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

NCT04521946 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 2020-0495NCI-2020-05878
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

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

Outcome Measures

Primary Outcomes (2)

• Transplant-related mortality

  Will be reported together with the corresponding 95% Bayesian credible interval. Will be estimated using the method of Gooley.

  At day 30

• Rate of grade III or higher organ toxicity attributable to conditioning

  Assessed per Bearman Regimen-Related Toxicities Scale. Will be reported together with the corresponding 95% Bayesian credible interval.

  Within 30 days

Secondary Outcomes (10)

• Failure of platelet and neutrophil engraftment rates

  Day 100

• Incidence of acute graft-versus-host (GVHD) disease

  Up to day 100

• Incidence of chronic GVHD

  At day 100 and 1 year

• Rate of grade II organ toxicity

  Up to day 100

• Rate of graft failure (primary and secondary)

  Up to day 100

Study Arms (1)

Treatment (chemotherapy, HCT)

EXPERIMENTAL

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.

Drug: Etoposide; Drug: Fludarabine Phosphate; Procedure: Hematopoietic Cell Transplantation; Biological: Lapine T-Lymphocyte Immune Globulin; Drug: Melphalan; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Drug: Thiotepa

Interventions

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16

Treatment (chemotherapy, HCT)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (chemotherapy, HCT)

Hematopoietic Cell Transplantation PROCEDURE

Undergo HCT

Also known as: HCT, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant, stem cell transplantation

Treatment (chemotherapy, HCT)

Lapine T-Lymphocyte Immune Globulin BIOLOGICAL

Given IV

Also known as: Anti-Thymocyte Globulin Rabbit, Grafalon, Rabbit Anti-Human Thymocyte Globulin (RATG), Rabbit Anti-Thymocyte Globulin, Rabbit Antithymocyte Globulin, Rabbit ATG, rATG, Thymoglobulin

Treatment (chemotherapy, HCT)

Melphalan DRUG

Given IV

Also known as: 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

Treatment (chemotherapy, HCT)

Mycophenolate Mofetil DRUG

Given PO or IV

Also known as: CellCept, MMF

Treatment (chemotherapy, HCT)

Tacrolimus DRUG

Given IV

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (chemotherapy, HCT)

Thiotepa DRUG

Given IV

Also known as: 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

Treatment (chemotherapy, HCT)

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Ependymoma; Rhabdoid Tumor; Choroid Plexus Carcinoma; Brain Neoplasms; Glioma; Medulloblastoma; Neuroectodermal Tumors, Primitive

Interventions

Etoposide; fludarabine phosphate; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Antilymphocyte Serum; thymoglobulin; Melphalan; Mycophenolic Acid; Tacrolimus; Thiotepa

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kris M Mahadeo, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: August 21, 2020
• Study Start: January 14, 2021
• Primary Completion: December 20, 2022
• Study Completion: December 20, 2022
• Last Updated: October 26, 2024

Record last verified: 2023-10