Laboratory-Treated T Cells in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Recurrent or Refractory B-Cell Lymphoma or Multiple Myeloma

Status: Active

Description

This phase I trial studies the side effects of laboratory-treated T cells in treating patients with B-cell chronic lymphocytic leukemia, B-cell lymphoma, or multiple myeloma that has come back or has not gone away after treatment. This study combines two different ways of fighting disease, antibodies (proteins that protect the body from bacterial and other diseases) and T cells (special infection-fighting blood cells that can kill other cells, including cancer cells). Treating the T cells in the laboratory by adding an antibody may help the T cells last longer in the body and kill more cancer cells.

Eligibility Criteria

Inclusion Criteria

  • INCLUSION CRITERIA FOR 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, creatinine (Cre) < 1.5 upper limit of normal
  • If requires pheresis to collect blood, aspartate aminotransferase (AST) < 1.5 upper limit of normal
  • If requires pheresis to collect blood, prothrombin time (PT) < 1.5 upper limit normal
  • If requires pheresis to collect blood, partial thromboplastin time (kaolin) (PTTK) < 1.5 upper limit normal
  • INCLUSION CRITERIA FOR T CELL TREATMENT:
  • Diagnosis of: * B-CLL monoclonal for Kappa light chain with one or more of the following criteria: ** Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia ** Massive (i.e., at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly ** Massive nodes (i.e., at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy ** Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months ** Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs: *** Unintentional weight loss of 10% or more within the previous 6 months; *** Significant fatigue (i.e., Eastern Cooperative Oncology Criteria [ECOG] performance status [PS] 2 or worse; inability to work or perform usual activities); *** Fevers higher than 100.5°F or 38.0°C for 2 or more weeks without other evidence of infection; or *** Night sweats for more than 1 month without evidence of infection *** Patients who have resistant disease after primary treatment *** Patients who have a short time to progression after the first treatment (< 2 years) OR * 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 * 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
  • Absolute neutrophil count (ANC) > 500
  • Hemoglobin (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 upper limit of normal
  • Pulse oximetry of > 90% on room air
  • Karnofsky score of > 60%
  • Negative serology for human immunodeficiency virus (HIV)
  • Available autologous transduced peripheral blood T-cells with >= 15% 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 a negative Coombs test

Exclusion Criteria

  • EXCLUSION CRITERIA FOR BLOOD PROCUREMENT:
  • Active infection requiring antibiotics
  • Active autoimmune disease
  • EXCLUSION CRITERIA FOR 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

Locations & Contacts

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Carlos Almeida Ramos
Phone: 832-824-4817
Email: caramos@bcm.edu
Center for Cell and Gene Therapy
Status: Active
Contact: Carlos Almeida Ramos
Phone: 832-824-4817
Email: caramos@bcm.edu
Texas Children's Hospital
Status: Active
Contact: Carlos Almeida Ramos
Phone: 832-824-4817
Email: caramos@bcm.edu
The Methodist Hospital System
Status: Active
Contact: Carlos Almeida Ramos
Phone: 832-824-4817
Email: caramos@bcm.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the safety of autologous T-lymphocytes genetically modified to express chimeric antigen receptors (CAR) targeting the kappa-light chain of human immunoglobulin (CAR-K) in patients with chronic lymphocytic leukemia (B-CLL), B-cell non-Hodgkin Lymphoma (B-NHL) or other B-cell neoplasm, and multiple myeloma (MM) whose tumors express the Kappa-light chain.

SECONDARY OBJECTIVES:

I. To measure the survival and function of CAR-K+ T cells in vivo.

II. To evaluate the impact of T cell infusions on B lymphocyte compartment and humoral immunity.

III. To measure the anti-tumor effects of CAR-K+ T lymphocytes.

OUTLINE: This is a dose-escalation study.

Patients receive autologous CAR-kappa T-cells intravenously (IV) over 1-10 minutes at least 4 days after finishing their current course of chemotherapy or 14-60 days after date of transplant. At the discretion of the attending physician, patients achieving clinical benefit may receive repeat infusions separated by 4-6 weeks. Some patients may also receive cyclophosphamide IV 4-7 days prior to T cell infusion.

After completion of study treatment, patients are followed up every 3 months for 1 year, 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 CHARKALL
Secondary IDs NCI-2012-00845, H-23574-CHARKALL, H-23574
Clinicaltrials.gov ID NCT00881920