Using modified T-cells to treat advanced B-cell cancers

Phase I Study of Activated T-Cells Expressing Second or Third Generation CD19-Specific Chimeric Antigen Receptors for Advanced B-Cell Non-Hodgkin's Lymphoma, Acute Lymphocytic Leukemia and Chronic Lymphocytic Leukemia (SAGAN)

This study is testing whether modified T-cells can help patients with advanced B-cell cancers that haven't responded to other treatments by boosting their immune system to fight the cancer better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 64 (estimated)
• Ages: N/A to 75 Years
• Sex: All
• Sponsor: Baylor College of Medicine (Academic / other)
• Drugs / interventions: chemotherapy, cyclophosphamide, fludarabine, Cytoxan
• Locations: 2 sites (Houston, Texas and 1 other locations)
• Trial ID: NCT01853631 on ClinicalTrials.gov

What this trial studies

This clinical trial focuses on patients with advanced B-cell cancers, including Non-Hodgkin Lymphoma, Acute Lymphocytic Leukemia, and Chronic Lymphocytic Leukemia, who have not responded to previous treatments. The study involves extracting T-cells from the patient's blood, modifying them in the laboratory to express a CD19-specific chimeric antigen receptor (CAR), and then reintroducing these enhanced T-cells back into the patient. The goal is to improve the ability of the immune system to target and destroy cancer cells. Patients will be monitored for long-term effects of this gene therapy approach.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 75 with recurrent or refractory B-cell lymphoma or leukemia that express the CD19 antigen.

Not a fit: Patients with non-CD19-positive tumors or those who are not eligible for high-dose therapy and autologous stem cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new, effective option for patients with aggressive B-cell cancers that have not responded to standard therapies.

How similar studies have performed: Other studies using CAR T-cell therapy have shown promising results, indicating that this approach has potential for success.

Eligibility criteria

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.

Where this trial is running

Houston, Texas and 1 other locations

• Houston Methodist Hospital — Houston, Texas, United States (Recruiting)
• Texas Children's Hospital — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Carlos A Ramos, MD — Baylor College of Medicine
• Study coordinator: Carlos A Ramos, MD

Conditions Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Acute Lymphocytic Leukemia; chronic Lymphocytic Leukemia; refractory; recurrent; aggressive B-cell Lymphoma; CD19