GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma (GINAKIT2)
|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: NCT03294954|
Recruitment Status : Recruiting
First Posted : September 27, 2017
Last Update Posted : January 28, 2020
This research study combines two different ways of fighting cancer: antibodies and Natural Killer T cells (NKT). Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special white 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. 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, investigators made artificial genes called a chimeric antigen receptors (CAR), from an antibody called 14g2a that recognizes GD2, a molecule found on almost all neuroblastoma cells (GD2-CAR). Investigators put these genes into the patients' own T cells and gave them back to patients that had neuroblastoma.
NKT cells are another special subgroup of white blood cells that can specifically go into tumor tissue of neuroblastoma. Inside the tumor, there are other white blood cells called macrophages which help the cancer cells to grow and recover from injury. NKT cells can specifically kill these macrophages and slow the tumor growth.
We will expand NKT cells and add GD2-specific chimeric antigen receptors to the cells. We think these cells might be better able to attack NB since they also work by destroying the macrophages that allows the tumor to grow. The chimeric antigen receptor will also contain a gene segment to make the NKT cells last longer. This gene segment is called CD28. In addition, to further improve the antitumor activity of the GINAKIT cells we added another gene expressing a molecule called Interleukin -15 (IL-15). The combination of these 3 components showed the most antitumor activity by CAR expressing NKT cells and improved these cells' survival in animal models.
GD2-CAR expressing NKTs have not been tested in patients so far. The purpose of this study is to find the largest effective and safe dose of GD2-CAR NKT cells (GINAKIT cells), to evaluate their effect on the tumor and how long they can be detected in the patient's blood and what affect they have on the patient's neuroblastoma.
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma||Genetic: GINAKIT Cells Drug: Cyclophosphamide Drug: Fludarabine||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||GD2 Specific Chimeric Antigen Receptor (CAR) and Interleukin-15 Expressing Autologous Natural Killer T-cells to Treat Children With Neuroblastoma|
|Actual Study Start Date :||January 18, 2018|
|Estimated Primary Completion Date :||September 1, 2021|
|Estimated Study Completion Date :||August 10, 2034|
Experimental: GINAKIT cells + cytoxan + fludara
Cyclophosphamide and fludarabine will be administered prior to the GINAKIT cells.
Day -4: Cyclophosphamide and Fludarabine
Day -3: Cyclophosphamide and Fludarabine
Day -2: Fludarabine
Day -1: Rest
Day 0: GINAKIT cells
Genetic: GINAKIT Cells
Four dose levels of GINAKIT cells will be studied. Dosing will be based on the actual number of transduced cells. All doses are per m2.
Cyclophosphamide (500 mg/m2/day) will be given for 2 days; given on day -4 and day -3 with GINAKIT cells given on day 0.
Other Name: Cytoxan
Fludarabine (30 mg/m2/day) will be given for 3 days; given on day -4, day -3 and day -2 with GINAKIT cells given on day 0.
Other Name: Fludara
- Maximum tolerated dose of autologous NKTs expressing a 2nd generation GD2-specific chimeric antigen receptor administered to patients with relapsed or refractory neuroblastoma. [ Time Frame: 28 days ]Defined as the highest dose level that will have at most a 33% chance of inducing the following NKT-cell-related dose limiting toxicities (DLTs) within 28 days after infusion of NKTs.
- Anti-tumor response of autologous GINAKIT cells in patients with relapsed/refractory neuroblastoma. [ Time Frame: 15 years ]Summarize tumor response by calculating overall response rates and report the Kaplan-Meier curves for the relapse-free survival.
- Immunologic response of autologous GINAKIT cells in patients with relapsed/refractory neuroblastoma. [ Time Frame: 15 years ]Summarize at pre- and post-infusion time points using descriptive statistics to evaluate their expansion and persistence. Changes in each of these NKTs from pre-infusion to each time point of post-infusion will be assessed and compared.
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): NCT03294954
|Contact: Andras Heczey, MDfirstname.lastname@example.org|
|Contact: Josalind Randallemail@example.com|
|United States, Texas|
|Texas Children's Hospital||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Andras Heczey, MD 832-824-4233 firstname.lastname@example.org|
|Principal Investigator:||Andras Heczey, MD||Baylor College of Medicine|