Ignite Creation Date:
2024-05-05 @ 11:33 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00076180
Status:
COMPLETED
Last Update Posted:
2019-01-11
First Post:
2004-01-14
Brief Title:
Hu-Mik-beta1 to Treat T-Cell Large Granular Lymphocytic Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase I Open-Label Single-Dose Study of Humanized Mik-Beta-1 Monoclonal Antibody Directed Toward the IL-2RIL-15R-Beta Subunit CD122 in T Cell Large Granular Lymphocytic Leukemia
Status:
COMPLETED
Status Verified Date:
2019-01-09
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 use of the humanized Mik-beta-1 Hu-Mik-beta1 antibody in patients with T-cell large granular lymphocytic leukemia T-LGL Patients with T-LGL often have reduced white blood cells red blood cells and platelets and increased numbers of abnormal cells called large granular lymphocytes LGLs Patients may have recurrent infections anemia or abnormal bleeding Hu-Mik-beta1 attaches to LGL cells and blocks the action of growth factors called interleukins that stimulate LGL growth Blocking these interleukins may stop T-LGL leukemia cells from growing This study will determine the dose and frequency of treatment with Hu-Mik-SqrRoot 1 that can safely be given to patients to coat the surface of their leukemic cells with antibody determine how long the antibody lasts in the blood after injection and examine the side effects and possible benefits of the drug in these patients
Patients age 18 or older with T-LGL may be eligible for this study Candidates will be screened with a medical history and physical examination review of pathology studies skin biopsy evaluation of rheumatoid arthritis if present chest x-ray computerized tomography CT scans and other imaging studies as needed bone marrow biopsy and blood and urine tests
Participants will receive a single dose of Hu-Mik-beta1 by a 90-minute infusion through a vein Groups of patients will be treated with increasing doses 05 10 and 15 mgkg of the antibody Patients who develop serious drug side effects are taken off the study The treatment requires a 3- to 4-day hospital stay In addition to Hu-Mik-SqrRoot 1 treatment patients will undergo the following tests and procedures
Collection of blood for 8 days following the dose of Hu-Mik-beta1 to measure blood levels of the antibody
Follow-up visits of 1 to 2 days at 22 29 and 43 days after the dose of the antibody and then every 3 months for a total of 9 months
Bone marrow aspirate and biopsy if one has not been done within 6 weeks before entering the study and a repeat biopsy if complete remission of T-LGL is achieved after completing treatment For the biopsy an area of the hip is numbed and a special needle is used to draw bone marrow from the hipbone
Imaging studies such as chest x-ray and CT scan of the body after completing treatment if the screening scans showed abnormalities due to the T-LGL leukemia
Lymph node biopsy in individuals with enlarged superficial lymph nodes due to T-LGL leukemia to see if the treatment is reaching the leukemia in the lymph nodes
There may or may not be a direct benefit from participating in this study However the results may help in the treatment of future patients
Patients age 18 or older with T-LGL may be eligible for this study Candidates will be screened with a medical history and physical examination review of pathology studies skin biopsy evaluation of rheumatoid arthritis if present chest x-ray computerized tomography CT scans and other imaging studies as needed bone marrow biopsy and blood and urine tests
Participants will receive a single dose of Hu-Mik-beta1 by a 90-minute infusion through a vein Groups of patients will be treated with increasing doses 05 10 and 15 mgkg of the antibody Patients who develop serious drug side effects are taken off the study The treatment requires a 3- to 4-day hospital stay In addition to Hu-Mik-SqrRoot 1 treatment patients will undergo the following tests and procedures
Collection of blood for 8 days following the dose of Hu-Mik-beta1 to measure blood levels of the antibody
Follow-up visits of 1 to 2 days at 22 29 and 43 days after the dose of the antibody and then every 3 months for a total of 9 months
Bone marrow aspirate and biopsy if one has not been done within 6 weeks before entering the study and a repeat biopsy if complete remission of T-LGL is achieved after completing treatment For the biopsy an area of the hip is numbed and a special needle is used to draw bone marrow from the hipbone
Imaging studies such as chest x-ray and CT scan of the body after completing treatment if the screening scans showed abnormalities due to the T-LGL leukemia
