Recruiting
Phase 1

CD19-Specific CAR

Sponsor:

Baylor College of Medicine

Code:

NCT01853631

Conditions

Non-Hodgkin Lymphoma

Chronic Lymphocytic Leukemia

Acute Lymphocytic Leukemia

Eligibility Criteria

Sex: All

Age: 0 - 70+

Healthy Volunteers: Not accepted

Interventions

Dose Escalation Phase:CD19.CAR/28 and CD19.CAR/28137 T cells

Expansion Phase: CD19.CAR/28 and CD19.CAR/28137 T cells

Study Details

Brief summary:

Subjects on this study have a type of lymph gland cancer called Non-Hodgkin Lymphoma, acute lymphocytic leukemia, or chronic Lymphocytic Leukemia (these diseases will be referred to as "lymphoma" or "leukemia"). The lymphoma or leukemia has come back or has not gone away after treatment.

The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and T cells, hoping that they will work together. Both antibodies and T cells have been used to treat patients with cancer. They have shown promise, but have not been strong enough to cure most patients.

T cells can kill tumor cells but normally there are not enough of them to kill all the tumor 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 is called anti-CD19. It first came from mice that have developed immunity to human lymphoma. This antibody sticks to lymphoma cells because of a substance on the outside of these cells called CD19. CD19 antibodies have been used to treat people with lymphoma and leukemia. For this study, anti-CD19 has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor.

In the laboratory, the investigators found that T cells work better if they also add proteins that stimulate T cells, such as one called CD28. Adding the CD28 makes the cells last longer in the body but not long enough for them to be able to kill the lymphoma cells. The investigators believe that if they add an extra stimulating protein, called CD137, the cells will have a better chance of killing the lymphoma cells.

The investigators are going to see if this is true by putting the CD19 chimeric receptor with CD28 alone into half of the cells and the CD19 chimeric receptor with CD28 and CD137 into the other half of the cells. These CD19 chimeric receptor T cells with CD28 and with or without CD137 are investigational products not approved by the FDA.

The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to see how long the T cell with each sort of chimeric receptor lasts, to learn what the side effects are and to see whether this therapy might help people with lymphoma or leukemia.

Conditions

Non-Hodgkin Lymphoma

Chronic Lymphocytic Leukemia

Acute Lymphocytic Leukemia

Study ID

NCT01853631

Start date

Feb, 2014

Status verified date

Dec, 2025

Completion date

Feb, 2036

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

PROCUREMENT

Referred patients (or respective donors) will initially be consented for procurement of blood for generation of the transduced ATL. Eligibility criteria at this stage include:

  • Diagnosis of recurrent B-cell lymphoma or leukemia (ALL or CLL), or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory aggressive B-cell lymphoma with a treatment plan that will include high dose therapy and autologous stem cell transplantation.
  • CD19-positive tumor (result can be pending at this time).
  • Age <= 75 years. The first 3 patients treated on the study should be adults (>= 18 years).
  • Hgb greater than or equal to 7.0 (can be a transfused value)
  • If pheresis required to collect blood:
  • Creatinine < 1.5 x upper limit normal
  • AST <1.5 × upper limit normal
  • PT and APTT <1.5 × upper limit normal
  • Informed consent explained to, understood by and signed by patient/guardian (and donor, where applicable). Patient/guardian given copy of informed consent.

TREATMENT

  • Diagnosis of recurrent B-cell lymphoma leukemia (ALL or CLL), or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory aggressive B-cell lymphoma with a treatment plan that will include high dose therapy and autologous stem cell transplantation.
  • CD19-positive tumor.
  • Age <= 75 years. The first 3 patients treated on the study should be adults (>= 18 years).
  • Bilirubin less than 3 times the upper limit of normal.
  • AST less than 5 times the upper limit of normal.
  • Estimated GFR > 50 mL/min
  • Pulse oximetry of > 90% on room air
  • Karnofsky or Lansky score of > 60%.
  • Recovered from acute toxic effects of prior chemotherapy at least one week before entering this study. PD1/PDL1 inhibitors will be allowed if medically indicated.
  • Available autologous or syngeneic activated peripheral blood T cell products (CD28ζ and CD28/CD137ζ) with more than or equal to 15% expression of CD19.CAR determined by flow cytometry.
  • Life expectancy of greater than 12 weeks.
  • 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.
  • Patients or legal guardians 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.

