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

NCT03635632 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: H-42207 GAIL-N
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 2

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.

Conditions

Relapsed Neuroblastoma; Refractory Neuroblastoma; Relapsed Osteosarcoma; Relapsed Ewing Sarcoma; Relapsed Rhabdomyosarcoma; Uveal Melanoma; Phyllodes Breast Tumor

Keywords

Gene Therapy; CAR T-cells; Neuroblastoma; chimeric antigen receptor; Immunotherapy; Sarcoma; Uveal Melanoma; Breast cancer; GD2 positive cancer

Outcome Measures

Primary Outcomes (1)

• Determine maximum tolerated dose (MTD) of C7R-GD2.CART Cells

  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.

  4 weeks post T cell infusion

Secondary Outcomes (1)

• Determine Anti-tumor Responses

  6 to 8 weeks post T cell infusion

Study Arms (2)

Arm A: High-risk group of patients with lung metastases

EXPERIMENTAL

Patients will be treated at 2 dose levels without lymphodepletion chemotherapy. Three patients will be evaluated and if safety is confirmed patients will be treated at the next dose level with C7R.GD2.CART cell infusion without lymphodepletion chemotherapy. The protocol is divided into two arms, a high-risk group of patients with lung metastases (Arm B) and a standard risk group of all other patients (Arm A). The standard risk Arm A includes osteosarcoma patients without pulmonary disease. Each arm will undergo separate dose escalation.

Genetic: C7R-GD2.CART cells

Arm B: Standard risk group of all other patients

EXPERIMENTAL

Patients will be treated at 2 dose levels without lymphodepletion chemotherapy. Three patients will be evaluated and if safety is confirmed patients will be treated at the next dose level with C7R.GD2.CART cell infusion without lymphodepletion chemotherapy. The protocol is divided into two arms, a high-risk group of patients with lung metastases (Arm B) and a standard risk group of all other patients (Arm A). The standard risk Arm A includes osteosarcoma patients without pulmonary disease. Each arm will undergo separate dose escalation.

Genetic: C7R-GD2.CART cells

Interventions

C7R-GD2.CART cells GENETIC

Active dose levels: C7R-GD2.CART cell without lymphodepletion (Arm A or Arm B) Dose Level 2b = 3 x 10\^7 on day 0 and day 7 Dose Level 3b = 1 x 10\^8 on day 0 and day 7. Day 7 dose (+- 2 days) will be omitted if patients have persistent CRS (Grade 2 or higher) experienced a DLT or for other clinical concerns at the discretion of the PI.

Arm A: High-risk group of patients with lung metastases; Arm B: Standard risk group of all other patients

Eligibility Criteria

• Age: 1 Year - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Evaluable neuroblastoma with persistent or relapsed disease
• Recurrent disease following completion of aggressive multi-drug frontline therapy.
• Progressive disease during aggressive multi-drug frontline therapy.
• 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.
• Life expectancy of at least 12 weeks
• Karnofsky/Lansky score of 50% or greater
• Absence of human anti-mouse antibodies (HAMA) prior to enrollment (only in patients that have been previously treated with murine antibodies or testing pending)
• Informed consent and assent (as applicable) obtained from parent/guardian and child
• Greater than 1 and less than 75 years of age
• Neuroblastoma with persistent or relapsed disease
• Recurrent disease following completion of aggressive multi-drug frontline therapy.

You may not qualify if:

• History of hypersensitivity to murine protein containing products (patients who have undergone desensitization and successful re-challenge without hypersensitivity reaction are eligible)
• Active autoimmune disease (requiring immunosuppressive treatment in the past 6 months)
• Primary brain tumor or known brain metastases (on evaluation by MIBG and/or PET if applicable, CT/MRI/LP not required)
• Currently receiving other investigational drugs.
• Received any investigational immunotherapies or checkpoint inhibitors within 6 weeks. Immunotherapies include adoptive cell therapies, gene therapies, and tumor vaccines.
• History of hypersensitivity to murine protein containing products (patients who have undergone desensitization and successful re-challenge without hypersensitivity reaction are eligible).
• 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). Baseline pulmonary function testing is required in patients with bilateral pulmonary infiltrates (except young children unable to undergo testing). Patients with poor lung function based on PFT testing (Patients with FEV 1, FVC and DLCO/diffusion capacity \< 50%) will not be eligible for treatment on protocol. Patients with intermediate function (FEV 1, FVC and DLCO/diffusion capacity ≥ 50% and \< 70% predicted) will require assessment by a pulmonologist prior to treatment.
• Evidence of tumor potentially causing airway obstruction
• Patients must not be pregnant, lactating, or unwilling to use birth control
• Patients must not be currently receiving immunosuppressive drugs such as corticosteroids (prednisone dose of \> 0.25 mg/kg/day or equivalent), tacrolimus or cyclosporine
• Active autoimmune disease (requiring immunosuppressive treatment in the past 6 months)
• Primary brain tumor or known brain metastases (on evaluation by MIBG and/or PET if applicable, CT/MRI/LP not required)

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator
• Cancer Prevention Research Institute of Texas: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neuroblastoma; Osteosarcoma; Sarcoma, Ewing; Rhabdomyosarcoma; Uveal Melanoma; Phyllodes Tumor; Sarcoma; Breast Neoplasms

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Melanoma; Neuroendocrine Tumors; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Bilal Omer, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: August 17, 2018
• Study Start: April 23, 2019
• Primary Completion: May 16, 2023
• Study Completion (Estimated): May 16, 2038
• Last Updated: July 25, 2025

Record last verified: 2025-07

Locations

US (2)