Study to Assess the Efficacy and Safety of Ublituximab in Combination With Umbralisib and Venetoclax Compared to Ublituximab in Combination With Umbralisib in Subjects With CLL (ULTRA-V)

TG Therapeutics

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

Treatments: Drug: Umbralisib; Drug: Venetoclax; Drug: Ublituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03801525

U2-VEN-207

Details and patient eligibility

About

ULTRA-V: Study to Assess the Efficacy and Safety of Ublituximab in Combination with Umbralisib and Venetoclax (U2-V) Compared to Ublituximab and Umbralisib (U2) in Subjects with Chronic Lymphocytic Leukemia (CLL)

Full description

This is an open-label, multicenter, Phase 2/3 study to evaluate the efficacy and safety of the combination of ublituximab + umbralisib + venetoclax (U2-V) compared to the combination of ublituximab + umbralisib (U2) in participants with either treatment naïve or previously treated CLL/ small lymphocytic lymphoma (SLL).

Enrollment: 277 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) that warrants treatment
• Adequate organ system function as specified in the protocol
• Ability to follow protocol procedures.

Exclusion criteria

• Subjects receiving cancer therapy or any investigational drug within 21 days of Cycle 1, Day 1
• Prior exposure to any PI3K inhibitor or venetoclax
• Autologous hematologic stem cell transplant within 6 months of study entry. Prior allogeneic hematologic stem cell transplant is excluded
• Active Hepatitis B or Hepatitis C.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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277 participants in 3 patient groups

Phase 2: Ublituximab + Umbralisib + Venetoclax (U2-V)

Experimental group

Description:

Participants were administered ublituximab, 150 milligrams (mg), intravenous (IV) infusion on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1, followed by 900 mg on Day 1 of Cycles 2-6; umbralisib, 800 mg, oral tablet, once daily (QD) through Cycles 1-24; venetoclax, oral tablet, QD, 20 mg on Days 1-7, 50 mg on Days 8-14, 100 mg on Days 15-21, 200 mg on Days 22-28 of Cycle 4, followed by 400 mg on Days 1-28 of Cycles 5-24. MRD positive participants were administered umbralisib, 800 mg, oral tablet, QD, on Days 1-28 from Cycle 25 onwards (1 Cycle = 28 days), until disease progression, unacceptable toxicity, or withdrawal from the study.

Treatment:

Drug: Umbralisib

Drug: Ublituximab

Drug: Venetoclax

Phase 3: Ublituximab + Umbralisib + Venetoclax (U2-V)

Experimental group

Description:

Participants were administered ublituximab, 150 mg, IV infusion on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1, followed by 900 mg on Day 1 of Cycles 2-6, 9,12, and 15; umbralisib, 800 mg, oral tablet, QD through Cycles 1-15; venetoclax, oral tablet, QD, 20 mg on Days 1-7, 50 mg on Days 8-14, 100 mg on Days 15-21, 200 mg on Days 22-28 of Cycle 4, followed by 400 mg on Days 1-28 of Cycles 5-15 (1 Cycle = 28 days).

Treatment:

Drug: Umbralisib

Drug: Ublituximab

Drug: Venetoclax

Phase 3: Ublituximab + Umbralisib (U2)

Experimental group

Description:

Participants were administered ublituximab, 150 mg, IV infusion on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1, followed by 900 mg on Day 1 of Cycles 2-6, then every three cycles along with umbralisib, 800 mg, oral tablet, QD (1 Cycle = 28 days) from Cycle 1 until disease progression, unacceptable toxicity, or withdrawal from the study.

Treatment:

Drug: Umbralisib

Drug: Ublituximab