SJiMB21: Risk-Based Medulloblastoma Treatment for Infants and Young Children

Brief Summary

SJiMB21 is a phase 2 trial that explores the use of molecular and clinical risk-based therapy in the treatment of infants and young children with newly diagnosed medulloblastoma.

Innovations to the contemporary medulloblastoma treatment approach include the use of methylation profiling-based classification to identify clinical risk and reduce treatment intensity for low-risk molecular groups and disease subgroups. Methylation profiling will classify the tumors into molecular groups of SHH and G3/G4 . The SHH tumors will be further subclassified into molecular subgroups SHH-1 and SHH-2.

Participants will be assigned to treatment strata based first on tumor molecular group and subgroup assignment and then by clinical risk.

Patients with SHH-1 who are less than 3 years old will be treated on Stratum S-1. Patients with SHH-2 will be treated on Stratum S-2, and patients in G3/G4 will treated on Stratum N. All patients will receive systemic chemotherapy after surgical resection of the tumor. For stratum S-1 and stratum S-2, the chemotherapy is intended to be curative. These infants will not receive any radiation therapy as part of the protocol. However, Stratum S-1 chemotherapy is more intensified in comparison to stratum S-2. For stratum N, chemotherapy is a radiation-delaying strategy to bridge the patient until they are older than 3 years of age.

This treatment approach attempts to mitigate long-term, therapy-related toxicities in lower-risk patients while preserving positive clinical outcomes (Stratum S-1 and S-2). The trial reserves more toxic therapeutic approaches for those who need them most (Stratum N).

Primary Objectives

• To estimate the progression-free survival of patients after the use of molecular and clinical risk-directed therapy in the treatment of infants and young children with newly diagnosed medulloblastoma.
• To compare cognitive outcomes among infants and young children treated with systemic chemotherapy only with patients treated with systemic chemotherapy and intra-ventricular chemotherapy or delayed risk-adapted radiation therapy.

Learn more about details of this clinical trial

Eligibility Overview

Inclusion criteria for screening include:

• Birth to 5 years old
• Presumed or suspected newly diagnosed medulloblastoma
• Has disease staged by MRI of the brain and spine
• Adequate tumor tissue from primary tumor for central review of pathology

Exclusion criteria for screening include:

• Actively receiving any other investigational agents directed to the tumor/cancer
• Other clinically significant medical disorders, such as serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction that could compromise a patient’s ability to tolerate protocol therapy or would interfere with the study procedures or results

Inclusion criteria for enrollment:

• Confirmed newly diagnosed medulloblastoma (including molecular group of medulloblastoma) by central review done at St. Jude Children’s Research Hospital

Study Sites

St. Jude Children’s Research Hospital
Memphis, Tennessee

About this study

Medulloblastoma in children is a fast-growing tumor. It can be cured in many patients with intense treatment that includes surgery, radiation, and chemotherapy. Very young children with medulloblastoma are divided into 2 molecular groups: SHH and G3/G4. SHH-medulloblastomas are further divided into subgroups SHH-1 and SHH-2. Prior research done at St. Jude and other major institutions has shown that each molecular group and subgroup requires different intensities and types of therapy. St. Jude takes a risk-based treatment approach based on molecular classification and clinical risk.

Cancer therapy often has many long-term side effects. Especially, radiation therapy to the developing brain and spine of infants and young children may cause permanent problems with thinking, learning, and growing. So, it is important to adjust therapy intensity and molecular classification. We strive to give the best chance of cure while reducing the risk of long-term effects and reserve the most intense therapy (such as radiation) for the patients with highest-risk disease.

• Molecular classification defines which molecular group and subgroup the medulloblastoma belongs to.
• Clinical risk is determined by the spread of cancer to other parts of the brain or spine and age of the patient.

For patients who may have low-risk tumors, this approach offers less-intense treatment. Higher-risk patients get more intense treatment.

St. Jude researchers will also study the mental and thinking skills of those treated with chemotherapy only and those treated with chemotherapy and radiation. This can help us identify patients who may have problems in school. We can then educate and guide parents and help patients get extra support when needed.

Purpose of this clinical trial

This study uses a risk-directed approach to find out which types of treatment will work best and have the fewest side effects for infants and children with medulloblastoma.

Eligibility overview

• Birth to 5 years old
• Newly diagnosed medulloblastoma
• Has not had previous radiotherapy, chemotherapy, or other treatment for the brain tumor other than corticosteroid therapy and surgery