LMB-2 to Treat Hairy Cell Leukemia
- 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.)
- 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.
-Adults with hairy cell leukemia whose tumor cells have CD25 on their surface
- 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.
Positive Hairy Cell Leukemia
CD25-Expressing Hairy Cell Leukemia
|Study Design:||Allocation: Non-Randomized
Primary Purpose: Treatment
|Official Title:||A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for CD25 Positive Hairy Cell Leukemia|
- Response rate [ Designated as safety issue: No ]
- Response duration [ Designated as safety issue: No ]
- Immunogenicity of LMB-2 immunotoxin [ Designated as safety issue: No ]
- Pharmacokinetics [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
- Soluble Tac levels in the serum [ Designated as safety issue: No ]
|Study Start Date:||April 2006|
|Estimated Study Completion Date:||October 2015|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Background: About 80% of patients with hairy cell leukemia (HCL) have malignant cells that express CD25 (Tac or IL2R alpha ). Normal resting B- and T-cells do not express CD25. LMB-2 is an anti-CD25 recombinant immunotoxin containing variable domains of MAb anti-Tac and truncated Pseudomonas exotoxin. A phase I trial at NCI found that the MTD of LMB-2 was 40 microg/Kg IV given every other day for 3 doses (QOD x3). The most common adverse events were transient fever, hypoalbuminemia and transaminase elevations. In that trial, 4 of 4 patients with chemoresistant HCL had major responses, including one complete (CR) and 3 partial remissions. The patient with CR entered the trial transfusion dependent and now still has normal hemoglobin and platelet counts over 7 years later. Because HCL is more frequently CD22+ than CD25+ (100 vs 80%), HCL patients were subsequently treated with the anti-CD22 recombinant immunotoxin BL22 and no further HCL patients were treated with LMB-2. BL22 has induced 25 CRs out of 51 evaluable HCL patients. LMB-2 may be useful in patients incompletely responding to BL22, because it may distribute more evenly through extravascular sites of disease. Moreover, BL22 but not LMB-2 has caused hemolytic uremic syndrome (HUS) in 7 patients, 6 with HCL, and several of these patients could benefit by LMB-2. Thus, LMB-2 may be a useful and potentially lifesaving agent in patients who are unable to receive or who have not responded adequately to BL22.
Objectives: The purpose of this study is to determine the activity of anti-Tac(Fv)-PE38 (LMB-2) in patients with CD25-expressing hairy cell leukemia (HCL). The primary endpoint of this trial is response rate. We will also evaluate response duration, LMB-2 immunogenicity, pharmacokinetics, toxicity, and monitor soluble Tac levels in the serum.
Eligibility: Patients must have CD25+ HCL cells by flow cytometry, cytopenia or high circulating HCL count, prior treatment with or inability to receive BL22, prior treatment with cladribine, ECOG PS 0-2, at least 18 years old, ALT and AST grade 0-2, albumin grade 0-1, bilirubin less than or equal to 2.2, creatinine less than or equal to 1.4 or creatinine clearance greater than or equal to 50, lack of high levels of neutralizing antibodies, lack of systemic treatment for 4 weeks, no prior treatment with LMB-2, lack of other uncontrolled illness including 2nd malignancy, no HIV or hepatitis C positivity, no coumadin therapy, LVEF greater than or equal to 45%, DLCO greater than or equal to 55%, and FEV1 greater than or equal to 60%.
Design: Patients will receive LMB-2 at 40 microg/Kg QOD x3 at intervals of at least 25 days for up to 6 cycles. Retreatment is permitted in the absence of neutralizing antibodies or progressive disease. Patients in CR may receive 2 consolidation cycles, or 4 consolidation cycles if CR is with minimal residual disease.
Dose level: LMB-2 40 microg/Kg QOD x3
Expected Accrual: 5-10 patients/year, total of 25 patients
Please refer to this study by its ClinicalTrials.gov identifier: NCT00321555
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Robert J Kreitman, M.D.||National Cancer Institute (NCI)|