3RD GENERATION GD2 SPECIFIC CHIMERIC ANTIGEN RECEPTOR TRANSDUCED AUTOLOGOUS NATURAL KILLER T-CELLS FOR NEUROBLASTOMA

NCT02439788 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: H-33272, GINAKIT
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is for patients that have a cancer called Neuroblastoma that has either come back after treatment or did not respond to the standard medicines used to treat it. This study combines two different ways of fighting cancer: antibodies and Natural Killer T cells. 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. The investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. In a previous clinical trial, the investigators made a gene called a chimeric antigen receptor (CAR), from an antibody called 14g2a that recognizes GD2, a molecule found on almost all neuroblastoma cells (GD2-CAR). They put this gene into the patients' own T cells and gave them back to patients that had neuroblastoma. Nineteen patients were treated on that study and there were no long term side-effects seen after the GD2 T cell infusion. As the investigators have followed the patients over time, they noticed that for those patients with disease at the time of their infusion, the time to progression (the amount of time it takes before their neuroblastoma got worse) was longer in those whom they could find GD2 T cells in the blood for more than 6 weeks after the last T cell infusion. Because of this, the investigators think that if effector cells are able to last longer, they may have a better chance of killing neuroblastoma tumor cells. Natural Killer T cells are a special subset of innate lymphocytes that can effectively go into tumor tissues of neuroblastoma. Inside the tumor, there are certain white blood cells which help the cancer cells to grow and recover from injury. Natural Killer T-cells can specifically kill these cells. In this study, Natural Killer T cells will be genetically engineered to express GD2-CAR to attack neuroblastoma cells and the white blood cells inside the tumor tissue.

Conditions

Neuroblastoma

Keywords

Neuroblastoma; Natural Killer T Cells; Gene Therapy; Chimeric Antigen Receptor

Outcome Measures

Primary Outcomes (1)

• Number of Patients with dose limiting toxicities

  We will assess the MTD and the toxicity of GINAKIT cells adoptively transferred to patients with relapsed/refractory neuroblastoma

  4 weeks

Secondary Outcomes (2)

• Number of patients with a tumor response

  4 weeks

• Number of patients with an immunologic response

  15 years

Study Arms (1)

GINAKIT Cells plus chemotherapy

EXPERIMENTAL

Patients receive chemotherapy with Fludarabine and Cyclophosphamide and then an infusion of the GINAKIT cells (iC9-GD2.CD28.OX40.zeta Natural Killer T cells)

Drug: cyclophosphamide; Drug: Fludarabine; Genetic: GINAKIT Cells

Interventions

cyclophosphamide DRUG

500 mg/m2/day x 2 days; for patients \<12 kg the dose is 16.7 mg/kg/day x 2 days; Cyclophospamide will be given daily starting Day -4 prior to administration of GINAKIT cells.

Also known as: Cytoxan

GINAKIT Cells plus chemotherapy

Fludarabine DRUG

30 mg/m2/day x 3 days; for patients \<12 kg the dose is 1 mg/kg/day x 3 days; Fludarabine will be given daily starting Day -4 prior to administration of GINAKIT cells

GINAKIT Cells plus chemotherapy

GINAKIT Cells GENETIC

* Dose Level 1 = 3 x 10\^6 * Dose Level 2 = 1 x 10\^7 * Dose Level 3 = 3 x 10\^7 * Dose Level 4 = 1 x 10\^8 After the end of the 4 week evaluation period, if subjects have not had a severe side effects and if disease has not gotten worse, the subjects may be offered additional doses of the same cell dose in the future.

Also known as: iC9-GD2.CD28.OX40.zeta Natural Killer T cells

GINAKIT Cells plus chemotherapy

Eligibility Criteria

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

You may qualify if:

• High risk neuroblastoma or persistent or relapsed disease
• Life expectancy of at least 12 weeks
• Age ≥1 and ≤18 years old
• Karnofsky/Lansky score of 60% or greater
• Absence of HAMA prior to enrollment (only in patients that have been previously treated with murine antibodies)
• Ability to tolerate leukocyte apheresis
• Informed consent for leukocyte apheresis
• Informed consent and assent (as applicable) obtained from parent/guardian and child.

You may not qualify if:

• Rapidly progressive disease
• History of hypersensitivity to murine protein containing products
• High risk neuroblastoma with persistent or relapsed disease
• Life expectancy of at least 12 weeks
• Age ≥1 and ≤18 years old
• Karnofsky/Lansky score of 60% or greater
• Patients must have an ANC ≥ 500 without the use G-CSF or GM-CSF for at least 48hrs, platelet count ≥ 20,000
• Pulse Ox ≥ 90% on room air
• AST less than 5 times the upper limit of normal
• Bilirubin less than 3 times the upper limit of normal
• Serum creatinine less than 3 times upper limit of normal
• Recovered from the acute toxic effects of all prior chemotherapy (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria).
• Absence of human anti-mouse antibodies (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies
• Patients must have autologous transduced NKTs with greater than or equal to 20% expression of GD2-specific CAR.
• Informed consent and assent (as applicable) obtained from parent/guardian and child.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• Alex's Lemonade Stand Foundation: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

Cyclophosphamide; fludarabine

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Andras A Heczey, MD

  Baylor College of Medicine - Texas Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 7, 2015
• First Posted: May 12, 2015
• Study Start: August 1, 2017
• Primary Completion: September 1, 2019
• Study Completion (Estimated): October 1, 2030
• Last Updated: June 14, 2017

Record last verified: 2017-06

Locations

US (1)