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C7R-GD2.CART Cells for Patients With Relapsed or Refractory Neuroblastoma and Other GD2 Positive Cancers (GAIL-N)

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: NCT03635632
Recruitment Status : Recruiting
First Posted : August 17, 2018
Last Update Posted : January 14, 2020
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
Cancer Prevention Research Institute of Texas
Information provided by (Responsible Party):
Bilal Omer, Baylor College of Medicine

Brief Summary:

This study is for patients with neuroblastoma, sarcoma, uveal melanoma, breast cancer, or another cancer that expresses a substance on the cancer cells called GD2. The cancer has either come back after treatment or did not respond to treatment. 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 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 gene into T cells that will make them recognize cancer cells and kill them. In our last clinical trial we made a gene called a chimeric antigen receptor (CAR) from an antibody that recognizes GD2, a substance found on almost all neuroblastoma cells (GD2-CAR). 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 GD2 positive tumor cells.

Therefore, in this study we will add a new gene to the GD2 T cells that can cause the cells to live longer. T cells need substances called cytokines to survive and the cells may not get enough cytokines after infusion. 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 studies using T cells, 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 cancer.


Condition or disease Intervention/treatment Phase
Relapsed Neuroblastoma Refractory Neuroblastoma Relapsed Osteosarcoma Relapsed Ewing Sarcoma Relapsed Rhabdomyosarcoma Uveal Melanoma Phyllodes Breast Tumor Genetic: C7R-GD2.CART cells Drug: Cyclophosphamide Drug: Fludarabine Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 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 Relapsed or Refractory Neuroblastoma and Other GD2 Positive Solid Cancers(GAIL-N)
Actual Study Start Date : April 23, 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : December 2037


Arm Intervention/treatment
Experimental: C7R-GD2.CART cells
This is a single arm study. Patients will be treated at 4 dose levels. At the dose level 0, patients will only receive C7R-GD2.CART cells without lymphodepletion chemotherapy. 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
  • Dose Level 0: 1 x 10^7 C7R-GD2.CART cells without Lymphodepletion
  • Dose Level 1: 1 x 10^7 C7R-GD2.CART cells with Lymphodepletion
  • Dose Level 2: 3 x 10^7 C7R-GD2.CART cells with Lymphodepletion
  • Dose Level 3: 1 x 10^8 C7R-GD2.CART cells with Lymphodepletion

Drug: Cyclophosphamide
If patients receive lymphodepletion, 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
If patients receive lymphodepletion, 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. Determine maximum tolerated dose (MTD) of C7R-GD2.CART Cells [ Time Frame: 6 weeks post T cell infusion ]
    Toxicity will be evaluated as per the NCI CTCAE version 5.0 with the exception of CRS and neurological toxicities that are related to T-cell infusions.


Secondary Outcome Measures :
  1. Determine Anti-tumor Responses [ Time Frame: 6 to 8 weeks post T cell infusion ]
    Number of patients with evaluable/measurable disease who have a partial or complete response according to standard disease evaluation criteria



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:   1 Year to 74 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Procurement Inclusion Criteria:

  1. Evaluable neuroblastoma with persistent or relapsed disease

    1. Recurrent disease following completion of aggressive multi-drug frontline therapy.
    2. Progressive disease during aggressive multi-drug frontline therapy.
    3. Primary resistant/refractory disease (less than partial response by INRC) detected at the conclusion of at least 4 cycles of aggressive multi-drug induction chemotherapy on or according to a standard high-risk treatment protocol

    OR Relapsed or refractory osteosarcoma not responsive to standard treatment

    OR Patients diagnosed with GD2 positive metastatic uveal melanoma and progressed after at least one prior systemic treatment

    OR GD2 positive breast cancer with metastatic or locally recurrent unresectable breast cancer currently progressive after at least two prior lines of therapy in the advanced setting. Patients with HER2+ disease must have failed two or more different anti-HER2 agents.

    OR Patients with other relapsed or refractory solid tumors not responsive to standard treatment with confirmed expression of GD2 by immunohistochemistry testing.

  2. Life expectancy of at least 12 weeks
  3. Karnofsky/Lansky score of 50% or greater
  4. Absence of human anti-mouse antibodies (HAMA) prior to enrollment (only in patients that have been previously treated with murine antibodies)
  5. Informed consent and assent (as applicable) obtained from parent/guardian and child
  6. Greater than 1 and less than 75 years of age

Treatment Inclusion Criteria:

  1. Neuroblastoma with persistent or relapsed disease

    1. Recurrent disease following completion of aggressive multi-drug frontline therapy.
    2. Progressive disease during aggressive multi-drug frontline therapy.
    3. Primary resistant/refractory disease (less than partial response by INRC) detected at the conclusion of at least 4 cycles of aggressive multi-drug induction chemotherapy on or according to a standard high-risk treatment protocol.

