NIH Clinical Research Studies

Protocol Number: 04-C-0121

Active Accrual, Protocols Recruiting New Patients

Title:
A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for Treatment of CD25 Positive Chronic Lymphocytic Leukemia
Number:
04-C-0121
Summary:
This study will evaluate the effectiveness of an experimental drug called LMB-2 for treating chronic lymphocytic leukemia (CLL) in patients who have a protein called CD25 on their cancer cells. LMB-2 is a recombinant immunotoxin. It is made up of two parts: a genetically engineered monoclonal antibody that binds to cancer cells with CD25 on their surface, and a toxin produced by bacteria that kills the cancer cells to which it binds. LMB-2 has killed CD 25-containing cells in laboratory experiments and has caused tumors in mice to shrink. Preliminary studies in humans have shown some effectiveness in shrinking tumors in patients with various types of lymph and blood cancers.

Patients 18 years of age and older with CLL who have CD25 receptor proteins on their cancer cells and whose disease has progressed within 2 years of treatment with fludarabine may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG), echocardiogram, chest x-ray, CT scans of the chest, abdomen and pelvis, and a bone marrow biopsy.

Participants receive up to six cycles of LMB-2 therapy. Each 28-day cycle consists of 30-minute infusions of LMB-2 on cycle days 1, 3, and 5. The drug is infused through an intravenous (IV) catheter (plastic tube placed in a vein) or a central venous line-an IV tube placed in a large vein in the neck or chest that leads to the heart. Patients are admitted to the NIH Clinical Center for the first treatment cycle. If the infusion is well tolerated, subsequent cycles may be given on an outpatient basis. In addition to drug therapy, patients undergo the following procedures:

-Blood draws: Blood is drawn before, during, and after each LMB-2 infusion to measure blood levels of the drug, evaluate its effects on the cancer cells, and monitor side effects. Blood tests are also done before and during each cycle to determine how the immune system is interacting with the drug.

-Disease evaluations: Patients undergo a physical examination, blood tests, chest x-ray, and EKG before each treatment cycle and at follow-up visits. With the patient's permission, CT scans, echocardiogram, and bone marrow biopsies may be repeated before some treatment cycles if these tests prove useful in evaluating the disease response to LMB-2.

Patients may receive up to six cycles of LMB-2 as long as their cancer does not worsen and they do not develop serious side effects. At the end of the treatment cycles, patients will have blood tests done weekly by their local physician, and the results will be sent to the NCI study investigators.

Sponsoring Institute:
National Cancer Institute (NCI)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): None

Eligibility Criteria:
INCLUSION CRITERIA:

Patients must have histopathological evidence of CD25+ CLL confirmed by the NIH pathology department. This requires that at least 50% of the peripheral malignant lymphocytes be 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.

In the three stage modified Rai system, patients must be intermediate or high risk. This means they must have lymphocytosis (leukemic cells greater than 5000/ul) and at least one of the following: lymphadenopathy, splenomegaly, hepatomegaly, anemia (Hgb less than 11g/dL), or thrombocytopenia (Plt less than 100,000/ul).

Patients must have had progressive disease within 2 years of receiving fludarabine.

Patients must not have received 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.

ECOG performance status of 0 - 2.

At least 18 years old.

Patients must be able to understand and give informed consent.

Female patients of childbearing potential must have a negative pregnancy test and all patients must use effective contraception (a barrier form of contraception).

The transaminases ALT and AST must each be less than or equal to 2.5-times the upper limits of normal. Albumin must be greater than or equal to 3.0 gm/dL. Total bilirubin must be less than or equal to 2.2 mg/dL except in patients with Gilbert's syndrome (as defined by greater than 80% unconjugated bilirubin) it must be less than 5 mg/dl.

The creatinine must be less than or equal to 1.4 mg/dL or the creatinine clearance must be greater than or equal to 50 ml/min as measured from a 24-hour urine collection.

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.

EXCLUSION CRITERIA:

Patients whose serum neutralizes LMB-2 in tissue culture, due either to anti-toxin or anti-mouse-lgG antibodies. No patient whose serum neutralizes greater than 75% of the activity of 1 micro g/mL of LMB-2 will be treated.

Patients who received LMB-2 on another trial.

Monoclonal antibody therapy within 12 weeks of enrollment.

Patients who are pregnant or breast-feeding.

Patients who are HIV positive or hepatitis B surface antigen positive.

Patients who have hepatitis C or chronic liver disease.

Patients on chronic anticoagulation.

Patients with a left ventricular ejection fraction of less than the institutional lower limit of normal.

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

Patients who have active cancer requiring treatment.

Special Instructions: Currently Not Provided
Keywords:
LMB-2
Chronic Lymphocytic Leukemia
CLL
Immunotoxin
Oncology
Recruitment Keywords:
Chronic Lymphocytic Leukemia
CLL
Conditions:
Leukemia
Lymphocytic
Chronic
Investigational Drug(s):
LMB-2
Investigational Device(s):
None

Contacts:
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:
Cheson BD, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996 Jun 15;87(12):4990-7. No abstract available. PMID: 8652811

Harris NL, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol. 1999 Dec;17(12):3835-49. PMID: 10577857

Rai KR, Sawitsky A. A review of the prognostic role of cytogenetic, phenotypic, morphologic, and immune function characteristics in chronic lymphocytic leukemia. Blood Cells. 1987;12(2):327-38. Review. PMID: 3304471

Active Accrual, Protocols Recruiting New Patients

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