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Anti-Tac for Treatment of Leukemia Clinical Trials References presented on Clinical Trials Search is not intended to be a substitute for proven healthcare advice, trips or professional assistance by using a real medical. We aren't mDs. Always confer with your physician about Anti-Tac for Treatment of Leukemia conditions. Clinical Trials Search.org is a website devoted to listing clinical research studies in human subjects. Anti-Tac for Treatment of Leukemia Clinical research trials and Anti-Tac for Treatment of Leukemia medical trials take place in hundreds of localities across the U.S.. A clinical trial or clinical study is a research project with human volunteer subjects. Clinical drug trials and pharmaceutical clinical trials usually evaluate the effectualness of new does drugs. The purpose of the studies / projects is to solve specific human health questions. Clinical trials are a popular way for physicians, government agencies, and private sector companies to discover treatments for all sorts of conditions, such as Anti-Tac for Treatment of Leukemia. Anti-Tac for Treatment of Leukemia Clinical Trials and other clinical trials permit volunteers to access healthcare treatment choices before they are available to the general public. Some times the subjects recieve professional assistance for without cost, and every now and again they are compensated for their time. Sometimes there is a cost for a Anti-Tac for Treatment of Leukemia clinical trial. Subjects often receive the most expert healthcare possible for their Anti-Tac for Treatment of Leukemia condition. Risks are a reality, nevertheless, and could include additional or frequent dr. calls, healthcare dangers (perhaps life-jeopardising), and/or the treatment being ineffective. Trials are federally governed with stern guidelines to protect clinical trials subjects.
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Home > "A" Clinical Trials Conditions > Anti-Tac for Treatment of Leukemia  Anti-Tac for Treatment of Leukemia
Anti-Tac for Treatment of Leukemia
For Condition: HTLV-I Infection,T Cell Leukemia
Status: Recruiting
Sponsor(s): National Cancer Institute (NCI) ,
Synopsis: The purpose of the study is to determine: (1) the toxicity and maximum tolerated dose (MTD) of humanized anti-Tac (daclizumab), (Zenapax® (Registered Trademark)) in patients with ATL; (2) to define the dose of Zenapax® (Registered Trademark) required to saturate IL-2R alpha in patients with ATL; (3) determine the clinical response to humanized (Hu) anti-Tac (Zenapax® (Registered 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 represents an extension of Metabolism Branch 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 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 will be treated with escalating doses of Zenapax® (Registered Trademark) between groups in the Clinical Center of the NIH. Groups of patients will receive sufficient Zenapax® (Registered Trademark) to yield saturation of the IL-2 receptor for a period of 17 weeks. Following an initial loading dose, the responding patients will receive subsequent doses at week 2 and then at 3 week intervals for a total of 6 doses. Clinical response will be 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 FACS analysis using two fluorochrome-labeled non-crossreacting antibodies to the IL-2 receptor, anti-Tac and 7G7/B6, as well as antibodies to CD3, CD4, CD7, and CD8. Furthermore, responses will be evaluated in patients with leukemia by Southern blot analysis of the arrangement of the T-cell receptor genes and HTLV-I integration. Finally, in select patients, to define the pharmacokinetics of the therapeutic antibody, we plan to monitor the serum levels of the infused Hu-anti-Tac (Zenapax® (Registered 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. In a subsequent addition to this protocol, we will propose that patients not manifesting a remission with Zenapax® (Registered Trademark) alone will cross over to a therapeutic regimen that includes saturating doses of Zenapax® (Registered Trademark) as well as additional agents directed toward ATL (e.g., zidovudine (AZT)/IFN). We also plan a future clinical trial where we will evaluate the efficacy and toxicity in ATL patients of saturating doses of Zenapax® (Registered Trademark) as compared to identical doses of Zenapax® (Registered Trademark) given in association with (90)Y-armed 7G7/B6, a non-competing antibody to IL-2R alpha or in combination with chemotherapy.
