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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04099797
Recruitment Status : Recruiting
First Posted : September 23, 2019
Last Update Posted : February 24, 2020
Sponsor:
Collaborator:
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
Bilal Omer, Baylor College of Medicine

Brief Summary:

This study is for patients with high grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG). Because there is no standard treatment for this cancer at this time, patients are being 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 helps the body fight infection.

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients.

We have found from previous research that we 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. When we and other researchers tested DIPG/HGG cancer cells we found that many of these cancers also have GD2 on their surface.

In a clinical trial for a different cancer in children (neuroblastoma), we made a gene called a chimeric antigen receptor (CAR) from an antibody that recognizes GD2. We put this gene into the patients' own T cells and gave them back to 11 neuroblastoma patients. We saw that the cells did grow for a while, but started to disappear from the blood after 2 weeks. We think that if T cells are able to last longer, they may have a better chance of killing tumor cells.

In this study we will add a new gene to the GD2 T cells that can cause the cells to live longer. We know that T cells need substances called cytokines to survive. We have added the gene C7R that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time.

In other clinical studies using T cells, some investigators 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 we think that it will allow the T cells to expand and stay longer in the body, and potentially kill cancer cells more effectively.

The GD2.C7R T cells are an investigational product not approved by the Food and Drug Administration.

The purpose of this study is to find the largest safe dose of GD2-C7R T cells, and also to evaluate how long they can be detected in the blood and what affect they have on DIPG/HGG.


Condition or disease Intervention/treatment Phase
Diffuse Intrinsic Pontine Glioma High Grade Glioma Genetic: (C7R)-GD2.CART cells Drug: Cyclophosphamide Drug: Fludarabine Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 3, 2020
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : February 2038


Arm Intervention/treatment
Experimental: C7R-GD2.CAR T cells
This is a single arm study. Patients will be treated at 4 dose levels. At dose level 0, patients will only receive GD2.CART cells without C7R and they will receive lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine. Three patients will be evaluated and if safety is confirmed patients will be treated with lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine followed by C7R.GD2.CART cell infusion at 3 dose levels.
Genetic: (C7R)-GD2.CART cells
  1. Dose Level 0: 1 x 10^7 GD2.CART cells single transduced without C7R with lymphodepletion chemotherapy
  2. Dose Level 1: 1 x 10^7 C7R-GD2.CART cells with lymphodepletion chemotherapy
  3. Dose Level 2: 3 x 10^7 C7R-GD2.CART cells with lymphodepletion chemotherapy
  4. Dose Level 3: 1 x 10^8 C7R-GD2.CART cells with lymphodepletion chemotherapy

Drug: Cyclophosphamide
Patients at all dose levels will receive lymphodepletion chemotherapy. They will receive 2 daily doses of cyclophosphamide (500mg/m2/day) finishing at least 24 hours before T-cell infusion. The drug will be given intravenously (through an IV needle).
Other Name: Cytoxan

Drug: Fludarabine
Patients at all dose levels will receive lymphodepletion chemotherapy. They will receive 3 daily doses of fludarabine (30mg/m2/day) finishing at least 24 hours before T-cell infusion. The drug will be given intravenously (through an IV needle).
Other Name: Fludara




Primary Outcome Measures :
  1. Dose limiting toxicity (DLT) rate [ Time Frame: 4 weeks post T cell infusion ]
    DLT rate is defined as the proportion of subjects with DLT evaluated as per the NCI CTCAE v5.0 with the exception of CRS and neurological toxicities that are related to T cell infusions.


Secondary Outcome Measures :
  1. Response rate according to standard criteria [ Time Frame: 6 and 12 weeks post T cell infusion ]
    Anti-tumor response to (C7R)-GD2.CART cell therapy will be evaluated by Magnetic Resonance Imaging (MRI)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Procurement Inclusion Criteria:

  1. Patients with histologically confirmed, GD2-expressing newly diagnosed DIPG or HGG or confirmation of positive H3K27M mutation status if sufficient tissue for GD2 staining by IHC is not available.
  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 time of diagnosis
  3. Measurable disease on at least 2 dimensions on MRI
  4. Age 12 months to 18 years
  5. Functional score (Karnofsky/Lansky) ≥ 50 expected at infusion
  6. 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

Procurement Exclusion Criteria:

  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.

Treatment Inclusion Criteria

  1. Patients with histologically confirmed, GD2-expressing newly diagnosed DIPG or HGG or confirmation of positive H3K27M mutation status if sufficient tissue for GD2 staining by IHC is not available.
  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 time of diagnosis
  3. Measurable disease on at least 2 dimensions on MRI
  4. Central line (PICC or other) in place or planned to be placed
  5. Age 12 months to 18 years
  6. Functional score (Karnofsky/Lansky) ≥ 50
  7. Patients must have completed radiation therapy. Radiation therapy 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

Treatment Exclusion Criteria

  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
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04099797


Contacts
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Contact: Bilal Omer, MD 832-824-6855 bomer@bcm.edu
Contact: David Allen 832-824-4391 dlallen@bcm.edu

Locations
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United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Bilal Omer, MD    832-824-6855    bomer@bcm.edu   
Contact: David Allen    832-824-4391    dlallen@bcm.edu   
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
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Principal Investigator: Bilal Omer, MD Baylor College of Medicine

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Responsible Party: Bilal Omer, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT04099797    
Other Study ID Numbers: H-45668 GAIL-B
First Posted: September 23, 2019    Key Record Dates
Last Update Posted: February 24, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bilal Omer, Baylor College of Medicine:
Gene Therapy
CAR T-cells
chimeric antigen receptor
Brain Cancer
Immunotherapy
Glioma
Brain tumor
Additional relevant MeSH terms:
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Brain Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Central Nervous System Diseases
Glioma
Brain Diseases
Nervous System Diseases
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites