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

NCT ID: NCT03406156

Last Updated: 2024-08-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-10

Study Completion Date

2023-07-12

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Chronic Lymphocytic Leukemia (CLL) Small Lymphocytic Lymphoma (SLL)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Obinutuzumab

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.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

Administered via intravenous infusion

Venetoclax

Intervention Type DRUG

The venetoclax dose was administered according to a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg. Venetoclax was continued for a total duration of up to 53 weeks, including the 5-week ramp-up schedule. Participants were instructed to take venetoclax tablets with a meal and water at approximately the same time each day. Venetoclax tablets were to be swallowed whole and not chewed, crushed, or broken prior to swallowing.

Obinutuzumab/bendamustine

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.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

Administered via intravenous infusion

Bendamustine

Intervention Type DRUG

Administered via intravenous infusion

Venetoclax

Intervention Type DRUG

The venetoclax dose was administered according to a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg. Venetoclax was continued for a total duration of up to 53 weeks, including the 5-week ramp-up schedule. Participants were instructed to take venetoclax tablets with a meal and water at approximately the same time each day. Venetoclax tablets were to be swallowed whole and not chewed, crushed, or broken prior to swallowing.

Interventions

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Obinutuzumab

Administered via intravenous infusion

Intervention Type DRUG

Bendamustine

Administered via intravenous infusion

Intervention Type DRUG

Venetoclax

The venetoclax dose was administered according to a weekly ramp-up schedule over 5 weeks to the recommended daily dose of 400 mg. Venetoclax was continued for a total duration of up to 53 weeks, including the 5-week ramp-up schedule. Participants were instructed to take venetoclax tablets with a meal and water at approximately the same time each day. Venetoclax tablets were to be swallowed whole and not chewed, crushed, or broken prior to swallowing.

Intervention Type DRUG

Other Intervention Names

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Gazyva Bendeka Venclexta ABT-199 GDC-0199

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

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Arizona Oncology Associates, PC-HOPE /ID# 202335

Tempe, Arizona, United States

Site Status

Rocky Mountain Cancer Centers - Denver Midtown /ID# 202328

Denver, Colorado, United States

Site Status

MidAmerica Division, Inc. /ID# 201099

Kansas City, Missouri, United States

Site Status

Oncology Hematology Care, Inc. /ID# 202397

Cincinnati, Ohio, United States

Site Status

Willamette Valley Cancer Institute and Research Center /ID# 201201

Eugene, Oregon, United States

Site Status

Prisma Health Cancer Inst - Eastside /ID# 202329

Greenville, South Carolina, United States

Site Status

Tennessee Oncology - Chattanooga /ID# 202840

Chattanooga, Tennessee, United States

Site Status

Tennessee Oncology-Nashville Centennial /ID# 201098

Nashville, Tennessee, United States

Site Status

Texas Oncology - Austin Midtown /ID# 201199

Austin, Texas, United States

Site Status

Texas Oncology - Beaumont /ID# 202359

Beaumont, Texas, United States

Site Status

Texas Oncology - Medical City Dallas /ID# 201196

Dallas, Texas, United States

Site Status

Texas Oncology - McAllen /ID# 202331

McAllen, Texas, United States

Site Status

Texas Oncology - San Antonio Medical Center /ID# 202332

San Antonio, Texas, United States

Site Status

Texas Oncology - Northeast Texas /ID# 201211

Tyler, Texas, United States

Site Status

Northwest Cancer Specialists, P.C. /ID# 201198

Vancouver, Washington, United States

Site Status

Countries

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United States

References

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Flinn IW, Andorsky D, Melear J, Manda S, Anz B III, Kolibaba K, Yimer H, Burke JM, Fanning S, Courtright J, Islas-Ohlmayer M, Kambhampati S, Vizkelety T, Pesko J, Chyla B, Jiang D, Sharman JP. Debulking Before Initiation of Venetoclax Therapy in Untreated Patients with Chronic Lymphocytic Leukemia: Results from a Phase 3b Study. American Society of Hematology - 63rd Annual Meeting. 2021

Reference Type RESULT

Sharman J, Andorsky D, Melear J, Manda S, Anz B III, Kolibaba K, Yimer H, Burke J, Fanning S, Courtright J, Islas-Ohlmayer M, Kambhampati S, Jiang D, Pesko D, Vizkelety T, Sharmokh S, Nielsen J, Flinn I. Phase 3b study to evaluate debulking regimens prior to initiating venetoclax therapy in untreated patients with chronic lymphocytic leukemia. Florida Society of Clinical Oncology-2020 Fall Session

Reference Type RESULT

Flinn I, Andorsky D, Melear J, Manda S, Anz B III, Kolibaba K, Yimer H, Burke J, Fanning S, Courtright J, Islas-Ohlmayer M, Kambhampati S, Jiang D, Pesko D, Vizkelety T, Sharmokh S, Sharman J. Debulking Regimens Prior To Initiating Venetoclax Therapy in Untreated Patients with Chronic Lymphocytic Leukemia: Interim Results from a Phase 3b Study. American Society of Hematology - 62nd Annual Meeting. 2020

Reference Type RESULT

Sharman J, Andorsky D, Melear J, Manda S, Anz B III, Kolibaba K, Yimer H, Burke J, Fanning S, Courtright J, Islas-Ohlmayer M, Kambhampati S, Jiang D, Pesko J, Vizkelety T, Sharmokh S, Nielsen J, Flinn I. Phase 3b Study to Evaluate Debulking Regimens Prior to Initiating Venetoclax Therapy in Untreated Patients with Chronic Lymphocytic Leukemia. Society of Hematologic Oncology-8th Annual Meeting. 2020

Reference Type RESULT

Sharman J, Andorsky D. Melear J, Manda S, Anz B II, Kolibaba K, Yimer H, Burke J, Fanning S, Courtright J, Islas-Ohlmayer M, Kambhampati S, Jiang D, Pesko J, Vizkelety T, Sharmkokh S, Nielsen J, Flinn I. Phase 3b study to evaluate debulking regimens prior to initiating venetoclax therapy in untreated patients with chronic lymphocytic leukemia. European Hematology Association-25th Congress. 2020

Reference Type RESULT

Sharman J, Andorsky D, Melear J, Manda S, Anz B III, Kolibaba K, Yimer H, Burke J, Fanning S, Courtright J, Islas-Ohlmayer M, Kambhampati S, Al Masud A, Zimmerman T, Nielsen J, Vizkelety T, Jiang D, Flinn I. Debulking eliminates need for hospitalization prior to initiating frontline venetoclax therapy in previously untreated CLL patients: a phase 3b study. American Society of Hematology - 61st Annual Meeting. 2019

Reference Type RESULT

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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M16-788

Identifier Type: -

Identifier Source: org_study_id

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