Ignite Creation Date:
2024-05-05 @ 11:22 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001941
Status:
COMPLETED
Last Update Posted:
2012-08-20
First Post:
2000-01-18
Brief Title:
Anti-Tac for Treatment of Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase III Study of the Efficacy and Toxicity of Humanized Anti-Tac ZenapaxTrademark in the Therapy of Tac-Expressing Adult T-Cell Leukemia
Status:
COMPLETED
Status Verified Date:
2012-08
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:
The purpose of the study was to determine 1 the toxicity and maximum tolerated dose MTD of humanized anti-Tac daclizumab ZenapaxRegistered Trademark in patients with adult T-cell leukemialymphoma ATL 2 to define the dose of ZenapaxRegistered Trademark required to saturate interleukin 2 receptor alpha IL-2R alpha in patients with ATL 3 determine the clinical response to humanized Hu anti-Tac ZenapaxRegistered Trademark of patients with Tac-expressing adult T-cell leukemia and 4 determine the serum dieaway curve pharmacokinetics of infused humanized Hu-anti-Tac in patients who have ATL This study represented an extension of Metabolism Branch National Cancer Institute NCI protocols utilizing modifications of the original murine anti-Tac monoclonal antibody mAb developed by our group for the treatment of ATL The scientific basis for these therapeutic studies is that the leukemic cells of patients with ATL express abnormally high levels of the Tac antigen IL-2R alpha on their surface whereas resting normal cells including normal T-cells of the patients do not One presumed mode of action of Hu-anti-Tac in the treatment of ATL involves the interruption of the interaction of interleukin 2 IL-2 with its growth factor receptor To be effective in this goal we must maintain saturation of the IL-2 receptors IL-2R with humanized anti-Tac thereby preventing IL-2 mediated proliferation and yielding cytokine deprivation and apoptotic cell death of the leukemic cells Eligible patients with ATL were treated with escalating doses of ZenapaxRegistered Trademark between groups in the Clinical Center of the National Institutes of Health NIH Groups of patients received sufficient ZenapaxRegistered Trademark to yield saturation of the IL-2 receptor for a period of 17 weeks Clinical response was evaluated using routine immunological and clinical evaluation and by monitoring the saturation of the IL-2R and the absolute number of residual circulating malignant cells by fluorescence activated cell sorting FACS analysis using two fluorochrome-labeled non-crossreacting antibodies to the IL-2 receptor anti-Tac and 7G7B6 as well as antibodies to cluster of differentiation 3 CD3 cluster of differentiation 4 CD4 cluster of differentiation 7 CD7 and cluster of differentiation 8 CD8 Furthermore responses were evaluated in patients with leukemia by Southern blot analysis of the arrangement of the T-cell receptor genes and human T-lymphotropic virus type 1 HTLV-I integration Finally in select patients to define the pharmacokinetics of the therapeutic antibody had planned to monitor the serum levels of the infused Hu-anti-Tac ZenapaxRegistered Trademark as a function of time This study is an essential element of our program involving IL-2R-directed therapeutic studies If as anticipated the therapy with humanized anti-Tac yields some partial and complete remissions in patients with ATL we will propose that it be used as a single agent for patients with smoldering and chronic ATL and in association with chemotherapeutic agents to provide a novel approach for the treatment of acute and lymphoma forms of ATL We also plan a future clinical trial where tentative plans also had been made to evaluate the efficacy and toxicity in ATL patients of saturating doses of ZenapaxRegistered Trademark as compared to identical doses of ZenapaxRegistered Trademark given in association with 90Y-armed 7G7B6 a non-competing antibody to IL-2R alpha or in combination with chemotherapy
Detailed Description:
Background
Human T-lymphotropic virus type 1 HTLV-1-associated adult T cell leukemialymphoma ATL is an aggressive lymphoproliferative disorder
Chemotherapy has had limited impact on survival
The interleukin 2 receptor alpha IL-2R alpha CD25 is over expressed on ATL cells and the smoldering and chronic stages of ATL are often interleukin 2 IL-2 dependent
The monoclonal antibody daclizumab Zenapax inhibits interleukin 2 IL-2 binding to its receptor
