NCT04521946

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

A Pilot Study of Allogeneic Hematopoietic Cell Transplantation for Patients With High Grade Central Nervous System Malignancies

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 25 Years
• Healthy volunteers: Accepted

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

Interventions

Type	Name	Description
DRUG	Etoposide	Given IV
DRUG	Fludarabine Phosphate	Given IV
PROCEDURE	Hematopoietic Cell Transplantation	Undergo HCT
BIOLOGICAL	Lapine T-Lymphocyte Immune Globulin	Given IV
DRUG	Melphalan	Given IV
DRUG	Mycophenolate Mofetil	Given PO or IV
DRUG	Tacrolimus	Given IV
DRUG	Thiotepa	Given IV

Timeline

• Start date: 2021-01-14
• Primary completion: 2022-12-20
• Completion: 2022-12-20
• First posted: 2020-08-21
• Last updated: 2024-10-26

Regulatory

• FDA-regulated drug study