Phase I Trial of Anti-CD74 (hLL1) Antibody Therapy in B Cell Malignancies

Study Overview
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Brief Summary
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Previous experience with antibody therapy in both NHL and CLL warrants further exploration of new antibody treatments for these diseases. Immunomedics has developed hLL1 (previously designated EPB-1), which is a CDR-grafted, fully humanized monoclonal antibody specifically targeting CD74.38 The human IgG1 backbone for hLL1 is the same as hLL2 (epratuzumab), a monoclonal antibody whose safety has been demonstrated in clinical trials of patients with B-cell malignancies and autoimmune disorders. This is a Phase I, open-label, study conducted in patients with recurrent non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL) who have progressed after at least one prior standard treatment. All patients will receive hLL1 administered intravenously once daily Monday through Friday of each of 2 consecutive weeks (10 total doses.) Patients will be assigned to a cohort for hLL1 treatment dose assignment (escalating doses of hLL1 per statistical plan) in order to determine the maximum tolerated dose (MTD) for this administration schedule.

Official Title
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Phase I Trial of Anti-CD74 (hLL1) Antibody Therapy in B Cell Malignancies

Conditions
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Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: hLL1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of recurrent B cell non-Hodgkin's lymphoma or diagnosis of recurrent chronic lymphocytic leukemia Patient has received at least one prior treatment with standard chemotherapy and at least one prior treatment with rituximab (negative HAHA test required if received prior humanized antibody treatment) Patient has not received anti-cancer therapy within 28 days of treatment unless disease progression has been demonstrated and toxicities from prior therapy have resolved Available tumor tissue (lymph node/mass, blood or bone marrow) for correlative analyses (paraffin or frozen, recent or archived) Measurable disease as defined by a tumor mass > 1.5 cm in one dimension or WBC > 5,000 (CLL patients) Age > 18 years Patient has KPS > 50% Absolute granulocyte count > 1000 cells/mm3 Platelet count > 50,000 cells/mm3 Creatinine < 2.0 x ULN Total bilirubin < 2.0 x ULN Patient agrees to use birth control if of reproductive potential Patient has signed IRB-approved informed consent Exclusion Criteria: Known central nervous system (CNS) involvement by lymphoma Known HIV disease Patient is pregnant or nursing Patient is receiving other investigational drugs Known serum human anti-human antibodies (HAHA) Estimated life expectancy of < 3 months

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: Study Treatment<br>This study is a single arm study | Drug: hLL1<br>* hLL1 administered intravenously once daily Monday through Friday for 2 consecutive weeks (10 total doses) at one of 4 planned dose levels: 1.5, 4, 6 or 8 mg/kg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the toxicity profile and maximum tolerated dose (MTD) of hLL1 when administered to patients with recurrent non-Hodgkin's lymphoma and chronic lymphocytic leukemia |  | duration of study |