Kappa-CD28 T Lymphocytes, Chronic Lymphocytic Leukemia, B-cell Lymphoma or Multiple Myeloma, CHARKALL (CHARKALL)
Lymphoma, Myeloma, Leukemia
About this trial
This is an interventional treatment trial for Lymphoma focused on measuring Lymphocytic, Leukemia, B Cell, Non-Hodgkin, Multiple Myeloma, Lymphoma
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:
B-CLL monoclonal for Kappa light chain with one of the following criteria:
- Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
- Massive (ie, at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly
- Massive nodes (ie, 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 (ie, ECOG 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 (less than 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. 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.
Sites / Locations
- Houston Methodist HospitalRecruiting
- Texas Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Kappa CD28 T cells for B-CLL
Kappa CD28 T cells for B-cell lymphoma
Kappa CD28 T cells for myeloma
T cells will be infused at least 24 hours after chemotherapy. Three dose levels will be evaluated. Cohorts of size 2 will be enrolled at each dose level. Each patient will receive one injection 2-30 mL of each dose over 1 to 20 minutes.
T cells will be infused at least 24 hours after chemotherapy. Three dose levels will be evaluated. Cohorts of size 2 will be enrolled at each dose level. Each patient will receive one injection 2-30 mL of each dose over 1 to 20 minutes.
T cells will be infused at least 24 hours after chemotherapy. Three dose levels will be evaluated. Cohorts of size 2 will be enrolled at each dose level. Each patient will receive one injection 2-30 mL of each dose over 1 to 20 minutes.