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Recruitment Status : Withdrawn (No participants enrolled.)
First Posted : August 21, 2020
Last Update Posted : December 22, 2022
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|Condition or disease||Intervention/treatment||Phase|
|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||Drug: Etoposide Drug: Fludarabine Phosphate Procedure: Hematopoietic Cell Transplantation Biological: Lapine T-Lymphocyte Immune Globulin Drug: Melphalan Drug: Mycophenolate Mofetil Drug: Tacrolimus Drug: Thiotepa||Phase 1|
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.
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.
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Allogeneic Hematopoietic Cell Transplantation for Patients With High Grade Central Nervous System Malignancies|
|Actual Study Start Date :||January 14, 2021|
|Actual Primary Completion Date :||December 20, 2022|
|Actual Study Completion Date :||December 20, 2022|
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.
Drug: Fludarabine Phosphate
Procedure: Hematopoietic Cell Transplantation
Biological: Lapine T-Lymphocyte Immune Globulin
Drug: Mycophenolate Mofetil
Given PO or IV
- 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.
- 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.
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|Ages Eligible for Study:||up to 25 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||Yes|
- 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)
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04521946
|Principal Investigator:||Kris M Mahadeo, MD||M.D. Anderson Cancer Center|
|Responsible Party:||M.D. Anderson Cancer Center|
|Other Study ID Numbers:||
NCI-2020-05878 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2020-0495 ( Other Identifier: M D Anderson Cancer Center )
|First Posted:||August 21, 2020 Key Record Dates|
|Last Update Posted:||December 22, 2022|
|Last Verified:||August 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Neuroectodermal Tumors, Primitive
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Complex and Mixed