It is hypothesized that daclizumab may inhibit ATL growth
Objectives
To determine the toxicity and maximum tolerated dose MTD of humanized anti-Tac daclizumab Zenapax in patients with ATL
To define the dose of Zenapax required to saturate IL-2R alpha in patients with ATL
To determine the clinical response to humanized Hu anti-Tac Zenapax of patients with Tac-expressing smoldering and chronic stage adult T cell leukemia
To determine the serum dieaway curve pharmacokinetics of infused humanized Hu - anti - Tac in patients who have ATL
Eligibility
Smoldering and chronic stage HTLV-1-associated adult T cell leukemia
At least 5 percent of malignant cells in the peripheral blood or lymph nodes must react with the anti-Tac CD25 antibody
Age greater than or equal to 10-years-old
Patients must have measurable disease
Patients with and without prior treatment
Patients must have a granulocyte count of greater than or equal to 500micro L
platelets greater than or equal to 25000micro L
and creatinine less than 30 gmdL
Design
Phase I patients on cohorts 1-4 received the following cohort 1 2 mgkg over 60 minutes intravenously on days 1 and 2 cohort 2 4 mgkg over 90 minutes intravenously on day 1 single dose cohort 3 6 mgkg over 90 minutes intravenously on day 1 single dose and cohort 4 8 mgkg over 90 minutes intravenously on day 1 single dose
Patients with smoldering or chronic stage ATL will be treated with intravenous daclizumab 8 mgkg on day 0 and weeks 2 5 8 11 and 14
Patients achieving a response will continue on treatment with daclizumab 8 mgkg every 3 weeks for up to 24 months
Patients achieving a complete response CR will continue on treatment with daclizumab 8mgkg every 3 weeks for up to 24 months
Patients achieving a partial response PR will be maintained on daclizumab 8 mgkg administered every 3 weeks provided the PR is maintained and no serious adverse event or toxicity related to daclizumab therapy is observed
Human T-lymphotropic virus type 1 HTLV-1-associated adult T cell leukemialymphoma ATL is an aggressive lymphoproliferative disorder
Chemotherapy has had limited impact on survival
The interleukin 2 receptor alpha IL-2R alpha CD25 is over expressed on ATL cells and the smoldering and chronic stages of ATL are often interleukin 2 IL-2 dependent
The monoclonal antibody daclizumab Zenapax inhibits interleukin 2 IL-2 binding to its receptor
It is hypothesized that daclizumab may inhibit ATL growth
Objectives
To determine the toxicity and maximum tolerated dose MTD of humanized anti-Tac daclizumab Zenapax in patients with ATL
To define the dose of Zenapax required to saturate IL-2R alpha in patients with ATL
To determine the clinical response to humanized Hu anti-Tac Zenapax of patients with Tac-expressing smoldering and chronic stage adult T cell leukemia
To determine the serum dieaway curve pharmacokinetics of infused humanized Hu - anti - Tac in patients who have ATL
Eligibility
Smoldering and chronic stage HTLV-1-associated adult T cell leukemia
At least 5 percent of malignant cells in the peripheral blood or lymph nodes must react with the anti-Tac CD25 antibody
Age greater than or equal to 10-years-old
Patients must have measurable disease
Patients with and without prior treatment
Patients must have a granulocyte count of greater than or equal to 500micro L
platelets greater than or equal to 25000micro L
and creatinine less than 30 gmdL
Design
Phase I patients on cohorts 1-4 received the following cohort 1 2 mgkg over 60 minutes intravenously on days 1 and 2 cohort 2 4 mgkg over 90 minutes intravenously on day 1 single dose cohort 3 6 mgkg over 90 minutes intravenously on day 1 single dose and cohort 4 8 mgkg over 90 minutes intravenously on day 1 single dose
Patients with smoldering or chronic stage ATL will be treated with intravenous daclizumab 8 mgkg on day 0 and weeks 2 5 8 11 and 14
Patients achieving a response will continue on treatment with daclizumab 8 mgkg every 3 weeks for up to 24 months
Patients achieving a complete response CR will continue on treatment with daclizumab 8mgkg every 3 weeks for up to 24 months
Patients achieving a partial response PR will be maintained on daclizumab 8 mgkg administered every 3 weeks provided the PR is maintained and no serious adverse event or toxicity related to daclizumab therapy is observed
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 |
|---|---|---|---|
| 00-C-0030 | None | None | None |