Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00011908
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2001-03-03
Brief Title:
Humanized LL2IGG to Treat Systemic Lupus Erythematosus
Sponsor:
National Institute of Arthritis and Musculoskeletal and Skin Diseases NIAMS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase I Clinical Trial of Immunotherapy With Humanized LL2 IgG Epratuzumab in Patients With Systemic Lupus Erythematosus
Status:
COMPLETED
Status Verified Date:
2003-01
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 examine the safety of a new genetically engineered antibody called hLL2 epratuzumab in patients with systemic lupus erythematosus SLE It will also evaluate whether hLL2 can lessen overall disease activity in SLE or kidney damage in patients with lupus nephritis
Patients 18 years of age and older with mild to moderately active SLE may be eligible for this study Candidates will be screened with blood and urine tests a chest X-ray electrocardiogram EKG tuberculin skin test and screening tests for certain cancers
All participants will receive weekly infusions of hLL2 for 4 weeks The drug is given through a catheter small plastic tube placed through a needle in an arm vein Each infusion takes about 2 hours after which the patient is observed in the clinic for 1 to 2 hours before being discharged from the clinic
The first 3 patients in the study will receive the lowest of three different doses used in the study If this dose is well tolerated the next 5 patients will receive a higher dose If the second dose is tolerated the last 5 patients will be given the highest dose If any serious problems are encountered at a dose patients in the next group will receive either the same or lower dose before being advanced to the next level Patients in the first group will continue taking prednisone at their regular dose All other patients will have their prednisone tapered gradually if their condition permits Patients who have a disease flare may have their prednisone increased for up to 2 weeks followed by a gradual taper If the flare is severe or does not respond to the increased prednisone the patient will be taken off the study and treated to control the disease
Patients will be evaluated at various intervals for up to 8 weeks after the last dose Several of the screening tests will be repeated throughout the study No more than 500 ml of blood-the equivalent of a single blood donation-will be collected during a 2-month period Participants may also be asked to undergo the following optional procedures before starting treatment 1 week after the last dose and 8 weeks after the last treatment dose
Bone marrow aspiration - to collect cells from the bone marrow The hip area is anesthetized and a special needle is used to draw bone marrow from the hipbone
Tonsil biopsy - The area to be biopsied is numbed with a local anesthetic and small pieces of tissue will be removed with a special type of forceps The procedure may be done under general anesthetic
Magnetic resonance imaging MRI of the abdomen - The patient lies on a table within a metal cylinder the MRI scanner for about 30 to 40 minutes while images are obtained with the use of a strong magnetic field and radio waves
Patients 18 years of age and older with mild to moderately active SLE may be eligible for this study Candidates will be screened with blood and urine tests a chest X-ray electrocardiogram EKG tuberculin skin test and screening tests for certain cancers
All participants will receive weekly infusions of hLL2 for 4 weeks The drug is given through a catheter small plastic tube placed through a needle in an arm vein Each infusion takes about 2 hours after which the patient is observed in the clinic for 1 to 2 hours before being discharged from the clinic
The first 3 patients in the study will receive the lowest of three different doses used in the study If this dose is well tolerated the next 5 patients will receive a higher dose If the second dose is tolerated the last 5 patients will be given the highest dose If any serious problems are encountered at a dose patients in the next group will receive either the same or lower dose before being advanced to the next level Patients in the first group will continue taking prednisone at their regular dose All other patients will have their prednisone tapered gradually if their condition permits Patients who have a disease flare may have their prednisone increased for up to 2 weeks followed by a gradual taper If the flare is severe or does not respond to the increased prednisone the patient will be taken off the study and treated to control the disease
Patients will be evaluated at various intervals for up to 8 weeks after the last dose Several of the screening tests will be repeated throughout the study No more than 500 ml of blood-the equivalent of a single blood donation-will be collected during a 2-month period Participants may also be asked to undergo the following optional procedures before starting treatment 1 week after the last dose and 8 weeks after the last treatment dose
Bone marrow aspiration - to collect cells from the bone marrow The hip area is anesthetized and a special needle is used to draw bone marrow from the hipbone
Tonsil biopsy - The area to be biopsied is numbed with a local anesthetic and small pieces of tissue will be removed with a special type of forceps The procedure may be done under general anesthetic
Magnetic resonance imaging MRI of the abdomen - The patient lies on a table within a metal cylinder the MRI scanner for about 30 to 40 minutes while images are obtained with the use of a strong magnetic field and radio waves
Detailed Description:
This is a pilot study to evaluate the safety and tolerance of hLL2 epratuzumab a humanized anti-CD22 monoclonal antibody in patients with systemic lupus erythematosus SLE
B-lymphocytes play a major role in initiating and maintaining the underlying immunopathological mechanisms of SLE In addition to producing autoantibodies they also serve as antigen presenting cells and are able to disrupt peripheral T lymphocyte tolerance Furthermore B lymphocyte depletion ameliorates disease activity in animal models of SLE Therefore targeted depletion of B-lymphocytes may be of therapeutic benefit in human SLE
hLL2 epratuzumab is a humanized monoclonal antibody that binds to CD22 a surface antigen expressed exclusively on B-lymphocytes Clinical studies in patients with B cell lymphomas have shown that epratuzumab is safe and well tolerated across a wide range of doses Although the exact mechanism is unknown indirect evidence suggests that the antibody is depleting target B lymphocytes Epratuzumab is made available by Immunomedics Inc and will be used under an investigator NIH-initiated IND
In this open-label Phase I study up to 20 patients with moderately active SLE may be enrolled Patients will be treated with weekly infusions of hLL2 in one of three different dosing groups 240 mgm2 360 mgm2 480 mgm2 for 4 weeks and followed for 8 weeks after the last dose
The primary objective is to determine the safety and tolerability of hLL2 in patients with SLE In addition to safety data clinical and laboratory data will also be collected for preliminary evaluation of the effectiveness of hLL2 in SLE and to assess the effect of hLL2 on B and T lymphocytes in the lymphoid organs and the peripheral blood If the treatment is safe and there is preliminary evidence of efficacy this regimen could be used in controlled trials in the future
B-lymphocytes play a major role in initiating and maintaining the underlying immunopathological mechanisms of SLE In addition to producing autoantibodies they also serve as antigen presenting cells and are able to disrupt peripheral T lymphocyte tolerance Furthermore B lymphocyte depletion ameliorates disease activity in animal models of SLE Therefore targeted depletion of B-lymphocytes may be of therapeutic benefit in human SLE
hLL2 epratuzumab is a humanized monoclonal antibody that binds to CD22 a surface antigen expressed exclusively on B-lymphocytes Clinical studies in patients with B cell lymphomas have shown that epratuzumab is safe and well tolerated across a wide range of doses Although the exact mechanism is unknown indirect evidence suggests that the antibody is depleting target B lymphocytes Epratuzumab is made available by Immunomedics Inc and will be used under an investigator NIH-initiated IND
In this open-label Phase I study up to 20 patients with moderately active SLE may be enrolled Patients will be treated with weekly infusions of hLL2 in one of three different dosing groups 240 mgm2 360 mgm2 480 mgm2 for 4 weeks and followed for 8 weeks after the last dose
The primary objective is to determine the safety and tolerability of hLL2 in patients with SLE In addition to safety data clinical and laboratory data will also be collected for preliminary evaluation of the effectiveness of hLL2 in SLE and to assess the effect of hLL2 on B and T lymphocytes in the lymphoid organs and the peripheral blood If the treatment is safe and there is preliminary evidence of efficacy this regimen could be used in controlled trials in the future
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| 01-AR-0108 | None | None | None |