CD19.CAR Allogeneic NKT for Patients With Relapsed or Refractory B-Cell Malignancies (ANCHOR)
|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: NCT03774654|
Recruitment Status : Not yet recruiting
First Posted : December 13, 2018
Last Update Posted : April 15, 2020
This study is for patients who have lymphoma or leukemia that has come back or has not gone away after treatment. Because there is no standard treatment for this cancer, patients are being asked to volunteer for a gene transfer research study using special immune cells.
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 disease, antibodies and immune cells. Antibodies are types of proteins that protect the body from bacteria and other diseases. Immune cells, also called lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. Both antibodies and lymphocytes have been used to treat patients with cancer. They have shown promise, but have not been strong enough to cure most patients.
The antibody used in this study is called anti-CD19. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD19. CD19 antibodies have been used to treat people with lymphoma and leukemia. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood it is now joined to the NKT cells, a special type of lymphocytes that can kill tumor cells but not very effectively on their own. When an antibody is joined to a T cell in this way it is called a chimeric receptor. Investigators have also found that NKT cells work better if proteins are added that stimulate lymphocytes, such as one called CD28. Adding the CD28 makes the cells last for a longer time in the body but maybe not long enough for them to be able to kill the lymphoma cells. It is believed that by adding an extra stimulating protein, called IL-15, the cells will have an even better chance of killing the lymphoma cells.
In this study the investigators are going to see if this is true by putting the anti-CD19 chimeric receptor with CD28 and the IL-15 into NKT cells grown from a healthy individual. These cells are called ANCHOR cells. These cells will be infused into patients that have lymphomas or leukemias that have CD19 on their surface. The ANCHOR cells are investigational products not approved by the Food and Drug Administration.
The purpose of this study is to find the biggest dose of ANCHOR cells that is safe, to see how long the ANCHOR cells last, to learn what their side effects are and to see whether this therapy might help people with lymphoma or leukemia.
|Condition or disease||Intervention/treatment||Phase|
|Refractory B-Cell Non-Hodgkin Lymphoma Refractory B-Cell Small Lymphocytic Lymphoma Relapsed Adult ALL Relapsed CLL Relapsed Non Hodgkin Lymphoma||Genetic: CD19.CAR-aNKT cells Drug: Cyclophosphamide Drug: Fludarabine||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Allogeneic Natural Killer T-Cells Expressing CD19 Specific Chimeric Antigen Receptor and Interleukin-15 in Relapsed or Refractory B-Cell Malignancies|
|Estimated Study Start Date :||April 2020|
|Estimated Primary Completion Date :||April 2023|
|Estimated Study Completion Date :||March 2035|
Experimental: CD19.CAR-aNKT cells
This is a single arm study. Four dose levels will be evaluated. Patients will also receive lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine followed by the CD19.CAR-aNKT cell infusion.
Genetic: CD19.CAR-aNKT cells
Patients will be given the T-cell product by intravenous injection (into the vein through an IV line) at the assigned dose.
Dose Level 1: 1 x 10^7/m2. Dose Level 2: 3 x 10^7/m2. Dose Level 3: 1 x 10^8/m2. Dose Level 4: 3 x 10^8/m2.
Lymphodepletion chemotherapy. Patients will receive 3 daily doses of cyclophosphamide (500mg/m^2/day) finishing at least 24 hours before T-cell infusion. The drug will be given intravenously (through an IV needle).
Other Name: Cytoxan
Lymphodepletion chemotherapy. Patients will receive 3 daily doses of fludarabine (30mg/m^2/day) finishing at least 24 hours before T-cell infusion. The drug will be given intravenously (through an IV needle).
Other Name: Fludara
- Dose limiting toxicity (DLT) rate [ Time Frame: 4 weeks post T cell infusion ]DLT rate is defined as the proportion of subjects with DLT evaluated as per the NCI CTCAE v5.0 with the exception of CRS and neurological toxicities that are related to T-cell infusions. GVHD will be graded according to the BMT CTN Technical Manual of Procedures v3.0.
- Frequency of circulating CD19.CAR-aNKT cells transduced with the vector. [ Time Frame: 6 weeks post T cell infusion ]The frequency of the infused cells will be summarized at pre- and post-infusion time points to evaluate their expansion and persistence.
- Overall response rate according to the Lugano criteria for non-Hodgkin lymphomas (for NHL) and the IWG (for CLL), or the proportion of patients with morphologic CR (for ALL). [ Time Frame: 4-6 weeks post T cell infusion ]Overall response rate is defined as the proportion of subjects with best overall response of complete response (CR) or partial response (PR) according to the Lugano criteria for non-Hodgkin lymphomas (for NHL) and the IWG (for CLL), or the proportion of patients with morphologic CR (for ALL).
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): NCT03774654
|Contact: Carlos Ramos, MD||(832) email@example.com|
|Contact: Anaid Reyes||832-824-3855||Anaid.Reyes@bcm.edu|
|Principal Investigator:||Carlos Ramos, MD||Baylor College of Medicine|