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LMB-2 to Treat Hairy Cell Leukemia

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ClinicalTrials.gov Identifier: NCT00321555
Recruitment Status : Active, not recruiting
First Posted : May 4, 2006
Last Update Posted : October 19, 2017
Information provided by (Responsible Party):

May 3, 2006
May 4, 2006
October 19, 2017
May 2, 2006
March 31, 2018   (Final data collection date for primary outcome measure)
Response rate [ Time Frame: 6 months ]
Not Provided
Complete list of historical versions of study NCT00321555 on ClinicalTrials.gov Archive Site
Duration of Response [ Time Frame: 6 months ]
Not Provided
Not Provided
Not Provided
LMB-2 to Treat Hairy Cell Leukemia
A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for CD25 Positive 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.

Background: About 80% of patients with hairy cell leukemia (HCL) have malignant cells that express CD25 (Tac or IL2Ra). 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 anti-CD25 Mab therapy for 12 weeks and other 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

Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Hairy Cell Leukemia
Drug: Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin
LMB-2 Infusion: 40 micro-g/Kg will be infused in 50 ml of 0.9% NaCl and 0.2% albumin via over 30 minutes every other day for 3 doses. Patients may receive up to six treatment cycles every 4 weeks.
Experimental: A
LMB-2 Infusion: 40 micro-g/Kg will be infused in 50 ml of 0.9% NaCl and 0.2% albumin via over 30 minutes every other day for 3 doses. Patients may receive up to six treatment cycles every 4 weeks.
Intervention: Drug: Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Active, not recruiting
March 31, 2019
March 31, 2018   (Final data collection date for primary outcome measure)

    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/ microL), anemia (Hgb less than 10g/dL), thrombocytopenia (Plt less than 100,000/ microL), an absolute lymphocyte count of greater than 20,000 cells/microL or symptomatic splenomegaly.
    3. Previous treatment with or inability to receive BL22 or HA22 recombinant immunotoxin. Patients must have had at least 2 prior systemic therapies, including 2 courses of a purine nucleoside analog (PNA), or 1 course of either rituximab or BRAF inhibitor following a single prior course of PNA.
    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 anti-CD25 monoclonal antibody therapy 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.


  • 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 based on either NIH or USA normal ranges.
  • Patients who have an active 2nd malignancy requiring systemic treatment.
Sexes Eligible for Study: All
18 Years to 100 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
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National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
National Cancer Institute (NCI)
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Principal Investigator: Robert J Kreitman, M.D. National Cancer Institute (NCI)
National Institutes of Health Clinical Center (CC)
June 7, 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP