Chemotherapy and Donor Stem Transplant for the Treatment of Patients With High Grade Brain Cancer
- Conditions
- Interventions
- Registration Number
- NCT04521946
- Lead Sponsor
- M.D. Anderson Cancer Center
- 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, eit...
- Detailed Description
PRIMARY OBJECTIVE:
...
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (chemotherapy, HCT) Hematopoietic Cell Transplantation 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. Treatment (chemotherapy, HCT) Lapine T-Lymphocyte Immune Globulin 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. Treatment (chemotherapy, HCT) Fludarabine Phosphate 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. Treatment (chemotherapy, HCT) Etoposide 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. Treatment (chemotherapy, HCT) Melphalan 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. Treatment (chemotherapy, HCT) Mycophenolate Mofetil 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. Treatment (chemotherapy, HCT) Tacrolimus 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. Treatment (chemotherapy, HCT) Thiotepa 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.
- Primary Outcome Measures
Name Time Method Transplant-related mortality 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 Within 30 days Assessed per Bearman Regimen-Related Toxicities Scale. Will be reported together with the corresponding 95% Bayesian credible interval.
- Secondary Outcome Measures
Name Time Method Failure of platelet and neutrophil engraftment rates Day 100 Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Overall survival 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 At day 180 Cumulative incidence of relapse 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 At day 100 and 1 year 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 Up to day 100 Will be estimated using the method of Gooley.
Rate of grade II organ toxicity Up to day 100 Will be reported as counts with percentages.
Rate of graft failure (primary and secondary) Up to day 100 Will be reported as counts with percentages.
Rate of infectious complications Up to day 100 Will be reported as counts with percentages.
Incidence of chronic GVHD At day 100 and 1 year Will be estimated using the method of Gooley.