Anaplastic EpendymomaPhase 1NCT04521946
Chemotherapy and Donor Stem Transplant for the Treatment of Patients With High Grade Brain Cancer
A Phase 1 study testing Etoposide, Fludarabine Phosphate and Hematopoietic Cell Transplantation in people with Anaplastic Ependymoma and Atypical Teratoid/Rhabdoid Tumor, run by M.D. Anderson Cancer Center.
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. Read more about this study
- Who is it for?
- Ages Up to 25 yearsHealthy volunteers can take part
- Conditions the study is for
- Anaplastic Ependymoma, Atypical Teratoid/Rhabdoid Tumor, Central Nervous System Germ Cell Tumor
- What is being tested?
- Etoposide, Fludarabine Phosphate and Hematopoietic Cell Transplantation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 14 Jan 2021to 20 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 25 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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)
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- 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)
Who cannot join
- 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
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- 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
About this study
Official title: A Pilot Study of Allogeneic Hematopoietic Cell Transplantation for Patients With High Grade Central Nervous System Malignancies
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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
- Being tested
- Etoposide, Fludarabine Phosphate, Hematopoietic Cell Transplantation, Lapine T-Lymphocyte Immune Globulin, Melphalan
- Medical subject headings
- Ependymoma, Rhabdoid Tumor, Choroid Plexus Carcinoma, Brain Neoplasms, Glioma, Medulloblastoma, Neuroectodermal Tumors, Primitive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtoposideDrug
Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar
Given IV
Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara
Given IV
Hematopoietic Cell TransplantationProcedure or surgery
Also called HCT, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant
Undergo HCT
Lapine T-Lymphocyte Immune GlobulinBiological
Also called Anti-Thymocyte Globulin Rabbit, Grafalon, Rabbit Anti-Human Thymocyte Globulin (RATG), Rabbit Anti-Thymocyte Globulin
Given IV
MelphalanDrug
Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard
Given IV
Also called CellCept, MMF
Given PO or IV
TacrolimusDrug
Also called FK 506, Fujimycin, Hecoria, Prograf
Given IV
ThiotepaDrug
Also called 1,1'',1''''-Phosphinothioylidynetrisaziridine, Girostan, N,N'', N''''-Triethylenethiophosphoramide, Oncotiotepa
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (chemotherapy, HCT) | Experimental | 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. Receives: Drug: Etoposide; Drug: Fludarabine Phosphate; Procedure: Hematopoietic Cell Transplantation; Biological: Lapine T-Lymphocyte Immune Globulin; Drug: Melphalan; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Drug: Thiotepa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transplant-related mortality
Will be reported together with the corresponding 95% Bayesian credible interval. Will be estimated using the method of Gooley.
Measured: At day 30
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.
Measured: Within 30 days
Secondary outcomes (10)
Failure of platelet and neutrophil engraftment rates
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Measured: Day 100
Incidence of acute graft-versus-host (GVHD) disease
Will be estimated using the method of Gooley.
Measured: Up to day 100
Incidence of chronic GVHD
Will be estimated using the method of Gooley.
Measured: At day 100 and 1 year
Rate of grade II organ toxicity
Will be reported as counts with percentages.
Measured: Up to day 100
Rate of graft failure (primary and secondary)
Will be reported as counts with percentages.
Measured: Up to day 100
Rate of infectious complications
Will be reported as counts with percentages.
Measured: Up to day 100
Progression free survival
Measured: At day 180
Cumulative incidence of relapse
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Measured: At day 100 and 1 year
Overall survival
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Measured: At day 100 and 1 year
Progression-free survival
Will be calculated and illustrated from the time of transplant by the method of Kaplan and Meier.
Measured: At day 100 and 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2020
- Study start14 Jan 2021
- Primary completion20 Dec 2022
- Study completion20 Dec 2022
Why it stopped: No participants enrolled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anaplastic EpendymomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kris M Mahadeo, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04521946
- Sponsor's protocol ID
- 2020-0495
- Other IDs
- NCI-2020-05878, 2020-0495
- Status last verified
- Oct 2023
- First submitted
- 18 Aug 2020
- Last updated
- 26 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Allogeneic Hematopoietic Cell Transplantation for Patients With High Grade Central Nervous System Malignancies
- ClinicalTrials.gov ID
- NCT04521946
- Acronym / sponsor ID
- 2020-0495
- Conditions
- Anaplastic Ependymoma, Atypical Teratoid/Rhabdoid Tumor, Central Nervous System Germ Cell Tumor, Choroid Plexus Carcinoma, Intracranial Myeloid Sarcoma, Malignant Brain Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No participants enrolled.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 14 Jan 2021 (actual)
- Primary completion
- 20 Dec 2022 (actual)
- Study completion
- 20 Dec 2022 (actual)
- First posted
- 21 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (chemotherapy, HCT) | Experimental | Drug: Etoposide, Drug: Fludarabine Phosphate, Procedure: Hematopoietic Cell Transplantation, Biological: Lapine T-Lymphocyte Immune Globulin, Drug: Melphalan, Drug: Mycophenolate Mofetil, Drug: Tacrolimus, Drug: ThiotepaPatients 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. |
Who may qualify
- Ages
- Up to 25 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EtoposideAlso: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, ToposarGiven IV | Drug | Treatment (chemotherapy, HCT) |
| Fludarabine PhosphateAlso: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, FludaraGiven IV | Drug | Treatment (chemotherapy, HCT) |
| Hematopoietic Cell TransplantationAlso: HCT, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell TransplantUndergo HCT | Procedure or surgery | Treatment (chemotherapy, HCT) |
| Lapine T-Lymphocyte Immune GlobulinAlso: Anti-Thymocyte Globulin Rabbit, Grafalon, Rabbit Anti-Human Thymocyte Globulin (RATG), Rabbit Anti-Thymocyte GlobulinGiven IV | Biological | Treatment (chemotherapy, HCT) |
| MelphalanAlso: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine MustardGiven IV | Drug | Treatment (chemotherapy, HCT) |
| Mycophenolate MofetilAlso: CellCept, MMFGiven PO or IV | Drug | Treatment (chemotherapy, HCT) |
| TacrolimusAlso: FK 506, Fujimycin, Hecoria, PrografGiven IV | Drug | Treatment (chemotherapy, HCT) |
| ThiotepaAlso: 1,1'',1''''-Phosphinothioylidynetrisaziridine, Girostan, N,N'', N''''-Triethylenethiophosphoramide, OncotiotepaGiven IV | Drug | Treatment (chemotherapy, HCT) |
Primary outcome
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.
10 secondary outcomes
Failure of platelet and neutrophil engraftment rates
Time frame: Day 100
Incidence of acute graft-versus-host (GVHD) disease
Time frame: Up to day 100
Incidence of chronic GVHD
Time frame: At day 100 and 1 year
Rate of grade II organ toxicity
Time frame: Up to day 100
Rate of graft failure (primary and secondary)
Time frame: Up to day 100
Rate of infectious complications
Time frame: Up to day 100
Progression free survival
Time frame: At day 180
Cumulative incidence of relapse
Time frame: At day 100 and 1 year
Overall survival
Time frame: At day 100 and 1 year
Progression-free survival
Time frame: At day 100 and 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2024.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kris M Mahadeo, MD principal investigator
M.D. Anderson Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Etoposide, Fludarabine Phosphate and Hematopoietic Cell Transplantation in people with Anaplastic Ependymoma and Atypical Teratoid/Rhabdoid Tumor, run by M.D. Anderson Cancer Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 26 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Transplant-related mortality (time frame: At day 30). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2024.