Trivalent CAR-T Cell in Acute B-Lineage Leukemia (TRICAR-ALL)
ConditionLeukemia, B-Cell
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age12-25
SponsorBaylor College of Medicine
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of refractory or recurrent B cell Acute Lymphoblastic Leukemia (B-ALL) with expression of CD19, CD20 and/or CD22
Age between 1 and 25 years.
Life expectancy of ≥ 8 weeks
Weight ≥ 10 kg
Disqualifiers
Active malignancy other than disease under study
Presence of active severe infection, defined as: a) positive blood culture within 48 hours of collection, OR; b) known history of active viral infections including infection with HIV, hepatitis B, hepatitis C or HTLV
Primary immunodeficiency syndrome
Pregnant or breastfeeding
Trial design
Design model
Single group
Treatments tested in this trial
Autologous TRICAR-ALL T-cells and lymphodepletion chemotherapy
GeneticThree dose levels will be evaluated with the opportunity to dose de-escalate (dose level -1) for toxicity. DL-1: 3x10\^6 cells/m2 DL1: 1×10\^7 cells/m2 DL2: 3×10\^7 cells/m2 DL3: 1×10\^8 cells/m2 Lymphodepletion chemotherapy consisting of Fludarabine 30 mg/m2 IV once daily x 4 doses; and Cyclophosphamide 500mg/m2 IV once daily x 2 doses (starting with the first dose of fludarabine)must be completed greater than or equal to 48 hours prior to infusion of CAR-T cells.
Treatment groups
38 Participants
are divided into 1 treatment groupGroup A: Autologous TRICAR-ALL T-Cells and lymphodepletion chemotherapyExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Dose-limiting toxicity (DLT) rate by CTCAE v5.0
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).
Time frame
within 28 days of the TRICAR-ALL T cell infusion.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Baylor College of Medicine
Lead sponsor
Texas Children's Cancer Center
Collaborator
Source ClinicalTrials.gov