LMB-2 to Treat Hairy Cell Leukemia

NCT00321555 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 06015006-C-0150
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hairy Cell Leukemia

Keywords

Biologic Therapy; Monoclonal Antibody; Immunotherapy; Pseudomonas Exotoxin; Targeted Therapy; Hairy Cell Leukemia; HCL

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Duration of Response

  Participants were assessed at 5.0658, 12.0066, 20.1645, 26.9079, 35.0987, and 45.1316 months

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 83 months and 15 days.

Study Arms (1)

LMB-2 to Treat Hairy Cell Leukemia

EXPERIMENTAL

LMB-2 Infusion: 40 micro-g/Kg will be infused in 50 ml of 0.9% Sodium chloride (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.

Drug: Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin

Interventions

Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin DRUG

LMB-2 Infusion: 40 micro-g/Kg will be infused in 50 ml of 0.9% Sodium Chloride (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.

LMB-2 to Treat Hairy Cell Leukemia

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.
• At least 18 years old.
• 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) 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.
• Creatinine less than or equal to 1.4 mg/dL or creatinine clearance greater than or equal to 50 ml/min.
• Serum that neutralizes less than or equal to 75% of the activity of 1 microg/mL of LMB-2 using a bioassay.
• 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.
• No anti-cluster of differentiation 25 (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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 6585795 BACKGROUND

• 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.

  PMID: 9168448 BACKGROUND

• 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.

  PMID: 3555204 BACKGROUND

• Matsushita K, Margulies I, Onda M, Nagata S, Stetler-Stevenson M, Kreitman RJ. Soluble CD22 as a tumor marker for hairy cell leukemia. Blood. 2008 Sep 15;112(6):2272-7. doi: 10.1182/blood-2008-01-131987. Epub 2008 Jul 2.

  PMID: 18596230 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Hairy Cell

Interventions

B3(Fv)-PE38KDEL recombinant immunotoxin; Immunotoxins

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Noxae; Toxic Actions

Results Point of Contact

• Title: Dr. Robert Kreitman
• Organization: National Cancer Institute

robert_kreitman@nih.gov

301-648-7375

Study Officials

• Robert J Kreitman, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 3, 2006
• First Posted: May 4, 2006
• Study Start: May 2, 2006
• Primary Completion: August 24, 2016
• Study Completion: December 31, 2022
• Last Updated: November 14, 2023
• Results First Posted: April 5, 2019

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)