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

Phase 1

Terminated

• Conditions: Non-Hodgkins Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; B-cell Lymphomas; Waldenstrom's Macroglobulinemia; Marginal Zone Lymphoma; Mantle Cell Lymphoma
• Interventions: Drug: Ublituximab; Drug: Lenalidomide

• Registration Number: NCT01744912
• Lead Sponsor: TG Therapeutics, Inc.

Brief Summary

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

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.

Study Timeline

• Study Start: 2012-11-21
• Study First Submitted: 2012-12-05
• Study First Submitted QC: 2012-12-05
• Study First Posted: 2012-12-07
• Primary Completion: 2014-02-07
• Study Completion: 2014-02-07
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-05
• Last Update Posted: 2022-05-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ublituximab + Lenalidomide	Ublituximab	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.
Ublituximab + Lenalidomide	Lenalidomide	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.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose acceptable for participants	4 weeks	The Maximum Tolerated Dose will be determined by a Data Safety Monitoring Board

Secondary Outcome Measures

Name	Time	Method
Efficacy	After 8 weeks and then every 12 weeks	Efficacy will include overall response rate and duration of response

Trial Locations

Locations (1)

TG Therapeutics Investigational Trial Site; 🇺🇸 Bethesda, Maryland, United States