INCLUSION CRITERIA:
a. Patient must have a CD19-expressing B cell malignancy of any type. Patients with CLL, mantle cell lymphoma, and follicular lymphoma must have progressive disease after at least one standard chemotherapy regimen. Patients with large cell lymphoma must have progressive disease after at least two prior chemotherapy regimens, one of which must have contained doxorubicin and rituximab. Patients with ALL must have relapsed or refractory disease after at least one standard chemotherapy and one salvage regimen. All patients enrolled on this trial must be deemed incurable by standard therapies. CD19 expression must be detected on greater than 50% of the malignant cells of each patient by immunohistochemistry or flow cytometry.
b. CD19 expression must be detected on greater than 50% of the malignant cells by immunohistochemistry or by flow cytometry in a CLIA approved test in the Laboratory of Pathology, CCR, NCI, NIH. Definition of which cells are malignant must be determined for each patient by the Laboratory of Pathology using techniques to demonstrate monoclonality such as kappa/lambda restriction (other techniques can be used to determine monoclonality at the discretion of the Laboratory of Pathology). The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each patient. Immunohistochemistry will be used for lymph node biopsies; flow cytometry will be used for peripheral blood, fine needle aspirates and bone marrow samples.
c. Patients must have indications for treatment for their B cell malignancy at the time of enrollment on this trial.
d. Greater than or equal to 18 years of age.
e. Willing to sign a durable power of attorney.
f. Able to understand and sign the Informed Consent Document.
g. Clinical performance status of ECOG 0 or 1.
h. Life expectancy of greater than three months.
i. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.
j. Serology:
--1. Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune -competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.).
--2. Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative.
k. Hematology:
--1. Absolute neutrophil count greater than or equal to 1200/mm3 without the support of filgrastim.
--2. WBC (greater than 3000/mm3).
--3. Platelet count greater than 75,000/mm3.
--4. Hemoglobin greater than 8.0 g/dl.
l. Chemistry:
--1. Serum ALT/AST less or equal to 5 times the upper limit of normal.
--2. Serum creatinine less than or equal to 1.6 mg/dl
--3. Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl
m. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo)
EXCLUSION CRITERIA:
a. Patients that require urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression.
b. Patients that have active hemolytic anemia.
c. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
d. Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease
e. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)
f. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities)
g. Concurrent systemic steroid therapy.
h. History of severe immediate hypersensitivity reaction to any of the agents used in this study
i. History of coronary revascularization or ischemic symptoms
j. Any patient known to have an LVEF less than or equal to 45%
k. Documented LVEF of less than or equal to 45% tested in patients with:
--1. History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
--2. Age greater than or equal to 60 years old
l. Documented FEV1 less than or equal to 60% predicted tested in patients with:
--1. A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years)
--2. Symptoms of respiratory dysfunction
m. History of allogeneic stem cell transplantation
n. Patients with CNS metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions).
o. CNS-3 disease or traumatic spinal tap with POSITIVE Steinherz/Bleyer algorithm with cerebral spinal fluid involvement with malignancy will make any patient not eligible for this protocol.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 11/25/2009