The purpose of the study is to evaluate the toxicity following administration of the recombinant immunotoxin BL22 in patients with CD22-positive malignancies (e.g., B-cell non-Hodgkin's lymphomas, chronic lymphocytic leukemia, prolymphocytic leukemia and hairy cell leukemia). The scientific basis for the proposed therapeutic study is that patients with these malignancies have cells which express high levels of the CD22 antigen on their cell surface. We propose to administer the immunotoxin BL22 to adult patients with CD22+ malignancies who fulfill the patient eligibility criteria. Patients will be followed closely for evidence of clinical or laboratory toxicity. Clinical response will be evaluated using routine hematologic and clinical evaluation and, when deemed appropriate by the Principal Investigator, by monitoring the phenotype of circulating B-cells or of biopsied tissues using antibodies to CD22. Serum concentrations of the administered immunotoxin and levels of anti-immunotoxin antibodies produced by the patients will also be monitored.

Condition	Treatment or Intervention	Phase
Chronic Lymphocytic Leukemia Hairy Cell Leukemia Non Hodgkin's Lymphoma Prolymphocytic Leukemia	Drug: BL22	Phase I

Further Study Details: 

Expected Total Enrollment:  46

The purpose of the study is to evaluate the toxicity following administration of the recombinant immunotoxin BL22 in patients with CD22-positive malignancies (e.g., B-cell non-Hodgkin's lymphomas, chronic lymphocytic leukemia, prolymphocytic leukemia and hairy cell leukemia). The scientific basis for the proposed therapeutic study is that patients with these malignancies have cells which express high levels of the CD22 antigen on their cell surface. We propose to administer the immunotoxin BL22 to adult patients with CD22+ malignancies who fulfill the patient eligibility criteria. Patients will be followed closely for evidence of clinical or laboratory toxicity. Clinical response will be evaluated using routine hematologic and clinical evaluation and, when deemed appropriate by the Principal Investigator, by monitoring the phenotype of circulating B-cells or of biopsied tissues using antibodies to CD22. Serum concentrations of the administered immunotoxin and levels of anti-immunotoxin antibodies produced by the patients will also be monitored. In a later phase of this trial, only patients with hairy cell leukemia will be enrolled, and patients with other CD22+ malignancies may be eligible for a different phase I trial of BL22.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
All newly enrolled patients must have a confirmed diagnosis of hairy cell leukemia.
Patients must have evidence of CD22 positivity by the following criteria:
Greater than 15% of malignant cells from a site must react with anti-CD22 by immunohistochemistry or
Greater than 30% of malignant cells from a site CD22+ by FACS or
Greater than 400 CD22 sites/cell (average) on malignant cells as assessed by radiolabeled anti-CD22 binding.
Stage of Disease:
HCL: Patients with hairy cell leukemia are eligible if they have relapsed after purine analog therapy and if they had less than 2 years of complete remission to their last purine analog therapy. They must have at least one indication for therapy including 1) progressive or massive splenomegaly, 2) cytopenia (ANC less than 1000/mm(3), PLT less than 100,000/mm(3) , or Hgb less than 12mg/dl), 3) greater than 20,000 circulating hairy cells/mm(3), 4) symptomatic adenopathy, or 5) constitutional symptoms including tumor-related fever or bone pain.
Patients will not be ineligible because of prior bone marrow transplantation.
Patients must have a Karnofsky performance status of at least 60.
Patients must be able to understand and sign informed consent.
Omission of cytotoxic chemotherapy, whole body electron beam radiation therapy, interferon, retinoids or other systemic therapy of the malignancy for 3 weeks prior to entry into the trial. Patients must be greater than 3 months from any monoclonal antibody therapy such as rituximab. Patients who have received or are receiving radiation therapy less than 3 weeks prior to study entry will not be excluded providing the volume of bone marrow treated is less than 10% and also the patient has measurable disease outside the radiation port.
Patients must have a life expectancy of greater than 6 months.
Patients must be at least 18 years old.
The transaminases ALT and AST must each be less than 2.5 times the upper limits of normal and the bilirubin must be less than 1.5-fold the upper limits of normal.
Serum creatinine must not be greater than 2.0 mg/dL.
Patients must have greater than or equal to 60% of predicted forced expiratory volume (FEV1) and greater than or equal to 55% of predicted diffusing capacity for carbon monoxide (DLCO), as assessed by pulmonary function studies.
Patients with childbearing potential are required to practice contraception during the study.
EXCLUSION CRITERIA:
Female patients of child-bearing potential will be tested for pregnancy by urine obtained during the week before beginning BL22; pregnant patients will be excluded from the study due to unknown effects of BL22 on the fetus. Breast feeding women will be excluded from the study because it is not known whether BL22 would cause adverse effects on the baby and/or mother in this situation.
Patients who are HIV-antibody positive, due to the difficulty in separating drug-related toxicity from HIV-related problems in such patients.
Patients with central nervous system disease who require treatment.
Patients whose serum neutralizes BL22 in tissue culture, due either to anti-toxin or anti-mouse-IgG antibodies. No patient whose serum neutralizes greater than 75% of the activity of 1 microgram/mL of BL22 will be treated. Guidelines more strict than this may be used at the discretion of the principal investigator. This criteria shall apply for patients to be treated with one exception. If a patient achieves a peak plasma level during the prior cycle of greater than 1 microgram/ml and develops antibodies which neutralize greater than 75% of the activity of 1 microgram/ml but less than 50% of the activity of a concentration of BL22 which is less than the previous peak plasma level, that patient would not be disqualified from retreatment due to immunogenicity.
Patient may not receive BL22 while on therapeutic coumadin therapy.

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States

Study ID Numbers:  990014; 99-C-0014
Record last reviewed:  November 1, 2004
Last Updated:  November 23, 2004
Record first received:  November 3, 1999
ClinicalTrials.gov Identifier:  NCT00001792
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08