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

NCT03774654 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: H-44526 ANCHORP50CA126752
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Refractory B-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Small Lymphocytic Lymphoma; Relapsed Adult ALL; Relapsed CLL; Relapsed Non Hodgkin Lymphoma

Keywords

Gene Therapy; CAR T-cells; chimeric antigen receptor; B-Cell Malignancies; CD19

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT) rate

  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.

  4 weeks post T cell infusion

Secondary Outcomes (2)

• Frequency of circulating CD19.CAR-aNKT cells transduced with the vector.

  6 weeks post T cell infusion

• 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).

  4-6 weeks post T cell infusion

Study Arms (2)

CD19.CAR-aNKT cells (cohort A, non-ALL)

EXPERIMENTAL

This cohort is for patients without refractory/relapsed B-cell NHL or leukemia (ALL). Three 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

CD19.CAR-aNKT cells (cohort B, ALL).

EXPERIMENTAL

This cohort is for patients with refractory/relapsed B-cell NHL or leukemia (ALL). Three 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

Interventions

CD19.CAR-aNKT cells GENETIC

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.

CD19.CAR-aNKT cells (cohort A, non-ALL); CD19.CAR-aNKT cells (cohort B, ALL).

Eligibility Criteria

• Age: 3 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CD19-positive B-cell lymphoma or leukemia (ALL or CLL).
• The disease is:
• Cohort A (non-ALL patients):
• Relapsed or refractory after two or more lines of therapy, including a CD20 antibody, if an indolent lymphoma.
• Relapsed or refractory after two or more lines of therapy, including ibrutinib and venetoclax, if CLL.
• 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.
• Measurable disease by current criteria (Lugano criteria for lymphomas, IWG criteria for CLL, and detectable disease for ALL).
• Age ≥ 3 and ≤75 years.
• Bilirubin \< 2 times (3 times if Gilbert syndrome) upper limit of normal
• AST and ALT less than 5 times the upper limit of normal.
• Estimated GFR ≥ 50 mL/min.
• Pulse oximetry of ≥ 90% on room air

You may not qualify if:

• Currently receiving any investigational agents or received any cellular therapies within the previous 6 weeks.
• History of hypersensitivity reactions to murine protein-containing products.
• History of grade 2 to 4 graft-versus-host disease (GVHD)
• Pregnant or lactating.
• Active infection with HIV or HTLV.
• Active infection with HBV or HCV.
• Uncontrolled active bacterial, fungal or other viral infection.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Leukemia, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Study Officials

• Carlos Ramos, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 11, 2018
• First Posted: December 13, 2018
• Study Start: June 22, 2020
• Primary Completion (Estimated): June 20, 2026
• Study Completion (Estimated): February 28, 2035
• Last Updated: July 1, 2025

Record last verified: 2025-06

Locations

US (2)