Bethesda, Maryland 20892

  • Lymphoma

Purpose:

RATIONALE: Monoclonal antibodies, such as siplizumab and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine , cyclophosphamide, and doxorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from growing. Giving siplizumab together with combination chemotherapy and rituximab may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of siplizumab when given together with combination chemotherapy and rituximab in treating patients with T-cell or natural killer-cell non-Hodgkin lymphoma.


Study summary:

OBJECTIVES: Primary - Determine the toxicity of siplizumab in combination with dose-adjusted etoposide, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride, and rituximab (DA-EPOCH-R) in patients with chemotherapy-naive, CD2-expressing T-cell or natural killer (NK)-cell non-Hodgkin lymphoma. - Determine the maximum tolerated dose of siplizumab in combination with DA-EPOCH-R in these patients. Secondary - Determine, preliminarily, the anti-tumor activity of siplizumab and DA-EPOCH-R in these patients. - Determine the time course of B-, T-, and NK-cell depletion. - Determine the time course of B-, T- and NK-cell recovery. - Monitor EBV reactivation and its association with the development of EBV lymphoproliferative disease. OUTLINE: This is a dose-escalation study of siplizumab. Patients receive siplizumab IV on day 1. Patients also receive dose-adjusted rituximab IV on day 1; etoposide IV, vincristine sulfate IV, and doxorubicin IV over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline, during study, and after completion of study for pharmacokinetic studies via liquid chromatography mass spectrometry/mass spectrometry and ELIZA assay and for the evaluation of immunogenicity via human anti-humanized antibody assay. After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.


Criteria:

DISEASE CHARACTERISTICS: - Diagnosis of T-cell or natural killer (NK)-cell lymphoma confirmed by pathology or flow cytometry including, but not limited to, any of the following: - Peripheral T-cell lymphoma (not otherwise specified) - Gamma-delta hepatosplenic T-cell lymphoma - Subcutaneous panniculitis-like T-cell lymphoma - NK T-cell lymphoma - CD2-expressing disease confirmed by pathology or flow cytometry - At least 30% of the malignant cells must be CD2 positive - Chemotherapy-naive disease - No alk-positive anaplastic large cell lymphoma or precursor T-cell lymphoma - CNS involvement allowed PATIENT CHARACTERISTICS: - ANC ≥ 1,000/mm^3* - Platelet count ≥ 75,000/mm^3* - Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min* - Bilirubin < 2.0 mg/dL* unless due to Gilbert syndrome (unconjugated hyperbilirubinemia without other known cause) - AST and ALT ≤ 3 times upper limit of normal (ULN)* (≤ 6 times ULN for patients on hyperalimentation for whom these abnormalities are felt to be due to the hyperalimentation) - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - HIV negative - No active symptomatic ischemic heart disease, myocardial infarction, or congestive heart failure within the past year - No serious underlying medical condition or infection that would contraindicate study treatment NOTE: *Unless impairment due to respective organ involvement by tumor PRIOR CONCURRENT THERAPY: - See Disease Characteristics


NCT ID:

NCT00832936


Primary Contact:

Principal Investigator
Wyndham H. Wilson, MD, PhD
National Cancer Institute (NCI)


Backup Contact:

N/A


Location Contact:

Bethesda, Maryland 20892
United States

Therese White, RN
Phone: 301-402-5886
Email: whiteth@mail.nih.gov

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: February 03, 2023

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