LMB-2 Immunotoxin in Treating Patients with Hairy Cell Leukemia
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.
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Additional locations may be listed on ClinicalTrials.gov for NCT00321555.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
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).
SECONDARY OBJECTIVES:
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.
OUTLINE:
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.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationNCI - Center for Cancer Research
Principal InvestigatorRobert J. Kreitman
- Primary ID7834
- Secondary IDsNCI-2009-00231, 06-C-0150, NCT00337311, CDR0000482415, P6760
- ClinicalTrials.gov IDNCT00321555