Safety Study of Different Doses of hA20 (Veltuzumab) in CD20+ Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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This study is being done to assess the safety and tolerance of different doses of humanized hA20 in patients with NHL.

Official Title
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A Phase I Study of Immunotherapy With hA20 Administered Once Weekly for 4 Consecutive Weeks in Patients With CD20+ Non- Hodgkin's Lymphoma

Conditions
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Non-Hodgkin's Lymphoma, Lymphoma, Diffuse, Lymphoma, Diffuse, Mixed Lymphocytic-Histiocytic

Intervention / Treatment
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* Drug: veltuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, >18 years old Histological diagnosis of CD20+ B-cell NHL (all grades) by WHO lymphoma criteria Failed at least one prior standard chemotherapy regimen for NHL Failed rituximab treatment for relapsed NHL Measurable NHL disease by CT, with at least one lesion >1.5 cm in one dimension Adequate performance status (>70 Karnofsky scale, 0-1 ECOG) with an estimated life expectancy of at least 6 months Adequate hematologic status, without ongoing transfusional support (hemoglobin ≥ 10 g/dL, ANC ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L) Adequate renal and hepatic function, defined as: creatinine ≤ 1.5 x Institution Upper Limit of Normal (IULN), bilirubin ≤ 1.5 x IULN, AST and ALT ≤ 2.5 x IULN Otherwise, <Grade 1 toxicity at study entry by NCI CTC version 2.0, including recovery from all acute toxicities incurred as a result of previous surgery, radiotherapy or chemotherapy, whether investigational or conventional. At least 6 months beyond previous rituximab treatment, 12 weeks beyond autologous stem cell transplant, 4 weeks beyond chemotherapy, other experimental treatments, or any radiation therapy to the index lesion(s). Ability to provide signed, informed consent Exclusion Criteria: Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control while enrolled in the study until at least 12 weeks after the last weekly hA20 infusion. Rituximab resistant, defined as having progressed during or within 6 months of rituximab treatment. Excessive toxicity to rituximab (NCI CTC Grade 3 or 4) or known to be HACA positive Prior radioimmunotherapy, including Zevalin or Bexxar, Prior therapy with other human or humanized monoclonal antibodies, unless HAHA tested and negative Primary CNS lymphoma, HIV lymphoma or transformed lymphoma, or presence of symptomatic CNS metastases or carcinomatous meningitis. Bulky disease by CT, defined as any single mass >10 cm in its greatest diameter Pleural effusion with positive cytology for lymphoma Known to be HIV positive, or hepatitis B or C positive Known autoimmune disease or presence of autoimmune phenomena. Evidence of infection or requiring antibiotics within 5 days. Corticosteroid use within 2 weeks Prior malignancy with less than a 5-year disease-free interval, excluding nonmelanoma skin cancers and carcinoma in situ of the cervix. Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of studyprocedures and follow-up examinations

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: veltuzumab|once weekly intravenous dosing for 4 weeks|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of hA20 with this administration schedule and dosing |  | first 12 weeks, then over 2 years | 
| tolerance of hA20 with this administration schedule and dosing |  | first 12 weeks | 
| immunogenicity of hA20 with this administration schedule and dosing |  | first 12 weeks, as needed over 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics of hA20 |  | first 12 weeks, then up to 2 years | 
| pharmacokinetics hA20 |  | first 12 weeks, then up to 2 years | 
| assess efficacy |  | 4 and 12 weeks, then every 3 months for 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NHL, Non-Hodgkin's lymphoma, follicular lymphoma, B-cell lymphoma, diffuse large cell lymphoma, small lymphoctytic lymphoma, Mantle cell lymphoma, MALT, marginal zone lymphoma, High-Grade, Intermediate-Grade, Low-Grade, Mixed