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Modified Immune Cells (C7R-GD2.CART) for the Treatment of GD2 Positive Relapsed or Refractory Solid Cancers

Trial Status: Active

This phase I trial is to find out the best dose, possible benefits and / or side effects of C7R-GD2.CART in treating patients with GD2 positive solid cancer that have come back (relapsed) or do not respond to treatment (refractory). The body has different ways of fighting infection and disease. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. Putting a new gene into T cells may make them recognize cancer cells and kill them. Chimeric antigen receptor (CAR) was made from an antibody that recognizes GD2, a lipid found on almost all neuroblastoma cells (GD2-CAR). T cells need substances called cytokines to survive and the cells may not get enough cytokines after infusion into the body. Adding the gene C7R, gives the cells a constant supply of cytokine and helps them to survive for a longer period of time.

Inclusion Criteria

  • PROCUREMENT: 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 International Neuroblastoma Response Criteria [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
  • PROCUREMENT: Relapsed or refractory osteosarcoma not responsive to standard treatment
  • PROCUREMENT: Patients diagnosed with GD2 positive metastatic uveal melanoma and progressed after at least one prior systemic treatment
  • PROCUREMENT: 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
  • PROCUREMENT: Patients with other relapsed or refractory solid tumors not responsive to standard treatment with confirmed expression of GD2 by immunohistochemistry testing
  • PROCUREMENT: Life expectancy of at least 12 weeks
  • PROCUREMENT: Karnofsky/Lansky score of 50% or greater
  • PROCUREMENT: Absence of human anti-mouse antibodies (HAMA) prior to enrollment (only in patients that have been previously treated with murine antibodies)
  • PROCUREMENT: Informed consent and assent (as applicable) obtained from parent/guardian and child
  • PROCUREMENT: Greater than 1 and less than 75 years of age
  • TREATMENT: 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
  • TREATMENT: Relapsed or refractory osteosarcoma not responsive to standard treatment
  • TREATMENT: Patients diagnosed with GD2 positive metastatic uveal melanoma and progressed after at least one prior systemic treatment
  • TREATMENT: 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
  • TREATMENT: Patients with other relapsed or refractory solid tumors not responsive to standard treatment with confirmed expression of GD2 by immunohistochemistry testing
  • TREATMENT: Life expectancy of at least 12 weeks
  • TREATMENT: Karnofsky/Lansky score of 50% or greater
  • TREATMENT: Absolute neutrophil count (ANC) >= 500 (within 10 days prior to initiation of study related treatment [except for verification of T cells transduction])
  • TREATMENT: Platelet count >= 20,000 (within 10 days prior to initiation of study related treatment [except for verification of T cells transduction])
  • TREATMENT: Pulse oxygen (Ox) >= 90% on room air
  • TREATMENT: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 5 times the upper limit of normal (less than 10 times upper normal if uveal melanoma with metastatic liver disease) (within 10 days prior to initiation of study related treatment [except for verification of T cells transduction])
  • TREATMENT: Total bilirubin less than 3 times the upper limit of normal (within 10 days prior to initiation of study related treatment [except for verification of T cells transduction])
  • TREATMENT: 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 (within 10 days prior to initiation of study related treatment [except for verification of T cells transduction])
  • TREATMENT: 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. Maintenance therapy with non-investigational oral antineoplastic drugs is allowed up to 48 hours prior to infusion
  • TREATMENT: Absence of human anti-mouse antibodies (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies
  • TREATMENT: Patients must have autologous activated T-cells with >= 20% expressing GD2.CAR
  • TREATMENT: Informed consent and assent (as applicable) obtained from parent/guardian and child
  • TREATMENT: Greater than 1 and less than 75 years of age

Exclusion Criteria

  • PROCUREMENT: History of hypersensitivity to murine protein containing products (patients who have undergone desensitization and successful re-challenge without hypersensitivity reaction are eligible)
  • PROCUREMENT: Active autoimmune disease (requiring immunosuppressive treatment in the past 6 months)
  • PROCUREMENT: Primary brain tumor or known brain metastases (on evaluation by iobenguane [MIBG] and/or positron emission tomography [PET] if applicable, computed tomography [CT]/magnetic resonance imaging [MRI]/lumbar puncture [LP] not required)
  • TREATMENT: Currently receiving other investigational drugs
  • TREATMENT: Received any investigational immunotherapies or checkpoint inhibitors within 6 weeks. Immunotherapies include adoptive cell therapies, gene therapies, and tumor vaccines
  • TREATMENT: History of hypersensitivity to murine protein containing products (patients who have undergone desensitization and successful re-challenge without hypersensitivity reaction are eligible)
  • TREATMENT: 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., echocardiography [ECHO] or multigated acquisition [MUGA]) within 3 weeks of starting protocol therapy that is within acceptable limits (left ventricular systolic function (LVSF) > 28% or left ventricular ejection fraction [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 forced expiratory volume [FEV] 1, forced vital capacity [FVC] and diffusion capacity of the lung for carbon monoxide [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
  • TREATMENT: Evidence of tumor potentially causing airway obstruction
  • TREATMENT: Patients must not be pregnant, lactating, or unwilling to use birth control
  • TREATMENT: Patients must not be currently receiving immunosuppressive drugs such as corticosteroids (prednisone dose of > 0.25 mg/kg/day or equivalent), tacrolimus or cyclosporine
  • TREATMENT: Active autoimmune disease (requiring immunosuppressive treatment in the past 6 months)
  • TREATMENT: Primary brain tumor or known brain metastases (on evaluation by MIBG and/or PET if applicable, CT/MRI/LP not required)

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: ACTIVE
Contact: Bilal A. Omer
Phone: 832-824-6855
Center for Cell and Gene Therapy
Status: ACTIVE
Contact: Bilal A. Omer
Phone: 832-824-6855
Texas Children's Hospital
Status: ACTIVE
Contact: Bilal A. Omer
Phone: 832-824-6855

PRIMARY OBJECTIVE:

I. To determine the safety of escalating doses of autologous T cells modified to express a second generation chimeric antigen receptor for GD2 combined with a constitutively active IL7 receptor (autologous active IL-7 receptor co-expressing GD2-specific CAR T-cells [C7R-GD2.CART cells]), administered to patients with relapsed or refractory GD2 expressing cancers.

SECONDARY OBJECTIVE:

I. To estimate the anti-tumor response of autologous C7R-GD2.CART cells in patients with relapsed / refractory GD2 expressing cancers.

EXPLORATORY OBJECTIVE:

I. To evaluate the fate and immunologic effects of C7R-GD2.CART cells administered to patients with relapsed/refractory GD2 expressing cancers.

OUTLINE: This is a dose-escalation study of C7R-GD2.CART.

Patients receive cyclophosphamide intravenously (IV) on days -4 and -3 and fludarabine IV on days -4 to -2. Patients also receive C7R-GD2.CART cells over 1-10 minutes on day 0 in the absence of diseases progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1, 2, 4, 6, and 8 weeks and 3, 6, 9, and 12 months, twice yearly for 4 years, and then annually for 10 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Bilal A. Omer

  • Primary ID GAIL-N
  • Secondary IDs NCI-2021-01065
  • Clinicaltrials.gov ID NCT03635632