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

Malignant Glioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04521946
• Other study ID #: 2020-0495
• Secondary ID: NCI-2020-0587820
• Status: Withdrawn
• Phase: Phase 1
• Start date: January 14, 2021
• Est. completion date: December 20, 2022

Study information

• Verified date: October 2023
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 20, 2022
• Est. primary completion date: December 20, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 25 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Etoposide
Given IV
• Fludarabine Phosphate
Given IV

Procedure:
• Hematopoietic Cell Transplantation
Undergo HCT

Biological:
• Lapine T-Lymphocyte Immune Globulin
Given IV

Drug:
• Melphalan
Given IV
• Mycophenolate Mofetil
Given PO or IV
• Tacrolimus
Given IV
• Thiotepa
Given IV

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center

Outcome

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

External Links

•   MD Anderson Cancer Center