Ignite Creation Date:
2024-05-05 @ 11:34 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00077922
Status:
COMPLETED
Last Update Posted:
2018-01-23
First Post:
2004-02-12
Brief Title:
Anti-TacFv-PE38 LMB-2 to Treat Chronic Lymphocytic Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase II Clinical Trial of Anti-TacFv-PE38 LMB-2 Immunotoxin for Treatment of CD25 Positive Chronic Lymphocytic Leukemia
Status:
COMPLETED
Status Verified Date:
2017-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 cluster of differentiation 25 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 computed tomography 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 National Institutes of Health 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
Blood draws Blood is drawn before during and after each LMB-2 infusion to measure blood levels of the drug evaluate its effects on the cancer cells and monitor side effects Blood tests are also done before and during each cycle to determine how the immune system is interacting with the drug
Disease evaluations Patients undergo a physical examination blood tests chest x-ray and EKG before each treatment cycle and at follow-up visits With the patients permission CT scans echocardiogram and bone marrow biopsies may be repeated before some treatment cycles if these tests prove useful in evaluating the disease response to LMB-2
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
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 computed tomography 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 National Institutes of Health 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
Blood draws Blood is drawn before during and after each LMB-2 infusion to measure blood levels of the drug evaluate its effects on the cancer cells and monitor side effects Blood tests are also done before and during each cycle to determine how the immune system is interacting with the drug
Disease evaluations Patients undergo a physical examination blood tests chest x-ray and EKG before each treatment cycle and at follow-up visits With the patients permission CT scans echocardiogram and bone marrow biopsies may be repeated before some treatment cycles if these tests prove useful in evaluating the disease response to LMB-2
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
Detailed Description:
Background
It is estimated that 30-50 of patients with CLL have tumors that express cluster of differentiation 25 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 National Cancer Institute NCI found that the maximum tolerated dose MTD of LMB-2 was 40 microgKg IV given every other day for 3 doses every other day 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 complete response CR 3 partial response PRs and 3 other patients had PRs 1 cutaneous T-cell lymphoma CTCL 1 healthy donor HD 1 acute T-cell leukemialymphoma 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-TacFv-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 less than 11 gdl
or platelets less than 100000ul
Patients must have progression following purine analog or alkylating agent
Labs required alanine aminotransferase ALT and aspartate aminotransferase AST less than or equal to 25- time upper limit
albumin greater than or equal to 3 bilirubin less than equal to 22 unless unconjugated greater than or equal to 80
and creatinine less than or equal to 14 unless creatinine clearance greater than or equal to 50 mlmin
Design
Patients receive LMB-2 40 ugKg 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
It is estimated that 30-50 of patients with CLL have tumors that express cluster of differentiation 25 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 National Cancer Institute NCI found that the maximum tolerated dose MTD of LMB-2 was 40 microgKg IV given every other day for 3 doses every other day 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 complete response CR 3 partial response PRs and 3 other patients had PRs 1 cutaneous T-cell lymphoma CTCL 1 healthy donor HD 1 acute T-cell leukemialymphoma 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-TacFv-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 less than 11 gdl
or platelets less than 100000ul
Patients must have progression following purine analog or alkylating agent
Labs required alanine aminotransferase ALT and aspartate aminotransferase AST less than or equal to 25- time upper limit
albumin greater than or equal to 3 bilirubin less than equal to 22 unless unconjugated greater than or equal to 80
and creatinine less than or equal to 14 unless creatinine clearance greater than or equal to 50 mlmin
Design
Patients receive LMB-2 40 ugKg 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-C-0121 | None | None | None |