This study will examine the safety and effectiveness of the experimental drug BL22 for treating hairy cell leukemia. BL22 can kill leukemia cells that have a protein on their surface called CD22. The drug is made up of two parts - a protein that binds to the CD22 protein on a cancer cell and a toxin (type of poison) that kills the cancer cell to which it binds. In a preliminary study of BL22 in patients with leukemias and lymphomas, several patients with hairy cell leukemia have achieved disease remission ranging from 6 to 43 months.

Patients 18 years of age and older with hairy cell leukemia whose cancer cells have the CD22 protein may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, electrocardiogram (EKG), chest x-ray, and bone marrow biopsy.

Participants will undergo the following tests and procedures:

- BL22 treatment: BL22 is given by intravenous (through a vein) infusion over 30 minutes on days 1, 3, and 5 of each 4-week treatment cycle. The drug is infused through a central venous catheter (plastic tube placed in a large vein). The first infusion is given on an inpatient basis, with subsequent cycles given as outpatients. Acetaminophen, ranitidine, and hydroxyzine are given around the time of the BL22 infusion to reduce the risk of an allergic reaction to the drug. Other treatments, such as transfusions and antibiotics, are given if required. Patients are evaluated 8 weeks after the first cycle. Those whose blood counts improve to a certain level are observed without further treatment. Others may receive up to 9 nine additional cycles of BL22 every 4 weeks unless the disease worsens, serious side effects develop, or the patient decides to withdraw from the study.

- Blood tests: A small amount of blood is drawn before, during, and after each treatment cycle to measure the amount of BL22 in the blood, the effects of the drug on cancer cells in the blood, and to monitor for drug side effects. Blood tests are also done before and during each cycle to assess the immune system response to BL22.

- Disease progress is evaluated before each cycle and at follow-up visits. These evaluations include a physical examination, blood tests, chest x-ray, and electrocardiogram (EKG). Bone marrow biopsy, computed tomography (CT) scan, and echocardiogram (heart ultrasound test) are done before starting the first treatment cycle and after every two cycles, or more often if they contribute to an understanding of how the leukemia is reacting to BL22.

Condition	Treatment or Intervention	Phase
Leukemia, Hairy Cell	Drug: BL22	Phase II

Further Study Details: 

Expected Total Enrollment:  45

The purpose of this study is to determine the activity of BL22 in patients with cladribine-resistant Hairy Cell Leukemia (HCL). All leukemic hairy cells intensely express CD22, a membrane protein associated with B cell signaling. BL22 is an anti-CD22 recombinant immunotoxin containing the variable domains of MAb RFB4 (anti-CD22) and truncated Pseudomonas exotoxin. A phase I trial of BL22 at NCI demonstrated that patients with cladribine-resistant HCL had a high response rate to BL22. Of the first 25 HCL patients, 18 had complete remissions and 2 had partial remissions. Those who did not respond had received lower doses of BL22, developed neutralizing antibodies against BL22, or had bulky lymphadenopathy. The dose limiting toxicity was hemolytic uremic syndrome in 5 patients. Four of these patients had HCL and recovered completely. All 4 had clinical benefit and 3 went into complete remissions. An additional 6 patients were enrolled at a lower dose (30 micro g/Kg IV given every other day for 3 doses (QOD x 3) on cycle 1 and 20 micro g/Kg on cycles 2-5) and treated every 6 weeks (instead of every 3-4 weeks). Of these 6 patients, none had dose limiting toxicity and 1 had a CR. The primary endpoint of this phase II trial is to determine the response rate of cladribine-resistant HCL patients to BL22. We will also evaluate response duration, BL22 immunogenicity, blood levels of BL22, and toxicity.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
1. Histopathological evidence of CD22+ HCL confirmed by the NIH pathology department. This will require a monoclonal population of peripheral malignant lymphocytes that are CD22 positive by fluorescence activated cell sorting (FACS) with anti-CD22 antibody. Positive expression in a FACS assay is defined as more than 2 times the mean fluorescence intensity (MFI) of the control antibody by FACS.
2. At least one of the following indications for treatment: neutropenia (ANC less than 1000 cells/ul), anemia (Hgb less than 10g/dL), thromobocytopenia (Plt less than 100,000/ul), an absolute lymphocyte count of greater than 20,000 cells/ul, or symptomatic splenomegaly.
3. No response or less than a 2 year duration of CR or PR after the last course of cladribine, or less than a 4 year duration of CR or PR to a 2nd or later course of cladribine.
4. ECOG performance status of 0-2, unless due to potentially reversible active uncontrolled infection.
5. At least 18 years old.
6. Understand and give informed consent.
7. A negative pregnancy test in female patients of childbearing potential. Women must not be breast-feeding.
8. ALT and AST less than or equal to 2.5 times the upper limits of normal. Albumin greater than or equal to 3.0 gm/dL. Total bilirubin less than or equal to 2.2mg/dL.
9. Creatinine less than or equal to 1.4 mg/dL or creatinine clearance greater than or equal to 50 ml/min.
10. Serum that neutralizes less than or equal to 75% of the activity of 1 micro g/mL of BL22 using a bioassay.
11. No systemic cytotoxic chemotherapy within 4 weeks of enrollment or systemic steroids (except stable doses of Prednisone less than or equal to 20 mg/day) within 4 weeks of enrollment.
12. No monoclonal antibody therapy within 12 weeks of enrollment.
13. No prior treatment with BL22.
14. Patients may not be receiving any other investigational agents.
15. Hepatitis B surface antigen negative.
16. Patients should not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
17. Patients with uncontrolled ongoing or active infection may be reviewed with and approved individually by the sponsor if the infection is deemed reversible by response to BL22, and if the patient had no PR/CR to the last courses of purine analog and rituximab.

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

Study ID Numbers:  040014; 04-C-0014
Record last reviewed:  February 3, 2005
Last Updated:  March 15, 2005
Record first received:  October 17, 2003
ClinicalTrials.gov Identifier:  NCT00071318
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08