Genetically Modified T-Cells in Treating Patients With Advanced Non-Hodgkin's Lymphoma

Status: Active

Description

This phase I trial studies the side effects and the best dose of genetically modified T-cells in treating patients with advanced non-Hodgkin's lymphoma. Biological therapies, such as genetically modified T-cells may stimulate or suppress the immune system in different ways and stop cancer cells from growing.

Eligibility Criteria

Inclusion Criteria

  • PROCUREMENT INCLUSION CRITERIA * Diagnosis of recurrent aggressive or indolent B-cell lymphoma 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) * Hemoglobin (Hgb) > 8.0 * If pheresis required to collect blood: ** Creatinine < 1.5 × upper limit normal ** Aspartate aminotransferase (AST) < 1.5 × upper limit normal ** Prothrombin time (PT) and activated partial thromboplastin time (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 INCLUSION CRITERIA:
  • Diagnosis of recurrent aggressive or indolent B-cell lymphoma 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
  • Absolute neutrophil count (ANC) > 500
  • Hgb > 8.0
  • Bilirubin less than 3 times the upper limit of normal
  • AST less than 5 times the upper limit of normal
  • Serum creatinine less than 3 times the upper limit of normal
  • 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
  • Available autologous or syngeneic activated peripheral blood T cell products (CD28zeta and CD28/CD137zeta) with >= 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 EXCLUSION CRITERA * 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 EXCLUSION CRITERIA:
  • Currently receiving any investigational agents or received any tumor vaccines within the previous 6 weeks
  • 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 human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV)

Locations & Contacts

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Carlos Almeida Ramos
Phone: 713-790-2700
Email: caramos@bcm.edu
Center for Cell and Gene Therapy
Status: Active
Contact: Carlos Almeida Ramos
Phone: 713-790-2700
Email: caramos@bcm.edu
Texas Children's Hospital
Status: Active
Contact: Carlos Almeida Ramos
Phone: 713-790-2700
Email: caramos@bcm.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the safety of escalating doses of autologous or syngeneic activated peripheral blood T lymphocytes (ATLs) genetically modified to express artificial T-cell receptors (chimeric antigen receptors or CAR) targeting the cluster of differentiation (CD) 19 molecule (CD19.CAR) and incorporating two costimulatory domains (CD28+CD137), in patients with refractory/relapsed indolent and aggressive B-cell non-Hodgkin lymphomas (NHL), including chronic lymphocytic leukemia (CLL). These will be given together with an equal dose of ATLs genetically modified to express a CAR targeting the same CD19 molecule but incorporating a single costimulatory domain (CD28).

SECONDARY OBJECTIVES:

I. To measure the survival and function of CD19.CAR-ATLs in vivo.

II. To compare two different T-cell products in the same patient in which the CD19.CAR will differ only by the inclusion of the CD137 co-stimulatory endodomain.

III. To measure the anti-tumor effects of CD19.CAR-ATLs in patients with indolent or aggressive NHL or CLL.

IV. To discover if the clinical and laboratory data collected following additional doses of cells are consistent with a cumulative rise in the percentage of circulating gene modified cells and if the infusions are associated with sequential reductions in patient disease burden.

OUTLINE: This is a dose-escalation study.

Patients receive autologous or syngeneic ATLs genetically modified to express CD19.CAR/28137zeta intravenously (IV) over 1-10 minutes and CD19.CAR/28zeta IV over 1-10 minutes.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months; every 6 months for 4 years; and then annually for 10 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Carlos Almeida Ramos

Trial IDs

Primary ID H-31970
Secondary IDs NCI-2013-01017, H-31970 SAGAN, SAGAN
Clinicaltrials.gov ID NCT01853631