ Time Frame: Up to day 100 ]
    Will be reported as counts with percentages.
  • Rate of graft failure (primary and secondary) [ Time Frame: Up to day 100 ]
    Will be reported as counts with percentages.
  • Rate of infectious complications [ Time Frame: Up to day 100 ]
    Will be reported as counts with percentages.
  • Progression free survival [ Time Frame: At day 180 ]
  • Cumulative incidence of relapse [ Time Frame: At day 100 and 1 year ]
    Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
  • Overall survival [ Time Frame: At day 100 and 1 year ]
    Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
  • Progression-free survival [ Time Frame: At day 100 and 1 year ]
    Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chemotherapy and Donor Stem Transplant for the Treatment of Patients With High Grade Brain Cancer
Official Title  ICMJE A Pilot Study of Allogeneic Hematopoietic Cell Transplantation for Patients With High Grade Central Nervous System Malignancies
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
  • Procedure: Hematopoietic Cell Transplantation
    Undergo HCT
    Other Names:
    • HCT
    • Hematopoietic Stem Cell Transplantation
    • HSCT
    • Stem Cell Transplant
    • stem cell transplantation
  • 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 PO or IV
    Other Names:
    • CellCept
    • MMF
  • Drug: Tacrolimus
    Given IV
    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
Study Arms  ICMJE Experimental: Treatment (chemotherapy, HCT)
Patients 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.
Interventions:
  • Drug: Etoposide
  • Drug: Fludarabine Phosphate
  • Procedure: Hematopoietic Cell Transplantation
  • Biological: Lapine T-Lymphocyte Immune Globulin
  • Drug: Melphalan
  • Drug: Mycophenolate Mofetil
  • Drug: Tacrolimus
  • Drug: Thiotepa
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 18, 2020)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 9, 2025
Estimated Primary Completion Date May 9, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04521946
Other Study ID Numbers  ICMJE 2020-0495
NCI-2020-05878 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2020-0495 ( Other Identifier: M D Anderson Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kris M Mahadeo M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP