Laboratory-Treated T Cells in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Recurrent or Refractory B-Cell Lymphoma or Multiple Myeloma
- 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 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
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.
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 Phase I
Trial Type Treatment
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Carlos Almeida Ramos
- Primary ID CHARKALL
- Secondary IDs NCI-2012-00845, H-23574, H-23574-CHARKALL
- Clinicaltrials.gov ID NCT00881920