|
|
Home
Search
Study Topics
Glossary
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
||||||||||||||||||||||||||||||||||||
| Sponsor: | National Cancer Institute (NCI) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00077922 |
Purpose
This study will evaluate the effectiveness of an experimental drug called LMB-2 for treating chronic lymphocytic leukemia (CLL) in patients who have a protein called CD25 on their cancer cells. LMB-2 is a recombinant immunotoxin. It is made up of two parts: a genetically engineered monoclonal antibody that binds to cancer cells with CD25 on their surface, and a toxin produced by bacteria that kills the cancer cells to which it binds. LMB-2 has killed CD 25-containing cells in laboratory experiments and has caused tumors in mice to shrink. Preliminary studies in humans have shown some effectiveness in shrinking tumors in patients with various types of lymph and blood cancers.
Patients 18 years of age and older with CLL who have CD25 receptor proteins on their cancer cells and whose disease has progressed within 2 years of treatment with fludarabine may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG), echocardiogram, chest x-ray, CT scans of the chest, abdomen and pelvis, and a bone marrow biopsy.
Participants receive up to six cycles of LMB-2 therapy. Each 28-day cycle consists of 30-minute infusions of LMB-2 on cycle days 1, 3, and 5. The drug is infused through an intravenous (IV) catheter (plastic tube placed in a vein) or a central venous line-an IV tube placed in a large vein in the neck or chest that leads to the heart. Patients are admitted to the NIH Clinical Center for the first treatment cycle. If the infusion is well tolerated, subsequent cycles may be given on an outpatient basis. In addition to drug therapy, patients undergo the following procedures:
Patients may receive up to six cycles of LMB-2 as long as their cancer does not worsen and they do not develop serious side effects. At the end of the treatment cycles, patients will have blood tests done weekly by their local physician, and the results will be sent to the NCI study investigators.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia Lymphocytic Chronic |
Drug: LMB-2 |
Phase II |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for Treatment of CD25 Positive Chronic Lymphocytic Leukemia |
| Enrollment: | 15 |
| Study Start Date: | February 2004 |
| Study Completion Date: | December 2011 |
| Primary Completion Date: | December 2011 (Final data collection date for primary outcome measure) |
Background:
It is estimated that 30-50% of patients with CLL have tumors that express CD25 (Tac or IL2R). Normal resting T-cells are not sensitive to LMB-2 due to insufficient CD25 expression. 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) with prophylactic IV fluid. The most common adverse events were transient fever, hypoalbuminemia and transaminase elevations. In that trial, one of eight patients with chronic lymphocytic leukemia had a partial remission. The other seven CLL patients had stable disease. In addition, four of four patients with hairy cell leukemia had responses (1 CR, 3 PRs) and 3 other patients had PRs (1 CTCL, 1 HD, 1 ATL). Because LMB-2 is cytotoxic to cells expressing CD25, CD25+ CLL patients are good candidates for further testing with LMB-2.
Objectives:
The purpose of this study is to determine the activity of anti-Tac(Fv)-PE38 (LMB- 2) in patients with Tac-expressing Chronic Lymphocytic Leukemia (CLL). 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:
CD25 positive CLL or prolymphocytic leukemia (PLL) confirmed by flow cytometry of blood, with either lymphadenopathy, splenomegaly, hepatomegaly, hemoglobin ;ess than 11 g/dl, or platelets less than 100,000/ul. Patients must have progression following purine analog or alkylating agent. Labs required: ALT and AST less than or equal to 2.5- time upper limit, albumin greater than or equal to 3, bilirubin less than equal to 2.2 (unless unconjugated greater than or equal to 80%) and creatinine less than or equal to 1.4 (unless creatinine clearance greater than or equal to 50 ml/min).
Design:
Patients receive LMB-2 40 ug/Kg QOD x3 every 4 weeks in absence of neutralizing antibodies or progressive disease. 1st stage is 16 patients, to expand to 25 if greater than 1 of 16 patients respond.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Patients must have histopathological evidence of CD25+ CLL or prolymphoctic leukemia (PLL) confirmed by the NIH pathology department. This requires that at least 50% of the peripheral malignant lymphocytes be 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, or greater than 400 CD25 sites/cell by FACS or radiolabeled binding assay.
In the three stage modified Rai system, patients must be intermediate or high risk. This means they must have circulating CLL cells and at least one of the following: lymphadenopathy, splenomegaly, hepatomegaly, anemia (Hgb less than 11g/dL), or thrombocytopenia (Plt less than 100,000/ul).
Patients must have had progressive disease after prior standard therapy containing either a purine analog or an alkylating agent.
Patients must not have received systemic cytotoxic chemotherapy within 4 weeks of enrollment or systemic steroids (except stable doses of Prednisone less than or equal to 20 mg/day) within 4 weeks of enrollment.
ECOG performance status of 0 - 2.
At least 18 years old.
Patients must be able to understand and give informed consent.
Female patients of childbearing potential must have a negative pregnancy test and all patients must use effective contraception (a barrier form of contraception).
The transaminases ALT and AST must each be less than or equal to 2.5-times the upper limits of normal. Albumin must be greater than or equal to 3.0 gm/dL. Total bilirubin must be less than or equal to 2.2 mg/dL except in patients with Gilbert's syndrome (as defined by greater than 80% unconjugated bilirubin) it must be less than 5 mg/dl.
The creatinine must be less than or equal to 1.4 mg/dL or the creatinine clearance must be greater than or equal to 50 ml/min as measured from a 24-hour urine collection.
Patients should not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
EXCLUSION CRITERIA:
Patients whose serum neutralizes LMB-2 in tissue culture, due either to anti-toxin or anti-mouse-lgG antibodies. No patient whose serum neutralizes greater than 75% of the activity of 1 micro g/mL of LMB-2 will be treated.
Patients who received LMB-2 on another trial.
Monoclonal antibody therapy within 12 weeks of enrollment.
Patients who are pregnant or breast-feeding.
Patients who are HIV positive.
Patients who have hepatitis C or chronic liver disease. Patients would not be excluded for hepatitis B surface antigen positivity if on Lamivudine.
Patients receiving warfarin for anticoagulation.
Patients with a left ventricular ejection fraction of less than the institutional lower limit of normal.
Patients with a DLCO less than 55% of normal or an FEV1 less than 60% of normal.
Patients who have active cancer requiring treatment.
Contacts and Locations More Information
| Responsible Party: | Robert J. Kreitman, M.D./National Cancer Institute, National Institutes of Health |
| ClinicalTrials.gov Identifier: | NCT00077922 History of Changes |
| Obsolete Identifiers: | NCT00080821 |
| Other Study ID Numbers: | 040121, 04-C-0121 |
| Study First Received: | February 12, 2004 |
| Last Updated: | December 14, 2011 |
| Health Authority: | United States: Federal Government |
|
LMB-2 Chronic Lymphocytic Leukemia CLL Immunotoxin Oncology |
Lymphocytes Hematological Disease Monoclonal Antibody Neutralizing Antibodies |
|
Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Leukemia, B-Cell Lymphoproliferative Disorders |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Immunotoxins Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
