A Trial of the Safety of Escalating Doses of PRO131921 in Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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This is an open-label, multicenter, Phase I/II study of the safety of escalating doses of single-agent PRO131921 in patients with relapsed or refractory CD20-positive indolent NHL. The trial will enroll in two phases: a Phase I dose-escalation portion for patients with indolent NHL and a Phase II portion with enrollment of additional patients with follicular NHL into two expanded treatment cohorts in order to expand the safety database and collect preliminary anti-lymphoma activity data.

Official Title
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An Open-Label, Multicenter, Phase I/II Trial of the Safety of Escalating Doses of PRO131921 in Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma Who Have Been Treated With a Prior Rituximab-Containing Regimen

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: PRO131921


Participation Criteria
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Eligibility Criteria
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Signed informed consent Ability and willingness to comply with the requirements of the study protocol Age ≥ 18 years Documented history of histologically confirmed CD20-positive follicular NHL (Phases I and II); for Phase I, other CD20-positive indolent lymphomas (marginal zone lymphoma and small lymphocytic lymphoma) are also included. Patients with a history of a CD20-positive NHL of mixed (indolent/aggressive) histology may also be included in Phase I if the most recent relapse biopsy shows only indolent NHL Indolent lymphoma (Phase I) or follicular lymphoma (Phase II) that either has relapsed after a documented history of response (CR, CRu, or PR) of ≥6 months to a rituximab-containing regimen or was refractory to a previous rituximab-containing regimen Bi-dimensionally measurable disease, with at least one lesion >1.5 cm in its largest dimension Absolute B-cell count ≥LLN at screening (Phase I only) ECOG performance status of 0, 1, or 2 For patients of reproductive potential (males and females), use of a reliable means of contraception during the study and for 1 year following the last dose of study treatment For females of childbearing potential, a negative serum pregnancy test within 14 days prior to enrollment Exclusion Criteria: Prior use of anti-CD20 monoclonal antibody therapy (other than rituximab or radioimmunotherapy) Prior use of any non-CD20-targeted monoclonal antibody therapy within 6 months of enrollment Current or recent lymphoma treatment History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies Evidence of significant uncontrolled concomitant diseases, such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders Evidence of myelodysplasia or myelodysplastic changes on bone marrow examination Untreated or persistent/recurrent malignancy (other than lymphoma) Known active bacterial, viral, fungal, mycobacterial, or other infection A major episode of infection requiring hospitalization or treatment with IV antimicrobials within 4 weeks of screening or oral antimicrobials within 2 weeks of screening History of recurrent significant infection or bacterial infections Positive hepatitis B or C serology Positive human immunodeficiency virus (HIV) serology Pregnancy or lactation Central nervous system lymphoma Recent major surgery within 4 weeks of screening, other than diagnostic surgery

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: PRO131921<br>* Escalating doses by IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities and adverse events |  | Length of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters; CD19-positive B-cell counts |  | Length of study | 
| Overall response; and progression-free survival (Ph. 2 only) |  | Length of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NHL, Indolent, Follicular