Protocol Number: 04-C-0014

Title:

Phase II Trial of BL22 Immunotoxin in Hairy Cell Leukemia

Number:

04-C-0014

Summary:

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.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility 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) for treatment within 4 weeks of enrollment. Patients receiving a limited number of doses (less than 5) of steroid for non-treatment reasons (e.g. allergy prophylaxsis connected with medical testing), may not receive any steroid within one week of enrollment and may not have had any evidence of disease response to steroid.

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. Patients should not have uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

16. 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.

Special Instructions:

Currently Not Provided

Keywords:

BL22

HCL

Immunotoxin

Oncology

Hairy Cell Leukemia

Recruitment Keyword(s):

None

Condition(s):

Leukemia, Hairy Cell

Investigational Drug(s):

BL22 {RFB4(dsFv)-PE38}

Investigational Device(s):

None

Intervention(s):

Drug: BL22 {RFB4(dsFv)-PE38}

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Frassoldati A, Lamparelli T, Federico M, Annino L, Capnist G, Pagnucco G, Dini E, Resegotti L, Damasio EE, Silingardi V. Hairy cell leukemia: a clinical review based on 725 cases of the Italian Cooperative Group (ICGHCL). Italian Cooperative Group for Hairy Cell Leukemia. Leuk Lymphoma. 1994 Apr;13(3-4):307-16. Review.

BOURONCLE BA, WISEMAN BK, DOAN CA. Leukemic reticuloendotheliosis. Blood. 1958 Jul;13(7):609-30. No abstract available.

Vardiman JW, Golomb HM. Autopsy findings in hairy cell leukemia. Semin Oncol. 1984 Dec;11(4):370-80.

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