What is the mechanism of action of this treatment?

The most common treatments for Atypical Teratoid/Rhabdoid Tumor (ATRT) include high-dose chemotherapy, radiation therapy, and autologous peripheral blood stem cell transplant (APBSCT). High-dose chemotherapy and radiation therapy aim to destroy cancer cells by either killing them or preventing their division. APBSCT is used to replace the blood-forming cells that are destroyed during these aggressive treatments. This combination is particularly important for ATRT patients as it allows for intensive treatment of the tumor while enabling recovery of the bone marrow and immune system, which are critical for the patient's overall recovery and long-term health.

What side effects are associated with this type of intervention?

The most common treatments for Atypical Teratoid/Rhabdoid Tumor (ATRT) involving autologous peripheral blood stem cell transplant (APBSCT) include high-dose chemotherapy and radiation therapy. These treatments can cause side effects such as nausea, vomiting, hair loss, fatigue, and increased risk of infections due to bone marrow suppression. Radiation therapy may lead to skin irritation, fatigue, and potential damage to surrounding tissues and organs. The APBSCT procedure itself can result in complications like infections and organ damage. Long-term effects may include endocrine disorders, growth disturbances, and secondary cancers.

What prior FDA approvals exist?

There is limited specific information on FDA approvals for the treatment of Atypical Teratoid/Rhabdoid Tumor (AT/RT) using autologous peripheral blood stem cell transplant (APBSCT). However, high-dose chemotherapy regimens followed by APBSCT are commonly used in treating various aggressive pediatric tumors, including AT/RT. These regimens often include drugs like cyclophosphamide, melphalan, and thiotepa, which are used to eradicate cancer cells before stem cell transplantation. The combination of these chemotherapeutic agents with APBSCT aims to improve survival rates by allowing higher doses of chemotherapy to be administered.

What other types of research exist?

Promising novel alternatives to Autologous Peripheral Blood Stem Cell Transplant for ATRT patients include Chimeric Antigen Receptor (CAR) T-cell therapy, which has shown high rates of durable complete remission in other refractory B-cell lymphomas, and targeted therapies such as CD19 CAR-T cell immunotherapy. These therapies leverage the patient's immune system to target and destroy cancer cells, offering a potentially effective treatment with a different mechanism of action compared to traditional stem cell transplants.

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Combination Therapy for Rhabdoid Tumor

Phase 3

Waitlist Available

Led By Alyssa T Reddy

Research Sponsored by Children's Oncology Group

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Diagnosis of CNS atypical teratoid/rhabdoid tumor (AT/RT) or tumors that have a mutation of the INI1 gene (even if the tumor does not have the usual histologic characteristics of AT/RT)

No evidence of dyspnea at rest

Must not have

No prior radiotherapy or chemotherapy except for the following:

Patients with extra neural metastasis (M4) or renal rhabdoid tumors are not eligible

Timeline

Screening 3 weeks

Treatment Varies

Follow Up during and after completion of study treatment up to 1 year after enrollment.

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial uses a combination of strong drugs, targeted radiation, and a special stem cell procedure to treat young patients with a rare and aggressive brain tumor. The treatment aims to stop cancer growth, destroy cancer cells, and help the body recover by using the patient's own stem cells.

Who is the study for?

This trial is for young patients with a rare brain tumor called atypical teratoid/rhabdoid tumor, or those with INI1 gene mutation. They should have no extra neural metastasis, a life expectancy over 8 weeks, normal organ function tests, and not be pregnant. Patients must use contraception and have had surgery within the past month.

What is being tested?

The study tests high-dose chemotherapy combined with radiation therapy followed by an autologous stem cell transplant to treat the cancer. It aims to see how well these treatments work together in stopping cancer growth by destroying or preventing division of cancer cells.

What are the potential side effects?

Possible side effects include damage to bone marrow (leading to low blood counts), increased risk of infections due to weakened immune system, potential harm to organs from high-dose chemotherapy, fatigue from treatment regimen, and complications related to stem cell transplantation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My tumor is diagnosed as AT/RT or has an INI1 gene mutation.

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I do not have trouble breathing when I am resting.

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My liver enzymes are within normal limits for my age.

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My bilirubin levels are within normal range for my age.

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I had or will have a brain MRI before and after using a contrast agent, close to my surgery date.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't had radiotherapy or chemotherapy before.

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I do not have cancer spread beyond the nervous system or a kidney rhabdoid tumor.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ during protocol therapy up to 1 year after enrollment.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~during protocol therapy up to 1 year after enrollment.

This trial's timeline: 3 weeks for screening, Varies for treatment, and during protocol therapy up to 1 year after enrollment. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Event-free Survival

Overall Survival (OS)

Toxic Death

Secondary study objectives

Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm II (chemotherapy, 3D-CRT, autologous PBSC)Experimental Treatment12 Interventions

Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers. Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (chemotherapy, autologous PBSC, 3D-CRT)Experimental Treatment12 Interventions

Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers. Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Filgrastim

2000

Completed Phase 3

~3690

Cyclophosphamide

2010

Completed Phase 4

~2310

Autologous Hematopoietic Stem Cell Transplantation

2017

Completed Phase 3

~2090

Cisplatin

2013

Completed Phase 3

~3120

Leucovorin Calcium

2011

Completed Phase 3

~12500

Methotrexate

2019

Completed Phase 4

~4400

Vincristine Sulfate

2005

Completed Phase 3

~10270

Carboplatin

2014

Completed Phase 3

~6120

Etoposide

2010

Completed Phase 3

~2960

3-Dimensional Conformal Radiation Therapy

2010

Completed Phase 3

~7490

Thiotepa

2008

Completed Phase 3

~2120

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Atypical Teratoid/Rhabdoid Tumor (ATRT) include high-dose chemotherapy, radiation therapy, and autologous peripheral blood stem cell transplant (APBSCT). High-dose chemotherapy and radiation therapy aim to destroy cancer cells by either killing them or preventing their division. APBSCT is used to replace the blood-forming cells that are destroyed during these aggressive treatments. This combination is particularly important for ATRT patients as it allows for intensive treatment of the tumor while enabling recovery of the bone marrow and immune system, which are critical for the patient's overall recovery and long-term health.

The long-term outcome of patients who relapse after chemotherapy for non-seminomatous germ cell tumours.