Ignite Creation Date:
2024-05-05 @ 4:50 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00321555
Status:
COMPLETED
Last Update Posted:
2023-11-14
First Post:
2006-05-03
Brief Title:
LMB-2 to Treat Hairy Cell 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 CD25 Positive Hairy Cell Leukemia
Status:
COMPLETED
Status Verified Date:
2023-10
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:
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 patients permission these tests may be repeated before other cycles also
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 patients permission these tests may be repeated before other cycles also
Detailed Description:
Background About 80 of patients with hairy cell leukemia HCL have malignant cells that express cluster of differentiation 25 CD25 Tac or Interleukin-2 receptor alpha IL2Ra Normal resting B- and T-cells do not express CD25 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 intravenous IV given every other day for 3 doses QOD x3 The most common adverse events were transient fever hypoalbuminemia and transaminase elevations In that trial 4 of 4 patients with chemoresistant HCL had major responses including one complete CR and 3 partial remissions The patient with CR entered the trial transfusion dependent and now still has normal hemoglobin and platelet counts over 7 years later Because HCL is more frequently cluster of differentiation 22 CD22 than CD25 100 vs 80 HCL patients were subsequently treated with the anti-CD22 recombinant immunotoxin BL22 and no further HCL patients were treated with LMB-2 BL22 has induced 25 CRs out of 51 evaluable HCL patients LMB-2 may be useful in patients incompletely responding to BL22 because it may distribute more evenly through extravascular sites of disease Moreover BL22 but not LMB-2 has caused hemolytic uremic syndrome HUS in 7 patients 6 with HCL and several of these patients could benefit by LMB-2 Thus LMB-2 may be a useful and potentially lifesaving agent in patients who are unable to receive or who have not responded adequately to BL22
Objectives The purpose of this study is to determine the activity of anti-TacFv-PE38 LMB-2 in patients with CD25-expressing hairy cell leukemia HCL 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 Patients must have CD25 HCL cells by flow cytometry cytopenia or high circulating HCL count prior treatment with or inability to receive BL22 prior treatment with cladribine Eastern Cooperative Oncology Group ECOG Performance Status PS 0-2 at least 18 years old alanine aminotransferase ALT and aspartate aminotransferase AST grade 0-2 albumin grade 0-1 bilirubin less than or equal to 22 creatinine less than or equal to 14 or creatinine clearance greater than or equal to 50 lack of high levels of neutralizing antibodies lack of anti-CD25 Mab therapy for 12 weeks and other systemic treatment for 4 weeks no prior treatment with LMB-2 lack of other uncontrolled illness including 2nd malignancy no human immunodeficiency virus HIV or hepatitis C positivity no coumadin therapy left ventricular ejection fraction LVEF greater than or equal to 45 diffusing capacity of the lungs for carbon monoxide DLCO greater than or equal to 55 and forced expiratory volume 1 FEV1 greater than or equal to 60
Design Patients will receive LMB-2 at 40 microgKg every other day QOD x3 at intervals of at least 25 days for up to 6 cycles Retreatment is permitted in the absence of neutralizing antibodies or progressive disease Patients in CR may receive 2 consolidation cycles or 4 consolidation cycles if CR is with minimal residual disease
Dose level LMB-2 40 microgKg QOD x3
Expected Accrual 5-10 patientsyear total of 25 patients
Objectives The purpose of this study is to determine the activity of anti-TacFv-PE38 LMB-2 in patients with CD25-expressing hairy cell leukemia HCL 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 Patients must have CD25 HCL cells by flow cytometry cytopenia or high circulating HCL count prior treatment with or inability to receive BL22 prior treatment with cladribine Eastern Cooperative Oncology Group ECOG Performance Status PS 0-2 at least 18 years old alanine aminotransferase ALT and aspartate aminotransferase AST grade 0-2 albumin grade 0-1 bilirubin less than or equal to 22 creatinine less than or equal to 14 or creatinine clearance greater than or equal to 50 lack of high levels of neutralizing antibodies lack of anti-CD25 Mab therapy for 12 weeks and other systemic treatment for 4 weeks no prior treatment with LMB-2 lack of other uncontrolled illness including 2nd malignancy no human immunodeficiency virus HIV or hepatitis C positivity no coumadin therapy left ventricular ejection fraction LVEF greater than or equal to 45 diffusing capacity of the lungs for carbon monoxide DLCO greater than or equal to 55 and forced expiratory volume 1 FEV1 greater than or equal to 60
Design Patients will receive LMB-2 at 40 microgKg every other day QOD x3 at intervals of at least 25 days for up to 6 cycles Retreatment is permitted in the absence of neutralizing antibodies or progressive disease Patients in CR may receive 2 consolidation cycles or 4 consolidation cycles if CR is with minimal residual disease
Dose level LMB-2 40 microgKg QOD x3
Expected Accrual 5-10 patientsyear total of 25 patients
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 |
|---|---|---|---|
| 06-C-0150 | None | None | None |