Hairy Cell Leukemia Clinical Trial
Official title:
A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for CD25 Positive Hairy Cell Leukemia
Verified date | October 2023 |
Source | National Institutes of Health Clinical Center (CC) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Background: - About 80% of patients with hairy cell leukemia (HCL) have tumor cells that have a protein on their surface called cluster of differentiation 25 (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.) Objectives: - 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. Eligibility: -Adults with hairy cell leukemia whose tumor cells have CD25 on their surface Design: - 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 computed tomography (CT) scan, echocardiogram (heart ultrasound test) and bone marrow biopsy. With the patient's permission, these tests may be repeated before other cycles also.
Status | Completed |
Enrollment | 15 |
Est. completion date | December 31, 2022 |
Est. primary completion date | August 24, 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 100 Years |
Eligibility | - INCLUSION CRITERIA: 1. Histopathological evidence of cluster of differentiation 25 (CD25)+ Hairy Cell Leukemia (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. 2. At least one of the following indications for treatment: neutropenia (absolute neutrophil count (ANC) less than 1000 cells/ microL), anemia (hemoglobin (Hgb) less than 10g/dL), thrombocytopenia (platelet (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. Eastern Cooperative Oncology Group (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. Alanine aminotransferase (ALT) and aspartate aminotransferase (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-cluster of differentiation 25 (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. 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 less than 45%. - Patients with a diffusing capacity of the lungs for carbon monoxide (DLCO) less than 55% of normal or an forced expiratory volume 1 (FEV1) less than 60% of normal based on either National Institutes of Health (NIH) or United States of America (USA) normal ranges. - Patients who have an active 2nd malignancy requiring systemic treatment. |
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Cancer Institute (NCI) |
United States,
Blasinska-Morawiec M, Robak T, Krykowski E, Hellmann A, Urbanska-Rys H. Hairy cell leukemia-variant treated with 2-chlorodeoxyadenosine--a report of three cases. Leuk Lymphoma. 1997 Apr;25(3-4):381-5. doi: 10.3109/10428199709114177. — View Citation
Carson DA, Wasson DB, Beutler E. Antileukemic and immunosuppressive activity of 2-chloro-2'-deoxyadenosine. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2232-6. doi: 10.1073/pnas.81.7.2232. — View Citation
Cheson BD, Martin A. Clinical trials in hairy cell leukemia. Current status and future directions. Ann Intern Med. 1987 Jun;106(6):871-8. doi: 10.7326/0003-4819-106-6-871. Erratum In: Ann Intern Med 1987 Oct;107(4):604. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Patients Who Obtain Partial Response/Complete Remission | Partial response requires all of the following for a period of at least 4 weeks: =50% decrease in hairy cell count from pretreatment baseline value by flow cytometry. =50% reduction in abnormal hepatosplenomegaly by computed tomography or physical exam. No growth in lymphadenopathy. Neutrophils =1,500/µL or 50% improvement over baseline without growth factors for at least 4 weeks. Platelets =100,000/µL or 50% improvement over baseline. Complete remission requires all of the following: no evidence of leukemic cells by routine hematoxylin and eosin stains of the peripheral blood and bone marrow. No hepatomegaly, splenomegaly, or lymphadenopathy (not >2 cm in short axis) by physical examination and appropriate radiographic techniques. Normal complete blood count as exhibited by Neutrophils =1,500/µL, Platelets =100,000/µL, and Hemoglobin =11.0g/dL without transfusions or growth factors for at least 4 weeks. | 6 months | |
Secondary | Duration of Response | Duration of response is the duration that the patients qualifies for at least a Partial Response (PR). Partial response requires all of the following for a period of at least 4 weeks: =50% decrease in hairy cell count from pretreatment baseline value by flow cytometry. =50% reduction in abnormal hepatosplenomegaly by computed tomography or physical exam. No growth in lymphadenopathy. Neutrophils =1,500/µL or 50% improvement over baseline without growth factors for at least 4 weeks. Platelets =100,000/µL or 50% improvement over baseline. Hemoglobin =11.0 g/dL or 50% improvement over baseline without transfusions or growth factors for at least 4 weeks. | Participants were assessed at 5.0658, 12.0066, 20.1645, 26.9079, 35.0987, and 45.1316 months | |
Secondary | Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) | Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. | Date treatment consent signed to date off study, approximately 83 months and 15 days. |
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