Protocol Number: 06-C-0150

Title:

A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for CD25 Positive Hairy Cell Leukemia

Number:

06-C-0150

Summary:

Background:

-About 80% of patients with hairy cell leukemia (HCL) have tumor cells that have a protein on their surface called CD25.

-The experimental drug LMB-2 is a recombinant immunotoxin that has been shown to kill leukemia and lymphoma cells with the CD25 protein. (A recombinant immunotoxin is a genetically engineered drug that has two parts - a protein that binds or targets a cancer cell, and a toxin that kills the cancer cell to which it binds.)

Objectives:

-To evaluate the safety and effectiveness of LMB-2 in patients with HCL whose cancer cells contain the CD25 protein.

-To evaluate the effects of LMB-2 on the immune system, determine how the drug is metabolized by the body and examine its side effects.

Eligibility:

-Adults with hairy cell leukemia whose tumor cells have CD25 on their surface

Design:

-Up to 27 patients may be included in the study.

-Patients receive an infusion of LMB-2 through a vein every other day for three doses (days 1, 3, 5), constituting one treatment cycle.

-Patients may receive up to six treatment cycles every 4 weeks unless their cancer worsens or they develop unacceptable side effects.

-Blood is drawn weekly for various tests.

-Before each cycle and in follow-up visits, disease status is evaluated with a physical examination, blood tests, chest x-ray and electrocardiogram.

-Before the first cycle, patients may have a CT scan, echocardiogram (heart ultrasound test) and bone marrow biopsy. With the patient's permission, these tests may be repeated before other cycles also.

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 CD25+ HCL confirmed by the NIH pathology department. This will require a monoclonal population of peripheral malignant lymphocytes that are CD25 positive by fluorescence activated cell sorting (FACS) with anti-CD25 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. HCLv (HCL variant) is usually CD25 negative, and eligibility would require CD25+ HCLv.

2. At least one of the following indications for treatment: neutropenia (ANC less than 1000 cells/ul), anemia (Hgb less than 10g/dL), thrombocytopenia (Plt less than 100,000/ul), an absolute lymphocyte count of greater than 20,000 cells/ul or symptomatic splenomegaly.

3. Previous treatment with or inability to receive BL22 recombinant immunotoxin. Patients must have had at least 2 prior systemic therapies. There must have been at least 2 prior courses of purine analog, or 1 if the response to this course lasted less than 2 years, or if the patient had unacceptable toxicity to purine analog.

4. ECOG performance status of 0 - 2.

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 5-times the upper limits of normal. Albumin greater than or equal to 3.0 gm/dL. Total bilirubin less than or equal to 2.2 mg/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 microg/mL of LMB-2 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, or up to 4 doses of steroid given for non-therapy reasons) within 4 weeks of enrollment.

12. No monoclonal antibody therapy within 4 weeks of enrollment, and not anti-Tac monoclonal antibody within 12 weeks of enrollment.

13. No prior treatment with LMB-2.

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.

EXCLUSION CRITERIA:

-Patients who have HIV or hepatitis C. Patients would not be excluded for hepatitis B surface antigen positivity if on Lamivudine.

- Patients receiving coumadin.

- Patients with a left ventricular ejection fraction of less than 45%.

- Patients with a DLCO less than 55% of normal or an FEV1 less than 60% of normal.

-Patients who have an active 2nd malignancy requiring systemic treatment.

Special Instructions:

Currently Not Provided

Keywords:

Biologic Therapy

Monoclonal Antibody

Immunotherapy

Pseudomonas Exotoxin

Targeted Therapy

Recruitment Keyword(s):

Hairy Cell Leukemia

HCL

Condition(s):

Positive Hairy Cell Leukemia

CD25-Expressing Hairy Cell Leukemia

Investigational Drug(s):

LMB-2

Investigational Device(s):

None

Intervention(s):

Drug: LMB-2

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):

Carson DA, Wasson DB, Beutler E. Antileukemic and immunosuppressive activity of 2-chloro-2'-deoxyadenosine. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2232-6.

Blasinska-Morawiec M, Robak T, Krykowski E, Hellmann A, Urbanska-Rys H. Hairy cell leukemia-variant treated with 2-chlorodeoxyadenosine--a report of three cases. Leuk Lymphoma. 1997 Apr;25(3-4):381-385.

Cheson BD, Martin A. Clinical trials in hairy cell leukemia. Current status and future directions. Ann Intern Med. 1987 Oct;107(4):604: Ann Intern Med, 106: 871-8878, 1987.

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