RECRUITING

C7R-GD2.CAR T Cells for Patients With GD2-expressing Brain Tumors (GAIL-B)

Conditions

Diffuse Intrinsic Pontine Glioma High Grade Glioma Embryonal Tumor Ependymal Tumor Gene Therapy CAR T-cells chimeric antigen receptor Brain Cancer Immunotherapy Glioma Brain tumor DIPG ETMRs Medulloepithelioma Atypical teratoid/rhabdoid tumors

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

In this study, there are two treatment groups called Cohort 1 and Cohort 2. Cohort 1 is for patients with diffuse midline glioma, high grade glioma, diffuse intrinsic pontine glioma, medulloblastoma, or another rare brain cancer that expresses GD2. Cohort 2 is for patients with a type of cancer called progressive pontine diffuse midline glioma (DMG), high grade glioma or diffuse intrinsic pontine glioma that expresses GD2. Because there is no standard treatment at this time, patients are asked to volunteer in a gene transfer research study using special immune cells called T cells. T cells are a type of white blood cell that help the body fight infection. This research study combines two different ways of fighting cancer: antibodies and T cells. Both antibodies and T cells have been used to treat cancer patients. They have shown promise but have not been strong enough to cure most patients. Researchers have found from previous research that they can put a new antibody gene into T cells that will make them recognize cancer cells and kill them. GD2 is a protein found on several different cancers. Researchers testing brain cancer cells found that many of these cancers also have GD2 on their surface. In a study for neuroblastoma in children, a gene called a chimeric antigen receptor (CAR) was made from an antibody that recognizes GD2. This gene was put into the patients own T cells and given back to 11 patients. The cells did grow for a while but started to disappear from the blood after 2 weeks. The researchers think that if T cells are able to last longer they may have a better chance of killing tumor cells. In this study, a new gene will be added to the GD2 T cells that can cause the cells to live longer. T cells need substances called cytokines to survive. The gene C7R has been added that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time. In other studies using T cells researchers found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body and therefore the effect the T cells can have. This is called lymphodepletion and it will allow the T cells to expand and stay longer in the body and potentially kill cancer cells more effectively. After treating 11 patients, the largest safe dose of GD2-CAR T cells given in the vein (IV) was determined. Going forward, we will combine IV infusions with infusions directly into the brain through the Ommaya reservoir or programmable VP shunt. The goal is to find the largest safe dose of GD2-C7R T cells that can be administered in this way. Patients will now be assigned to Cohort 1 and 2 based on their tumor type with different dose levels for each cohort. The GD2.C7R T cells are an investigational product not approved by the FDA. The purpose of this study is to combine infusions into the vein in the first treatment cycle with infusions directly into the cerebrospinal fluid (CSF) in the brain (intracerebroventricularly) through the ommaya reservoir or programmable VP shunt for the second infusion cycle and possibly additional infusions after that. The goal is to find the largest safe dose of GD2-C7R T cells that can be administered in this way, and additionally to evaluate how long they can be detected in the blood and CSF and what affect they have on brain cancer.

Official Title

Phase I Study of Autologous T Lymphocytes Expressing GD2-specific Chimeric Antigen and Constitutively Active IL-7 Receptors for the Treatment of Patients With GD2-expressing Brain Tumors (GAIL-B)

Quick Facts

Study Start:2020-02-03

Study Completion:2039-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04099797

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Months to 22 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
1. Histologically confirmed, GD2-expressing newly diagnosed DMG/HGG (including pontine) or confirmation of positive H3K27M alteration status if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence. 2. Tumors less than 5 cm in maximum dimension at enrollment 1. Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study 2. Tumors with \>25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤ 25% increased compared with pre-irradiation MRI. 3. Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked 3. Measurable disease on at least 2 dimensions on MRI 4. Age 12 months to 22 years 5. Functional score (Karnofsky/Lansky) ≥ 50 expected at infusion (≥60 for cohort 2)	1. Patients who are pregnant or breast feeding 2. Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator. 1. Histologically confirmed, GD2-expressing newly diagnosed DMG/HGG (including pontine) or confirmation of positive H3K27M alteration status if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence. 2. Tumors less than 5 cm in maximum dimension at enrollment 1. Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study 2. Tumors with \>25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤ 25% increased compared pre-irradiation MRI 3. Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked 3. Measurable disease on at least 2 dimensions on MRI 4. Central line (PICC or other) and Ommaya reservoir or VP shunt in place or planned to be placed 5. Age 12 months to 22 years 6. Functional score (Karnofsky/Lansky) ≥ 50 (≥60 for cohort 2) 7. Patients must have completed radiation therapy at least 4 weeks prior to administration of investigational agent. Radiation therapy and (If applicable) bevacizumab treatment for radiation necrosis must be completed at least 4 weeks prior to administration of investigational agent. 8. Stable neurologic exam for 7 days prior to enrollment 9. Stable or decreasing dose of steroids (max. allowable dose of dexamethasone is 0.1 mg/kg/day over the past 7 days prior to infusion of investigational therapy) 10. Organ function: 1. ANC \> 1000 cells/ul 2. Platelet count \> 100,000 cells/ul 3. Total bilirubin \< 1.5x ULN 4. ALT and AST \< 5x ULN 5. Serum creatinine or kidney within 2x ULN for age 1. Patients who received any other forms of immunotherapy ≤ 42 days before administration of investigational agent 2. Patients who received colony-stimulating factors within 14 days prior to administration of lymphodepletion 3. Patients receiving any concurrent anti-cancer therapy (it is preferable for patients to stop any concurrent anti-cancer therapy at least three half-lives prior to treatment) 4. Patients who are pregnant or breast feeding 5. Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator.

