Clinical trial · Interventional

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

NCT04521946CI-TRIAL-00081978withdrawnPhase 1ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Why stopped (as posted): No participants enrolled.

Summary

Brief summary (as posted)

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.

Conditions

Conditions (15)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Anaplastic Ependymoma	Anaplastic Ependymoma	ONTOLOGY_EXACT	0.90
Atypical Teratoid/Rhabdoid Tumor	Atypical Teratoid/Rhabdoid Tumor	ONTOLOGY_EXACT	0.90
Central Nervous System Germ Cell Tumor	Central Nervous System Germ Cell Tumor	ONTOLOGY_EXACT	0.90
Choroid Plexus Carcinoma	Choroid Plexus Carcinoma	ONTOLOGY_EXACT	0.98
Intracranial Myeloid Sarcoma	Intracranial Myeloid Sarcoma	ONTOLOGY_EXACT	0.98
Malignant Brain Neoplasm	Malignant Brain Neoplasm	ONTOLOGY_EXACT	0.90
Malignant Glioma	Malignant Glioma	ONTOLOGY_EXACT

Interventions

Interventions (8)

Intervention	Type	Mapped drug	Match
Etoposide	Drug	Etoposide	ALIAS
Fludarabine Phosphate	Drug	Fludarabine	ALIAS
Hematopoietic Cell Transplantation	Procedure	—	UNRESOLVED
Lapine T-Lymphocyte Immune Globulin	Biological	—	UNRESOLVED
Melphalan	Drug	Melphalan	ALIAS
Mycophenolate Mofetil	Drug	—	UNRESOLVED
Tacrolimus	Drug	—	UNRESOLVED
Thiotepa	Drug	Thiotepa	ALIAS

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
Treatment (chemotherapy, HCT)
description
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.
interventionNames
1. Drug: Etoposide
2. Drug: Fludarabine Phosphate
3. Procedure: Hematopoietic Cell Transplantation
4. Biological: Lapine T-Lymphocyte Immune Globulin
5. Drug: Melphalan
6. Drug: Mycophenolate Mofetil
7. Drug: Tacrolimus
8. Drug: Thiotepa

Primary outcomes (2)

measure
Transplant-related mortality
timeFrame
At day 30
description

Eligibility

Eligibility (as posted)

Sex: All
Maximum age: 25 Years

Show eligibility criteria text

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

References

Publications (0)

Data not yet available

No reference posted for this study.