    OR Relapsed or refractory osteosarcoma not responsive to standard treatment

    OR Patients diagnosed with GD2 positive metastatic uveal melanoma and progressed after at least one prior systemic treatment

    OR GD2 positive breast cancer with metastatic or locally recurrent unresectable breast cancer currently progressive after at least two prior lines of therapy in the advanced setting. Patients with HER2+ disease must have failed two or more different anti-HER2 agents.

    OR Patients with other relapsed or refractory solid tumors not responsive to standard treatment with confirmed expression of GD2 by immunohistochemistry testing.

  2. Life expectancy of at least 12 weeks
  3. Karnofsky/Lansky score of 50% or greater
  4. Patients must have an ANC ≥ 500, platelet count ≥ 20,000
  5. Pulse Ox ≥ 90% on room air
  6. AST and ALT less than 5 times the upper limit of normal (less than 10 times upper normal if uveal melanoma with metastatic liver disease)
  7. Total bilirubin less than 3 times the upper limit of normal
  8. Serum creatinine less than 3 times upper limit of normal. Creatinine clearance is needed for patients with creatinine greater than 1.5 times upper limit of normal.
  9. At least 4 weeks from completion and recovered from acute effects of all prior chemotherapy. If some effects of therapy have become chronic (i.e., treatment associated thrombocytopenia), the patient must be clinically stable and meet all other eligibility criteria.
  10. Absence of human anti-mouse antibodies (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies
  11. Patients must have autologous activated T-cells with ≥ 20% expressing GD2.CAR
  12. Informed consent and assent (as applicable) obtained from parent/guardian and child
  13. Greater than 1 and less than 75 years of age

Procurement Exclusion Criteria:

  1. History of hypersensitivity to murine protein containing products
  2. History of autoimmune disease (patients with asthma that has not been active for at least 6 months or patients who only have mild eczema are eligible)
  3. Primary brain tumor or known brain metastases (on evaluation by MIBG and/or PET if applicable, CT/MRI/LP not required)

Treatment Exclusion Criteria

  1. Currently receiving other investigational drugs.
  2. Received any investigational immunotherapies or checkpoint inhibitors within 6 weeks. Immunotherapies include adoptive cell therapies, gene therapies, and tumor vaccines.
  3. History of hypersensitivity to murine protein containing products
  4. History of cardiomegaly or bilateral pulmonary infiltrates on chest radiograph or CT. However, patients with cardiomegaly on imaging may be enrolled if they have an assessment of cardiac function (i.e., ECHO or MUGA) within 3 weeks of starting protocol therapy that is within acceptable limits (LVSF>28% or LVEF>50%). Additionally, patients with bilateral pulmonary infiltrates on imaging may be enrolled if the lesions are not consistent with active neuroblastoma (i.e., negative on functional imaging with PET or MIBG, or by pathologic assessment) or not bulky in other diseases (< 5 cm for each lesion) and patient meet FiO2 criteria (>90% on room air).
  5. Evidence of tumor potentially causing airway obstruction
  6. Patients must not be pregnant, lactating, or unwilling to use birth control
  7. Patients must not be currently receiving immunosuppressive drugs such as corticosteroids (prednisone dose of > 0.25 mg/kg/day or equivalent), tacrolimus or cyclosporine
  8. History of autoimmune disease (patients with asthma that has not been active for at least 6 months or patients who only have mild eczema are eligible)
  9. Primary brain tumor or known brain metastases (on evaluation by MIBG and/or PET if applicable, CT/MRI/LP not required)

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): NCT03635632


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

Locations
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United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Bilal Omer, MD    832-824-6855    bomer@bcm.edu   
Contact: David Allen    832-824-4391    dlallen@texaschildrens.org   
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@texaschildrens.org   
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
Cancer Prevention Research Institute of Texas
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: NCT03635632    
Other Study ID Numbers: H-42207 GAIL-N
First Posted: August 17, 2018    Key Record Dates
Last Update Posted: January 14, 2020
Last Verified: January 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
Neuroblastoma
chimeric antigen receptor
Immunotherapy
Sarcoma
Uveal Melanoma
Breast cancer
GD2 positive cancer
Additional relevant MeSH terms:
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Rhabdomyosarcoma
Melanoma
Sarcoma
Neuroblastoma
Osteosarcoma
Sarcoma, Ewing
Breast Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Connective and Soft Tissue
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms by Site
Breast Diseases
Skin Diseases
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Immunosuppressive Agents