Exclusion Criteria:

PROCUREMENT

  • Active infection requiring antibiotics.
  • No history of other cancer (except non-melanoma skin cancer or in situ breast cancer or cervix cancer) unless the tumor was successfully treated with curative intent at least 2 years before trial entry.

TREATMENT

  • Currently receiving any investigational agents or received any tumor vaccines within the previous 6 weeks. (Note treatment with PD1/PDL1 inhibitors is allowed.)
  • History of hypersensitivity reactions to murine protein-containing products.
  • Pregnant or lactating.
  • Tumor in a location where enlargement could cause airway obstruction.
  • Active infection with HIV or HTLV.

Study Design

Enrollment

64 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose Escalation: CD19 CAR T Cells for B-cell ALL

Each patient will receive a dose of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.

experimental: Dose Expansion: CD19 CAR T Cells for B-cell ALL

Each patient will receive the maximum tolerated dose (MTD) of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.

experimental: Dose Escalation: CD19 CAR T Cells for B-cell NHL/CLL

Each patient will receive a dose of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.

experimental: Dose Expansion: CD19 CAR T Cells for B-cell NHL/CLL

Each patient will receive the maximum tolerated dose (MTD) of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.

Interventions

Dose Escalation Phase:CD19.CAR/28 and CD19.CAR/28137 T cells

Three dose levels will be evaluated.

Group 1: CD19.CAR/28137ζ at 1×10\^6 cells/m\^2 and CD19.CAR/28ζ at 1×10\^6 cells/m\^2

Group 2: CD19.CAR/28137ζ at 5×10\^6 cells/m\^2 and CD19.CAR/28ζ at 5×10\^6 cells/m\^2

Group 3: CD19.CAR/28137ζ at 2×10\^7 cells/m\^2 and CD19.CAR/28ζ at 2×10\^7 cells/m\^2

Expansion Phase: CD19.CAR/28 and CD19.CAR/28137 T cells

The primary goal of the expanded cohort is to further study the safety profiles of CAR-T cells in each of the disease settings, both with or without lymphodepleting chemotherapy given before CAR-T cell infusion.

Primary outcome measure

  • Number of patients with dose limiting toxicity (DLT) [ Time Frame: 6 weeks ]

Central Contacts and Locations

Central contacts

Carlos A Ramos, MD

832-824-4817caramos@bcm.edu

Mahshid Azamian

832-512-0690Mahshid.Azamian@bcm.edu

Locations

Houston Methodist Hospital

Recruiting

Houston, Texas, United States, 77030

Contacts

Carlos A. Ramos, MD

832-824-4817caramos@bcm.edu

Mahshid Azamian

832-512-0690Mahshid.Azamian@bcm.edu

Texas Children's Hospital

Recruiting

Houston, Texas, United States, 77030

Contacts

Carlos A. Ramos, MD

832-824-4817caramos@bcm.edu

Mahshid Azamian

832-512-0690Mahshid.Azamian@bcm.edu

More Information

Sponsor

Baylor College of Medicine

Last update posted

Jan 5, 2026

Last verified

Dec, 2025

Keywords

  • chronic Lymphocytic Leukemia
  • refractory
  • recurrent
  • aggressive B-cell Lymphoma
  • CD19
  • Non-Hodgkin Lymphoma
  • CD28
  • CD137
  • 4-1BB
  • acute lymphocytic leukemia

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Baylor College of Medicine on 2026-01-05.