Expired Study
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Bethesda, Maryland 20892


Purpose:

RATIONALE: Monoclonal antibodies such as siplizumab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. PURPOSE: This phase I trial is studying the side effects, best way to give, and best dose of siplizumab in treating patients with lymphoproliferative disorders.


Study summary:

OBJECTIVES: Primary - Determine the maximum tolerated dose of siplizumab (MEDI-507) in patients with CD2-positive lymphoproliferative disorders. - Determine the safety and tolerability of this drug in these patients. Secondary - Determine the time to MEDI-507 saturation of CD2-binding sites in peripheral blood and tumor aspirates of these patients. - Determine the serum pharmacokinetics of this drug in these patients. - Determine the time to T-cell and natural killer cell depletion and recovery in patients after treatment with this drug. - Determine the antitumor activity of this drug, in terms of response rate, time to progression, and overall survival, in these patients. OUTLINE: This is an open-label, dose-escalation study. Patients receive siplizumab (MEDI-507) IV over 4 hours on days 1 and 2 every 2 weeks for 16 weeks OR on days 1-3 every 2 weeks for 16 weeks OR on days 1 and 14, then weekly for 16 weeks in the absence of disease progression or unacceptable toxicity. Patients with a positive treatment response (e.g., stable disease, minor response, partial response, or complete response) after 16 weeks of treatment may continue to receive MEDI-507 as above in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of MEDI-507 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After completion of treatment, patients are followed at 30 days and then every 3 months for 1 year. PROJECTED ACCRUAL: A total of 88 patients will be accrued for this study.


Criteria:

DISEASE CHARACTERISTICS: - Histologically confirmed lymphoproliferative disorder, including the following types: - Adult T-cell leukemia - No smoldering leukemia - Cutaneous T-cell lymphoma - All stages, excluding stage Ia - Patients with stage Ib, II, or III disease must have failed at least 1 prior standard therapy regimen - Peripheral T-cell lymphoma - Stage I-IV - Disease progression after standard chemotherapy - Large granular lymphocyte leukemia meeting the following criteria: - Must have 1 of the following: - Myelosuppression based on at least 1 of the following laboratory values: - Granulocyte count no greater than 1,500/mm^3 - Platelet count no greater than 75,000/mm^3 - Hemoglobin no greater than 10 g/dL - Requirement for hematopoietic support (e.g., transfusion or colony-stimulating factors, including filgrastim [G-CSF], interleukin-11, or epoetin alfa) to maintain blood levels or control systemic symptoms (e.g., fever, night sweats, or weight loss) - Disease unresponsive to 1 prior therapy regimen - Monoclonal and polyclonal forms of disease allowed - CD2-positive by immunohistochemistry - At least 30% of tumor cells must express CD2 - Measurable or evaluable disease - No history of CNS disease PATIENT CHARACTERISTICS: Age - 18 and over Performance status - Karnofsky 70-100% Life expectancy - More than 2 months Hematopoietic - See Disease Characteristics - Granulocyte count at least 1,000/mm^3* - Platelet count at least 50,000/mm^3* NOTE: *Requirement waived for patients with large granular lymphocyte leukemia Hepatic - SGOT and SGPT ≤ 2.0 times upper limit of normal (ULN) (5 times ULN for patients with Gilbert's syndrome) - Bilirubin ≤ 2.0 mg/dL (3.5 times ULN for patients with Gilbert's syndrome) - Hepatitis B surface antigen negative - No positive antibodies to hepatitis C virus Renal - Creatinine ≤ 1.5 mg/dL OR - Creatinine clearance > 60 mL/ min by 24-hour urine collection Cardiovascular - No myocardial infarction within the past 6 months - No uncontrolled hypertension within the past 6 months - No stroke or transient ischemic attack within the past 6 months Pulmonary - Oxygen saturation level at least 90% by pulse oximetry - No respiratory insufficiency requiring oxygen therapy Other - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - HIV negative - Symptomatic cytomegalovirus (CMV) negative or CMV PCR ≤ 1000 copies - No history of significant adverse events related to previously administered monoclonal antibody - No active infection requiring systemic anti-infective therapy - No physical or general medical illness that would increase risk to the patient - No psychological or behavioral condition that would increase risk to the patient or preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy - At least 30 days since prior monoclonal antibody therapy - No prior siplizumab (MEDI-507) - No other concurrent monoclonal antibody therapies - No other concurrent biologic response modifier therapy - No concurrent gamma globulin - Concurrent G-CSF, epoetin alfa, and interleukin-11 allowed for large granular lymphocyte leukemia Chemotherapy - See Disease Characteristics - At least 3 weeks since prior cytotoxic chemotherapy and recovered - No concurrent FDA-approved or investigational cancer chemotherapeutic agents Endocrine therapy - At least 3 weeks since prior prolonged cytolytic steroid therapy and recovered - No concurrent steroids Radiotherapy - Not specified Surgery - At least 3 weeks since prior surgery and recovered Other - At least 30 days since other prior investigational anticancer drugs - No other concurrent investigational anticancer drugs


NCT ID:

NCT00075361


Primary Contact:

Principal Investigator
Thomas A. Waldmann, MD
NCI - Metabolism Branch;MET


Backup Contact:

N/A


Location Contact:

Bethesda, Maryland 20892
United States



There is no listed contact information for this specific location.

Site Status: N/A


Data Source: ClinicalTrials.gov

Date Processed: June 25, 2018

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