Trivalent CAR-T Cell in Acute B-Lineage Leukemia (TRICAR-ALL)
- Conditions
- Leukemia, B-Cell
- Interventions
- Genetic: Autologous TRICAR-ALL T-cells and lymphodepletion chemotherapy
- Registration Number
- NCT05010564
- Lead Sponsor
- Baylor College of Medicine
- Brief Summary
This is a gene transfer study for patients with a type of blood cancer called Acute Lymphoblastic Leukemia (ALL) that has come back or has not gone away after treatment.
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. 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. They have shown promise but have not been strong enough to cure most patients. For example, T lymphocytes can kill cancer cells but there normally are not enough of them to kill all the cancer cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person.
The antibody used in this study targets CD19, CD20 and CD22. This antibody sticks to ALL cells because of a substance on the outside of these cells called CD19, CD20 and/or CD22. For this study, the antibody to CD19, CD20 and CD22 has been changed so that instead of floating free in the blood, it is now joined to the T cells. When T-cells contain an antibody that is joined to them, they are called chimeric antigen receptor- T cells or CAR-T cells.
In the laboratory, we have also found that T cells work better if we also add proteins that stimulate them. One such protein is called 4-1BB. Adding the 4-1BB molecule makes the cells grow better and last longer in the body, giving them a better chance of killing the leukemia cells. In this study we are going to attach the CD19/CD20/CD22 chimeric receptor that has 4-1BB added to the patient's T cells. We will then test how long the cells last.
These T cells, called "TRICAR-ALL" T cells are investigational products not approved by the Food and Drug Administration (FDA) outside the context of a clinical trial.
- Detailed Description
The TRICAR-ALL T-cells were made in the laboratory by stimulating the patient's blood with growth factors to make the T cells grow. To get the CD19/CD20/CD22 antibody and 4-1BB to attach to the surface of the T cell, we inserted the antibody gene into the T cell. This is done using a virus called a retrovirus that has been made for this study and will carry the antibody gene into the T cell.
Enrolled patients will be assigned a dose of TRICAR-ALL T-cells. Prior to receiving the TRICAR-ALL T-cells patients will receive two chemotherapy medications, cyclophosphamide (for 2 days) and fludarabine (4 days).
An injection of TRICAR-ALL T-cells will be given into a vein through an IV at the assigned dose. The injection will take from 1 to 20 minutes. Before receiving the infusion of TRICAR-ALL T-cells patients may be pre-medicated with diphenhydramine (Benadryl) and acetaminophen (Tylenol). Patients will be monitored for up to 3 hours after the injection, and will have to remain locally for at least 4 weeks.
If after a 4-week evaluation period, the patient has a complete response, they may proceed to bone marrow transplant, and will be removed from the treatment portion of the study.
Before treatment, patients will undergo a series of tests:
* Physical exam and History
* Blood tests to measure blood cells, serum chemistry, kidney and liver function
* Testing for viral exposures and/ infections
* Pregnancy test for female patients who are of childbearing potential
* Measurements of your leukemia tumor cells by bone marrow studies and spinal tap.
* Echocardiogram
* Imaging such as PET scans, CT scans or MRIs will be obtained if needed
During and after treatment, patients will receive these standard medical tests:
* History and physical examination: pre-infusion of T cells (pre-Day 0), infusion day (Day 0) and on Days 1-, 4-, 7-, 10-, weeks 2-, 4-, 6-, and 8 post infusion of T- cells. Subsequently, history will be taken at 3-, 6-, 9- and 12-months post infusion of T-cells, and then yearly for a total of 15 years.
* Blood tests to measure blood cells, serum chemistry, kidney and liver function: pre-infusion of T cells (pre-Day 0), infusion day (Day 0) and on Days 4, 7, 10, weeks 2-, 4-, and 8; then at month 3, 6, and 12; then yearly to year 15.
* Viral PCRs: pre-infusion of T cells (pre-Day 0), infusion day (Day 0), weeks 1-, 2-, 4- and 8; then at month 3, 6, 9 and 12.
* Measurements of your leukemia tumor cells by bone marrow studies at week 4 (+/- 3 days) and week 8 (+/- 3 days) after the infusion and then per standard of care.
* Imaging such as PET scans, CT scans or MRIs will be obtained, if needed, 4-8 weeks following the infusion
Blood Draws:
Blood will be taken before the chemotherapy drugs, 2-4 hours after the T cell infusion, and on Days 4, 7, 10, weeks 2-, 4-, and 8 after the infusion; then at month 3, 6, and 12; then yearly to year 15.
In the event of your death, we will request permission from your next of kin to perform an autopsy to learn more about the effect of this experimental treatment on your cancer.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 38
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Autologous TRICAR-ALL T-Cells and lymphodepletion chemotherapy Autologous TRICAR-ALL T-cells and lymphodepletion chemotherapy Three dose levels will be evaluated. The TRICAR-ALL T-cells will be administered after lymphodepletion chemotherapy with Cyclophosphamide and fludarabine.
- Primary Outcome Measures
Name Time Method Dose-limiting toxicity (DLT) rate by CTCAE v5.0 within 28 days of the TRICAR-ALL T cell infusion. Toxicity for all patients will be evaluated using the NCI common toxicity criteria scale, version 5.0 (https://ctep.cancer.gov) with the exception of CRS and neurological toxicities which will be evaluated based on the ASTCT Consensus Guidelines (Lee et al, BBMT 2019).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Texas Children's Hospital
🇺🇸Houston, Texas, United States