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

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.

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: hLL1

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Treatment; This study is a single arm study	Drug: hLL1; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Gilead Sciences

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): October 7, 2015

Study Registration Dates

• First Submitted: July 19, 2007
• First Submitted That Met QC Criteria: July 19, 2007
• First Posted (Estimate): July 20, 2007

Study Record Updates

• Last Update Posted (Actual): May 29, 2018
• Last Update Submitted That Met QC Criteria: May 25, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell
• Other Study ID Numbers: 0608008669

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No