C7R-GD2.CART Cells for Patients With Relapsed or Refractory Neuroblastoma and Other GD2 Positive Cancers (GAIL-N)
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|ClinicalTrials.gov Identifier: NCT03635632|
Recruitment Status : Recruiting
First Posted : August 17, 2018
Last Update Posted : January 14, 2020
|First Submitted Date ICMJE||August 13, 2018|
|First Posted Date ICMJE||August 17, 2018|
|Last Update Posted Date||January 14, 2020|
|Actual Study Start Date ICMJE||April 23, 2019|
|Estimated Primary Completion Date||June 2022 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||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.
|Original Primary Outcome Measures ICMJE||Same as current|
|Current Secondary Outcome Measures ICMJE
||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
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||C7R-GD2.CART Cells for Patients With Relapsed or Refractory Neuroblastoma and Other GD2 Positive Cancers (GAIL-N)|
|Official Title ICMJE||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)|
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.
To prepare the T cells (GD2-C7R T cells), research staff will take some blood from the patient. We will grow the GD2.C7R T cells by infecting the T cells with a retroviral vector (a special virus that can carry a new gene into cells) containing one gene that can recognize and kill cancer cells (GD2.CAR) and the new gene called C7R that will help these cells survive longer. After the new genes have been put into the T cells, the cells will be tested to make sure that they kill GD2-positive cancer cells.
Because we are growing the cells in the laboratory, we will also need to take blood to test for infectious viruses such as hepatitis and HIV (the virus that causes AIDS), and we will also ask patients to complete a questionnaire that is given to blood donors.
The cells generated will be frozen and stored to give back to the patient. Because patients will have received cells with a new gene in them patients will be followed for a total of 15 years to see if there are any long term side effects of gene transfer.
Patients will be assigned a dose of GD2-C7R T cells. The assigned dose of cells is based on body weight and height.
In this study, patients will receive the GD2-C7R cells and may also receive cyclophosphamide and fludarabine. These two drugs are standard chemotherapy medicines and may be given before the T cells to make space in the blood for the T cells to grow after receiving them.
If the patient receives cyclophosphamide and fludarabine, these drugs will be given intravenously (through an i.v. needle inserted in a vein or a central line) for 2 days and then fludarabine alone on the third day.
The patient will be given an injection of GD2-C7R T cells into the vein through an IV line at the assigned dose. Before receiving the T cell infusion, the patient may be given a dose of Benadryl (diphenhydramine) and Tylenol (acetaminophen). The infusion will take between 1 and 10 minutes. We will then monitor the patient in the clinic for about 3 hours. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital. The patient may need to stay in Houston for up to 4 weeks after the infusion so we can monitor for side effects.
The patient will have follow-up visits after the T cell infusion at weeks 1, 2, 4, 6, and 8, then at months 3, 6, 9, and 12, and then twice a year for the next 4 years and annually for the next 10 years for a total of 15 years. The patient will also have scheduled disease evaluations after the T-cell injection at week 6 and then as clinically needed.
After disease re-evaluation, if the patient's disease has not gotten worse, or if in the future it seems the patient might benefit AND the patient has not had a severe side effect caused by the infusion of the GD2-C7R T cells, the patient may be eligible to receive one additional dose of their T cells. The dose will be at the same dose level as the first infusion and separated by at least 6 weeks such that we can make sure the patient has no severe side effects between infusions. If the patient receives an additional dose of GD2-C7R T-cells, then they will need to stay in Houston for up to 4 weeks after the infusion as well so we can monitor for side effects.
Medical tests before treatment--
Before being treated, the patient will receive a series of standard medical tests:
Medical tests during and after treatment--
The patient will receive standard medical tests when they are getting the infusions and afterwards:
To learn more about the way the GD2-C7R T cells are working and how long they last in the body, an extra amount of blood will be obtained on the day that chemotherapy starts, the day of the T-cell infusion(s) and at the end of the T-cell infusion(s), 1, 2, 4, 6 and 8 weeks after the T-cell infusion(s) and every 3 months for the 1st year, every 6 months for the next 4 years and annually for the next 10 years. The amount of blood taken will be based on weight with up to a maximum of 60 ml (12 teaspoons) of blood to be obtained at any one time. For children, the total amount of blood drawn will not be more than 3 ml (less than 1 teaspoon) per 1 kg of body weight on any one day. This volume is considered safe, but may be decreased if the patient is anemic (has a low red blood cell count).
During the time points listed above, if the GD2-C7R T cells are found in the patient's blood at a certain amount, an extra 5 ml (about 1 teaspoon) of blood may need to be collected for additional testing.
If the patient has a procedure where tumor samples are obtained, like a repeat bone marrow evaluation or tumor biopsy, we will request a sample to be used for research purposes.
The patient will receive supportive care for any acute or chronic toxicities, including blood components or antibiotics, and other intervention as appropriate.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 1|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms ICMJE||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.
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Estimated Study Completion Date ICMJE||December 2037|
|Estimated Primary Completion Date||June 2022 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Procurement Inclusion Criteria:
Treatment Inclusion Criteria:
Procurement Exclusion Criteria:
Treatment Exclusion Criteria
|Ages ICMJE||1 Year to 74 Years (Child, Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT03635632|
|Other Study ID Numbers ICMJE||H-42207 GAIL-N|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Bilal Omer, Baylor College of Medicine|
|Study Sponsor ICMJE||Baylor College of Medicine|
|PRS Account||Baylor College of Medicine|
|Verification Date||January 2020|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP