CD19.CAR Allogeneic NKT for Patients With Relapsed or Refractory B-Cell Malignancies (ANCHOR)

• Status: Recruiting
• Trial end date: 2035-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborators: Center for Cell and Gene Therapy, Baylor College of Medicine; Texas Children's Hospital; The Methodist Hospital Research Institute; The Methodist Hospital System
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate

Criteria

Treatment Inclusion Criteria:

1. Diagnosis of CD19-positive B-cell lymphoma or leukemia (ALL or CLL).

2. The disease is:

Cohort A (non-ALL patients):

1. Relapsed or refractory after two or more lines of therapy, including a CD20 antibody, if an indolent lymphoma.

2. Relapsed or refractory after two or more lines of therapy, including ibrutinib and venetoclax, if CLL.

3. Relapsed or refractory after two or more lines of therapy, including a CD20 antibody and an anthracycline, and the patient is ineligible for autologous stem cell transplantation, if an aggressive or highly aggressive lymphoma.

• Ineligibility for autologous stem cell transplantation includes non-responsive disease after salvage therapy and failure to mobilize stem cells for transplant.

Cohort B (ALL patients)

a. Relapsed or refractory after two or more lines of therapy, if ALL.

3. Measurable disease by current criteria (Lugano criteria for lymphomas, IWG criteria for CLL, and detectable disease for ALL).

4. Age ≥ 3 and ≤75 years.

5. Bilirubin < 2 times (3 times if Gilbert syndrome) upper limit of normal

6. AST and ALT less than 5 times the upper limit of normal.

7. Estimated GFR ≥ 50 mL/min.

8. Pulse oximetry of ≥ 90% on room air

9. Karnofsky or Lansky score of ≥ 70.

10. Recovered from the acute toxic effects of all prior chemotherapy based on the enrolling physician's assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria).

11. Life expectancy of greater than 12 weeks.

12. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.

13. Patients must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form.

Treatment Exclusion Criteria:

1. Currently receiving any investigational agents or received any cellular therapies within the previous 6 weeks.

2. History of hypersensitivity reactions to murine protein-containing products.

3. Pregnant or lactating.

4. Active infection with HIV or HTLV.

5. Active infection with HBV or HCV.

6. Uncontrolled active bacterial, fungal or other viral infection.