Ublituximab in Combination With Lenalidomide in Patients With B-Cell Lymphoid Malignancies

Study Overview
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Brief Summary
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The purpose of this study is to determine whether ublituximab in combination with lenalidomide (Revlimid®) is safe and effective in patients with B-Cell Lymphoid Malignancies who have relapsed or are refractory after CD20 directed antibody therapy.

Detailed Description
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The study was intended to be a Phase 1/2 study, however, the study was terminated early and the phase 2 portion was never initiated. A limited number of participants were enrolled in Phase 1 and no maximum tolerated dose (MTD) or Phase 2 dose was identified for the combination of ublituximab and lenalidomide. Thus, Phase 2 data and results are not available to be reported.

Official Title
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A Phase I/II Study of Ublituximab in Combination With Lenalidomide (Revlimid®) in Patients With B-Cell Lymphoid Malignancies Who Have Relapsed or Are Refractory After CD20 Directed Antibody Therapy

Conditions
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Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, B-cell Lymphomas, Marginal Zone Lymphoma, Mantle Cell Lymphoma, Waldenstrom's Macroglobulinemia

Intervention / Treatment
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* Drug: Ublituximab
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory B-cell non-Hodgkins Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Participants must have received at least one prior line of therapy with an anti-CD20 antibody (i.e. rituximab, ofatumumab, etc.) or an anti-CD20 antibody containing regimen Measurable or evaluable Disease Eastern Cooperative Oncology Group performance status 0, 1 or 2 Participants ineligible for high dose or combination chemotherapy + stem cell transplant No active or chronic infection of Hepatitis B or C and no history of HIV based on negative serology All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist® Exclusion Criteria: Prior chemotherapy, investigational therapy or radiotherapy within 3 weeks of study entry Prior autologous or allogeneic stem cell transplantation within 6 months of study entry History of severe hypersensitivity or anaphylaxis to prior murine or mouse/human chimeric antibodies, or to any component of ublituximab, or with prior lenalidomide or thalidomide Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements History of deep vein thrombosis (DVT) or pulmonary embolus (PE) in the six months prior to Day 1 of Cycle 1 Pregnant women

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: Ublituximab + Lenalidomide<br>4 cohorts, with 3 - 6 patients per cohort, as follows: Cohort 1: Ublituximab 450 mg + Lenalidomide 10 mg Cohort 2: Ublituximab 450 mg + Lenalidomide 15 mg Cohort 3: Ublituximab 600 mg + Lenalidomide 10 mg (escalation to 15 mg permitted after cycle 1) Cohort 4: Ublituximab 900 mg + Lenalidomide 10 mg (escalation to 15 mg permitted after cycle 1) Ublituximab is an IV infusion on days 1, 8, and 15 of cycles 1 & 2 followed by a planned maintenance with a single infusion on day 1 of cycles 3 thru 6. Lenalidomide is taken orally on days 9 - 28 of cycle 1 followed by daily administration on Days 1 - 28 for cycles 2 thru 6. Non-hodgkins lymphoma patients may have up to a 7 day rest period (Days 21-28) in any cycle. | Drug: Ublituximab<br>* Ublituximab is a novel monoclonal antibody targeting CD20<br>* Other names: TG-1101;Drug: Lenalidomide<br>* Lenalidomide has both immunomodulatory and anti-angiogenic properties which could confer antitumor and antimetastatic effects<br>* Other names: Revlimid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose acceptable for participants | The Maximum Tolerated Dose will be determined by a Data Safety Monitoring Board | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Efficacy will include overall response rate and duration of response | After 8 weeks and then every 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lenalidomide, Lymphoma, monoclonal antibody, immunomodulatory agent, ublituximab