LMB-2 Immunotoxin in Treating Patients with Hairy Cell Leukemia
Basic Trial Information
|Phase II||Biomarker/Laboratory analysis, Treatment||Active||18 and over||06-C-0150|
NCI-2009-00231, CDR0000482415, NCT00337311, P6760, 7834, NCI-06-C-0150, NCI-P6760, NCI-7834, NCT00321555
This phase II trial studies how well anti-Tac(Fv)-PE38 (LMB-2) immunotoxin works in treating patients with hairy cell leukemia. The LMB-2 immunotoxin can find cancer cells and kill them without harming normal cells. This may be an effective treatment for hairy cell leukemia.
Further Study Information
I. To determine the response rate of LMB-2 (LMB-2 immunotoxin) in patients with cluster of differentiation (CD)25-positive hairy cell leukemia (HCL).
I. To describe the response duration.
II. To describe how blood levels of LMB-2 (area under curve [AUC], maximum concentration [Cmax]) are related to toxicity.
III. To describe how the development of neutralizing antibodies affects blood levels of LMB-2 and toxicity.
IV. To describe how soluble Tac-peptide (soluble interleukin-2 receptor alpha [sIL2Ra]) levels correlate with response to treatment with LMB-2.
Patients receive LMB-2 immunotoxin intravenously (IV) over 30 minutes on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) may receive 2 additional courses beyond CR. Patients achieving CR with minimal residual disease (MRD) may receive up to 4 additional courses beyond CR with MRD. Patients who relapse after > 2 months of a CR or partial response may be eligible for retreatment.
After completion of study treatment, patients are followed up every 3 - 12 months.
Histopathological evidence of CD25+ HCL confirmed by the National Institutes of Health (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
At least one of the following indications for treatment:
Neutropenia (absolute neutrophil count [ANC] < 1000 cells/ul)
Anemia (hemoglobin [Hgb] < 10 g/dL)
Thrombocytopenia (platelets [Plt] < 100,000/ul)
Absolute lymphocyte count of > 20,000 cells/ul or symptomatic splenomegaly
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 B-RAF proto-oncogene, serine/threonine kinase gene (BRAF) inhibitor following a single prior course of PNA
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Understand and give informed consent
A negative pregnancy test in female patients of childbearing potential; women must not be breast-feeding
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 times upper limit of normal
Albumin >= 3.0 gm/dL
Total bilirubin =< 2.2 mg/dL
Creatinine =< 1.4 mg/dL or creatinine clearance >= 50 mL/min
Serum that neutralizes =< 75% of the activity of 1 ug/mL of LMB-2 using a bioassay
No systemic cytotoxic chemotherapy within 4 weeks of enrollment or systemic steroids (except stable doses of prednisone =< 20 mg/day, or up to 4 doses of steroid given for non-therapy reasons) within 4 weeks of enrollment
No anti-CD25 monoclonal antibody therapy within 12 weeks of enrollment
No prior treatment with LMB-2
Patients may not be receiving any other investigational agents
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 human immunodeficiency virus (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 < 45%
Patients with a diffusing capacity of the lung for carbon monoxide (DLCO) < 55% of normal or a forced expiratory volume in one second (FEV1) < 60% of normal, based on either NIH or United States (USA) normal ranges
Patients who have an active 2nd malignancy requiring systemic treatment
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
National Cancer Institute
- National Cancer Institute
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT00321555
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.