Gene therapy using Kappa-CD28 T cells for certain blood cancers

Phase I Study of Adoptive Transfer of Autologous T Lymphocytes Engrafted with a Chimeric Antigen Receptor Targeting the Kappa Light Chain of Immunoglobulin Expressed in Patients with CLL, B-Cell Lymphoma or Multiple Myeloma

This study is testing a new gene therapy using modified T cells to see if it can help people with certain blood cancers like chronic lymphocytic leukemia and multiple myeloma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Baylor College of Medicine (Academic / other)
• Drugs / interventions: Rituximab, chemotherapy, cyclophosphamide, fludarabine
• Locations: 2 sites (Houston, Texas and 1 other locations)
• Trial ID: NCT00881920 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates a novel gene transfer approach using Kappa-CD28 T lymphocytes to treat patients with recurrent or refractory B-cell malignancies, including chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). The study involves collecting blood from patients to modify T cells with a retrovirus that introduces a specific antibody gene, enhancing their ability to target and destroy cancer cells. Patients may receive pre-treatment with cyclophosphamide and fludarabine to reduce their existing T cell population, allowing the infused T cells to proliferate effectively. Participants will be monitored for long-term effects of this gene therapy over a period of 15 years.

Who should consider this trial

Good fit: Ideal candidates include individuals with B-CLL, recurrent or refractory B-cell lymphoma, or multiple myeloma who have a life expectancy of at least 12 weeks.

Not a fit: Patients with a history of other cancers (except certain non-melanoma skin cancers) or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients with difficult-to-treat blood cancers.

How similar studies have performed: Other studies utilizing similar gene therapy approaches have shown promise, indicating potential for success in this novel application.

Eligibility criteria

INCLUSION CRITERIA:

BLOOD PROCUREMENT:

* B-CLL or recurrent or refractory B-cell lymphoma (or other B-cell neoplasm) or multiple myeloma monoclonal for Kappa-light chain
* Life expectancy of at least 12 weeks or greater.
* 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
* If requires pheresis to collect blood, Cre and AST less than 1.5 upper limit of normal
* If requires pheresis to collect blood, PT and PTTK less than 1.5 upper limit normal

T CELL TREATMENT:

Diagnosis of:

1. B-CLL monoclonal for Kappa light chain with one of the following criteria:

   1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
   2. Massive (ie, at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly
   3. Massive nodes (ie, at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
   4. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months.
   5. Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs:

      1. Unintentional weight loss of 10% or more within the previous 6 months;
      2. Significant fatigue (ie, ECOG PS 2 or worse; inability to work or perform usual activities);
      3. Fevers higher than 100.5°F or 38.0°C for 2 or more weeks without other evidence of infection; or
      4. Night sweats for more than 1 month without evidence of infection.
      5. Patients who have resistant disease after primary treatment
      6. Patients who have a short time to progression after the first treatment (less than 2 years)

   OR
2. Indolent or aggressive B-cell lymphoma (or other B-cell neoplasm) monoclonal for Kappa-light chain with measurable disease after receiving at least one chemotherapy regimen that includes Rituximab or an equivalent monoclonal antibody

   OR
3. Multiple myeloma monoclonal for Kappa-light chain with measurable disease after receiving at least one chemotherapy regimen

   * Life expectancy of at least 12 weeks or greater.
   * Recovered from the toxic effects of all prior chemotherapy before entering this study. PD1/PDL1 inhibitors will be allowed if medically indicated
   * ANC \> 500, Hgb greater than or equal to 7.0.
   * Bilirubin less than 3 times the upper limit of normal.
   * AST less than 5 times the upper limit of normal.
   * Estimated GFR \> 50mL/min
   * Pulse oximetry of \> 90% on room air
   * Karnofsky score of \> 60%.
   * Negative serology for HIV.
   * Available autologous transduced peripheral blood T-cells with 15% or more expression of CAR-Kappa determined by flow-cytometry.
   * 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 will be given a copy of the consent form.
   * Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 3 months after the study is concluded. The male partner should use a condom.
   * If patient has CLL, must have negative Coombs test.

EXCLUSION CRITERIA:

BLOOD PROCUREMENT:

* Active infection requiring antibiotics
* Active autoimmune disease

T CELL TREATMENT:

* Symptomatic cardiac disease.
* History of hypersensitivity reactions to murine protein-containing products. Currently receiving any investigational agents within the previous six weeks or received any tumor vaccines within the previous 6 weeks.
* Tumor in a location where enlargement could cause airway obstruction.
* Pregnant or lactating.

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 Ramos, MD — Baylor College of Medicine - Texas Children's Hospital
• Study coordinator: Carlos Ramos, MD

Conditions Lymphoma; Myeloma; Leukemia; Lymphocytic; B Cell; Non-Hodgkin; Multiple Myeloma