Details: The purpose of the study is to determine: (1) the toxicity and maximum tolerated dose (MTD) of humanized anti-Tac (daclizumab, Zenapax TM) in patients with ATL; (2) to define the dose of Zenapax® (Registered Trademark) required to saturate IL-2R alpha in patients with ATL; (3) determine the clinical response to humanized (Hu) anti-Tac (Zenapax® (Registered 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 represents an extension of Metabolism Branch 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 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 will be treated with escalating doses of Zenapax® (Registered Trademark) between groups in the Clinical Center of the NIH. Groups of patients will receive sufficient Zenapax® (Registered Trademark) to yield saturation of the IL-2 receptor for a period of 17 weeks. Following an initial loading dose, the responding patients will receive subsequent doses at week 2 and then at 3 week intervals for a total of 6 doses. Clinical response will be 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 FACS analysis using two fluorochrome-labeled non-crossreacting antibodies to the IL-2 receptor, anti-Tac and 7G7/B6, as well as antibodies to CD3, CD4, CD7, and CD8. Furthermore, responses will be evaluated in patients with leukemia by Southern blot analysis of the arrangement of the T-cell receptor genes and HTLV-I integration. Finally, in select patients, to define the pharmacokinetics of the therapeutic antibody, we plan to monitor the serum levels of the infused Hu-anti-Tac (Zenapax® (Registered 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. In a subsequent addition to this protocol, we will propose that patients not manifesting a remission with Zenapax® (Registered Trademark) alone will cross over to a therapeutic regimen that includes saturating doses of Zenapax® (Registered Trademark) as well as additional agents directed toward ATL (e.g., zidovudine (AZT)/IFN). We also plan a future clinical trial where we will evaluate the efficacy and toxicity in ATL patients of saturating doses of Zenapax® (Registered Trademark) as compared to identical doses of Zenapax® (Registered Trademark) given in association with (90)Y-armed 7G7/B6, a non-competing antibody to IL-2R alpha or in combination with chemotherapy.
Eligibility:
Study Type: Interventional, Treatment, Safety/Efficacy
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: INCLUSION CRITERIA Patients diagnosed with any stage of HTLV-I-associated adult T-cell leukemia. Patients must have serum antibodies directed to HTLV-I. All patients must have a histologically confirmed diagnosis of adult T-cell leukemia/lymphoma. At least 5 percent of each patient's peripheral blood, lymph node, pulmonary or dermal malignant cells must react with the anti-Tac mAb as determined by immunofluorescent staining or, alternatively, the serum-soluble IL-2 receptor levels must be greater than 1,000 units/ml. All stages of Tac-expressing adult T-cell leukemia are eligible including smoldering, chronic, lymphoma or acute ATL. Patients must have measurable disease. All patients with greater than 5 percent abnormal (i.e., Tac homogenous strongly expressing) PBMC in the peripheral blood will be deemed to have measurable disease. The patient must have a granulocyte count of at least 500/mm(3) and a platelet count of 25,000/mm(3). Patients must have a creatinine of less than 3.0 mg/dl. Patients must have a Karnofsky performance score of greater than 60 percent. ATL patients without, as well as those with, previous chemotherapy will be eligible for inclusion in the study. Patients with previous therapy with a monoclonal antibody including anti-Tac will be eligible for the study provided that they do not have a positive HAHA (human antibody to humanized anti-Tac) value (i.e., such patients must have a value greater than 250 ng/ml). Omission of cytotoxic chemotherapy for ATL for 3 weeks prior to entry into the trial is required. However, patients receiving corticosteroids will not be excluded. Patients must have a life expectancy of greater than 2 months. Eligible patients must be greater than or equal to 10 years old. There is no upper age limit. Patients over the age of 18 years must be able to understand and sign an Informed Consent form. Eligible minors greater than 10 years old must give assent to participate in this study. EXCLUSION CRITERIA: Patients with symptomatic central nervous system disease that is due to the adult T-cell leukemia will be excluded. However, patients that have both ATL and another HTLV-I-associated disease, tropical spastic paraparesis (TSP), will be included. Tac-expressing T cells may be present in the CSF as long as the patient does not have symptomatic CNS disease. Pregnant and/or nursing patients are not eligible for the study. HIV positive patients are excluded from the study. Patients with SGOT or SGPT values 5.0-fold greater than the upper limit of normal or bilirubin greater than 2.9 mg/dl will be excluded.
Total Enrollment: 44
Location and Contact Information:
National Cancer Institute (NCI) *Recruiting*
Bethesda, Maryland, 20892
United States
Recruiting Wendy Gao 3014021898
Additional Information:
Study ID Numbers: 000030; 00-C-0030
Study Start Date: December 10, 1999
Record last reviewed: November 1, 2003
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00001941
Other Htlv-I Infection Studies:
1. Phase I Study of Anti-Tac(Fv)-PE38 (LMB-2), a Recombinant Single-Chain Immunotoxin for Treatment of Tac-Expressing Malignancies
2. Anti-Tac for Treatment of Leukemia
3. Phase I Study of T-Cell Large Granular Lymphocytic Leukemia Using the MIK-Beta-1 Monoclonal Antibody Directed Toward the IL-2R-Beta Subunit
4. Phase I/II Study of Tac-Expressing Adult T-Cell Leukemia (ATL) with Yttrium-90 (90Y)-Radiolabeled Humanized Anti-Tac Monoclonal Antibody and Calcium-DTPA
Related Studies:
Other HTLV-I Infection Clinical Trials
Other Maryland Clinical Trials
Other Bethesda Clinical Trials
Anti-Tac for Treatment of Leukemia
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