Lymph node biopsy in individuals with enlarged superficial lymph nodes due to T-LGL leukemia to see if the treatment is reaching the leukemia in the lymph nodes
There may or may not be a direct benefit from participating in this study However the results may help in the treatment of future patients
Detailed Description:
Background
T cell large granular lymphocyte T-LGL leukemia is a chronic lymphoproliferative disorder associated with granulocytopenia anemia andor thrombocytopenia
Although agents such as cyclosporine and methotrexate have shown activity in T-LGL treatment of T-LGL has remained largely undefined and symptomatic
The shared IL-2RIl-15R Beta receptor CD122 is over expressed on T-LGL cells and may stimulate growth T-LGL cells through its interaction with IL-15
Hu-Mik-Beta1 is a humanized monoclonal antibody that binds to IL-2RIL-15R Beta
Hu-Mik-Beta1 may inhibit the growth and exert cytotoxic activity against T-LGL cells
Objectives
To determine the dose-limiting toxicity DLT and the maximum tolerated dose MTD of Hu-Mik-Beta1 when administered to patients with T-LGL
To determine the dose of Hu-Mik-Beta1 required to saturate IL-2RIL-15R Beta CD122 on -T-LGL cells in the peripheral blood
To determine the pharmacokinetics and serum die-away curve of Hu-Mik-Beta1
To provide preliminary information on the clinical response following single dose administration of Hu-MiK-Beta1 in patients with CD122 expressing T-LGL leukemia
Eligibility
--T cell large granular lymphocyte leukemia T-LGL
Patients must have a granulocyte count of less than 1000microL or hemoglobin less than 10 gmdL or be transfusion dependent or platelets less than 100000 microL or any combination of these unless receiving a hematopoietic growth factor
T-LGL cell count greater than or equal to 1000microL CD3 plusCD8 plususually CD57 plus by flow cytometry
Patients may be receiving a stable dose of a hematopoietic growth factor
Design
Cohorts of 3 patients each will be treated with a single intravenous dose of Hu-Mik-Beta1 at 05 10 or 15 mgkg
Patients will be observed for adverse events for 6-weeks
Detailed pharmacokinetic studies and determination of CD122 receptor saturation will be performed
Response will be evaluated using hematological flow cytometry molecular and clinical evaluations
An additional 3 patients will be accrued at the highest dose or MTD to aid in design of a Phase II trial
Patients participating in Phase I will also be eligible to participate in Phase II
T cell large granular lymphocyte T-LGL leukemia is a chronic lymphoproliferative disorder associated with granulocytopenia anemia andor thrombocytopenia
Although agents such as cyclosporine and methotrexate have shown activity in T-LGL treatment of T-LGL has remained largely undefined and symptomatic
The shared IL-2RIl-15R Beta receptor CD122 is over expressed on T-LGL cells and may stimulate growth T-LGL cells through its interaction with IL-15
Hu-Mik-Beta1 is a humanized monoclonal antibody that binds to IL-2RIL-15R Beta
Hu-Mik-Beta1 may inhibit the growth and exert cytotoxic activity against T-LGL cells
Objectives
To determine the dose-limiting toxicity DLT and the maximum tolerated dose MTD of Hu-Mik-Beta1 when administered to patients with T-LGL
To determine the dose of Hu-Mik-Beta1 required to saturate IL-2RIL-15R Beta CD122 on -T-LGL cells in the peripheral blood
To determine the pharmacokinetics and serum die-away curve of Hu-Mik-Beta1
To provide preliminary information on the clinical response following single dose administration of Hu-MiK-Beta1 in patients with CD122 expressing T-LGL leukemia
Eligibility
--T cell large granular lymphocyte leukemia T-LGL
Patients must have a granulocyte count of less than 1000microL or hemoglobin less than 10 gmdL or be transfusion dependent or platelets less than 100000 microL or any combination of these unless receiving a hematopoietic growth factor
T-LGL cell count greater than or equal to 1000microL CD3 plusCD8 plususually CD57 plus by flow cytometry
Patients may be receiving a stable dose of a hematopoietic growth factor
Design
Cohorts of 3 patients each will be treated with a single intravenous dose of Hu-Mik-Beta1 at 05 10 or 15 mgkg
Patients will be observed for adverse events for 6-weeks
Detailed pharmacokinetic studies and determination of CD122 receptor saturation will be performed
Response will be evaluated using hematological flow cytometry molecular and clinical evaluations
An additional 3 patients will be accrued at the highest dose or MTD to aid in design of a Phase II trial
Patients participating in Phase I will also be eligible to participate in Phase II
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
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 |
|---|---|---|---|
| 04-C-0089 | None | None | None |