Inclusion Criteria

Exclusion Criteria

1. Histologically confirmed, GD2-expressing newly diagnosed DMG/HGG (including pontine) or confirmation of positive H3K27M alteration status if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence.
2. Tumors less than 5 cm in maximum dimension at enrollment
1. Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study
2. Tumors with \>25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤ 25% increased compared with pre-irradiation MRI.
3. Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked
3. Measurable disease on at least 2 dimensions on MRI
4. Age 12 months to 22 years
5. Functional score (Karnofsky/Lansky) ≥ 50 expected at infusion (≥60 for cohort 2)

1. Patients who are pregnant or breast feeding
2. Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator.
1. Histologically confirmed, GD2-expressing newly diagnosed DMG/HGG (including pontine) or confirmation of positive H3K27M alteration status if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence.
2. Tumors less than 5 cm in maximum dimension at enrollment
1. Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study
2. Tumors with \>25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤ 25% increased compared pre-irradiation MRI
3. Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked
3. Measurable disease on at least 2 dimensions on MRI
4. Central line (PICC or other) and Ommaya reservoir or VP shunt in place or planned to be placed
5. Age 12 months to 22 years
6. Functional score (Karnofsky/Lansky) ≥ 50 (≥60 for cohort 2)
7. Patients must have completed radiation therapy at least 4 weeks prior to administration of investigational agent. Radiation therapy and (If applicable) bevacizumab treatment for radiation necrosis must be completed at least 4 weeks prior to administration of investigational agent.
8. Stable neurologic exam for 7 days prior to enrollment
9. Stable or decreasing dose of steroids (max. allowable dose of dexamethasone is 0.1 mg/kg/day over the past 7 days prior to infusion of investigational therapy)
10. Organ function:
1. ANC \> 1000 cells/ul
2. Platelet count \> 100,000 cells/ul
3. Total bilirubin \< 1.5x ULN
4. ALT and AST \< 5x ULN
5. Serum creatinine or kidney within 2x ULN for age
1. Patients who received any other forms of immunotherapy ≤ 42 days before administration of investigational agent
2. Patients who received colony-stimulating factors within 14 days prior to administration of lymphodepletion
3. Patients receiving any concurrent anti-cancer therapy (it is preferable for patients to stop any concurrent anti-cancer therapy at least three half-lives prior to treatment)
4. Patients who are pregnant or breast feeding
5. Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator.

Contacts and Locations

Study Contact

Bilal Omer, MD

CONTACT

832-824-6855

bomer@bcm.edu

David Allen

CONTACT

832-824-4391

dlallen@bcm.edu

Principal Investigator

Bilal Omer, MD

PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Study Locations (Sites)

Texas Children's Hospital

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Baylor College of Medicine

Bilal Omer, MD, PRINCIPAL_INVESTIGATOR, Baylor College of Medicine

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-02-03

Study Completion Date2039-02

Study Record Updates

Study Start Date2020-02-03

Study Completion Date2039-02

Terms related to this study

Keywords Provided by Researchers

Gene Therapy
CAR T-cells
chimeric antigen receptor
Brain Cancer
Immunotherapy
Glioma
Brain tumor
DIPG
ETMRs
Medulloepithelioma
Atypical teratoid/rhabdoid tumors

Additional Relevant MeSH Terms

Diffuse Intrinsic Pontine Glioma
High Grade Glioma
Embryonal Tumor
Ependymal Tumor