A Study in Previously Untreated Chronic Lymphocytic Leukemia (CLL) Subjects, Excluding Those With the 17p Deletion, to Evaluate Debulking Regimens Prior to Initiating Venetoclax Combination Therapy

AbbVie

Status and phase: Completed; Phase 3

Conditions: Small Lymphocytic Lymphoma (SLL); Chronic Lymphocytic Leukemia (CLL)

Treatments: Drug: Venetoclax; Drug: Bendamustine; Drug: Obinutuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03406156

M16-788

Details and patient eligibility

About

This is a multi-cohort, open-label study in previously untreated participants with chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), excluding those with the 17p deletion, to evaluate a debulking strategy that would enable all participants to receive subsequent venetoclax as outpatients, with lower risk of tumor lysis syndrome.

Full description

Safety and efficacy data through 13 October 2021 are included in the interim analysis, which was conducted after all participants completed the post-treatment Week 65 visit or discontinued from the study.

Enrollment: 120 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adequate hematology, kidney and liver function as described in the protocol
• Diagnosis of previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) according to 2008 Modified International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-sponsored Working Group (IWCLL NCI-WG) criteria
• Eastern Cooperative Oncology Group (ECOG) performance score of 0 - 1
• CLL/SLL requires treatment according to the IWCLL criteria
• Medium tumor burden (any lymph node [LN] 5 to < 10 cm OR absolute lymphocyte count [ALC] ≥ 25 × 10^9/L) OR High tumor burden (any LN ≥ 10 cm OR ALC ≥ 25 × 10^9/L and LN ≥ 5 cm)

Exclusion criteria

• Presence of 17p deletion at Screening
• Richter's syndrome (transformation of CLL/SLL to aggressive non-Hodgkin's lymphoma or Hodgkin's lymphoma)
• Prolymphocytic leukemia

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

120 participants in 2 patient groups

Obinutuzumab

Experimental group

Description:

Obinutuzumab (100 mg on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, and 1000 mg on Days 8 and 15 of Cycle 1 and Day 1 of Cycle 2; for Cycles 3 - 6 (1000 mg on Day 1) only as needed for participants to achieve low tumor burden) was administered via intravenous infusion during the debulking regimen. After debulking, obinutuzumab (1000 mg) was administered via intravenous infusion on Day 1 of one 5-week and four 4-week cycles during the obinutuzumab/venetoclax combination part of the regimen. Venetoclax was administered according to a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg.

Treatment:

Drug: Obinutuzumab

Drug: Venetoclax

Obinutuzumab/bendamustine

Experimental group

Description:

Obinutuzumab (100 mg on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, and 1000 mg on Days 8 and 15 of Cycle 1 and Day 1 of Cycle 2; for Cycles 3 - 6 (1000 mg on Day 1) only as needed for participants to achieve low tumor burden) was administered via intravenous infusion during the debulking regimen. Bendamustine (90 mg/m\^2 ) was to be administered to those with nodes or nodal mass \> 10 cm, or with del(11q) and \> 5 cm nodes, or at the discretion of the investigator as above, via intravenous infusion over 10 minutes on Days 1 and 2 (or Days 2 and 3 at the discretion of the investigator during Cycle 1) of each 28-day cycle for up to 6 cycles during the debulking regimen. After debulking, obinutuzumab (1000 mg) was administered via intravenous infusion on Day 1 of one 5-week and four 4-week cycles during the obinutuzumab/venetoclax combination part of the regimen. Venetoclax was administered according to a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg.

Treatment:

Drug: Obinutuzumab

Drug: Bendamustine

Drug: Venetoclax