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

NCT ID: NCT04521946

Last Updated: 2024-10-26

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-14
• Study Completion Date: 2022-12-20

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Etoposide

Intervention Type: DRUG

Given IV

Fludarabine Phosphate

Intervention Type: DRUG

Given IV

Hematopoietic Cell Transplantation

Intervention Type: PROCEDURE

Undergo HCT

Lapine T-Lymphocyte Immune Globulin

Intervention Type: BIOLOGICAL

Given IV

Melphalan

Intervention Type: DRUG

Given IV

Mycophenolate Mofetil

Intervention Type: DRUG

Given PO or IV

Tacrolimus

Intervention Type: DRUG

Given IV

Thiotepa

Intervention Type: DRUG

Given IV

Interventions

Etoposide

Given IV

Intervention Type: DRUG

Fludarabine Phosphate

Given IV

Intervention Type: DRUG

Hematopoietic Cell Transplantation

Undergo HCT

Intervention Type: PROCEDURE

Lapine T-Lymphocyte Immune Globulin

Given IV

Intervention Type: BIOLOGICAL

Melphalan

Given IV

Intervention Type: DRUG

Mycophenolate Mofetil

Given PO or IV

Intervention Type: DRUG

Tacrolimus

Given IV

Intervention Type: DRUG

Thiotepa

Given IV

Intervention Type: DRUG

Other Intervention Names

Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; 2-F-ara-AMP; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; Beneflur; Fludara; SH T 586; HCT; Hematopoietic Stem Cell Transplantation; HSCT; Stem Cell Transplant; stem cell transplantation; Anti-Thymocyte Globulin Rabbit; Grafalon; Rabbit Anti-Human Thymocyte Globulin (RATG); Rabbit Anti-Thymocyte Globulin; Rabbit Antithymocyte Globulin; Rabbit ATG; rATG; Thymoglobulin; 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; CellCept; MMF; FK 506; Fujimycin; Hecoria; Prograf; Protopic; 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

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

• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kris M Mahadeo, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Provided Documents

Document Type: Informed Consent Form

View Document

Related Links

http://www.mdanderson.org

MD Anderson Cancer Center

Other Identifiers

NCI-2020-05878

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-0495

Identifier Type: OTHER

Identifier Source: secondary_id

2020-0495

Identifier Type: -

Identifier Source: org_study_id