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

NCT03406156 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: M16-788
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

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

Keywords

Cancer; Chronic Lymphocytic Leukemia; 17p Deletion; Debulking; Obinutuzumab; Bendamustine; Tumor lysis syndrome; Venetoclax; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Achieving Low Tumor Burden Status With Induction of Obinutuzumab or Obinutuzumab Plus Bendamustine (Debulking Period)

  Low tumor burden is defined as absolute lymphocyte count (ALC) \< 25 × 10\^9 /L and all lymph nodes \< 5 cm per computed tomography (CT) scans.

  From Baseline to the end of Cycles 2, 4, and 6, up to approximately 24 weeks after initial dose of study drug

• Complete Remission Rate

  Complete remission rate is defined as the percentage of participants achieving complete remission (CR) or complete remission with incomplete marrow recovery (CRi) as their best response based on 2008 Modified International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (IWCLL NCI-WG) criteria. CR required all of the following: * Peripheral blood lymphocytes \<4000/μL * Absence of lymphadenopathy by physical examination and computed tomography scan * No hepatomegaly or splenomegaly * Absence of disease or constitutional symptoms (unexplained fevers \>38°C, drenching night sweats, ≥10% weight loss in last 6 months) * Blood counts above the following: * Neutrophils \>1500/μL * Platelets \>100,000/μL * Hemoglobin \>11.0 g/dL * Bone marrow at least normocellular for age, \<30% lymphocytes CRi was defined as participants with CR who had persistent cytopenia unrelated to CLL but related to drug toxicity.

  From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021); overall median time on follow-up was up to 787 days

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021); overall median time on follow-up was up to 787 days

• Duration of Response (DoR)

  From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021); overall median time on follow-up was up to 787 days

• Progression-Free Survival (PFS)

  From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021); overall median time on follow-up was up to 787 days

• Time to Progression (TTP)

  From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021); overall median time on follow-up was up to 787 days

• Overall Survival (OS)

  From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021); overall median time on follow-up was up to 787 days

Study Arms (2)

Obinutuzumab

EXPERIMENTAL

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.

Drug: Obinutuzumab; Drug: Venetoclax

Obinutuzumab/bendamustine

EXPERIMENTAL

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.

Drug: Obinutuzumab; Drug: Bendamustine; Drug: Venetoclax

Interventions

Obinutuzumab DRUG

Administered via intravenous infusion

Also known as: Gazyva

Obinutuzumab; Obinutuzumab/bendamustine

Bendamustine DRUG

Administered via intravenous infusion

Also known as: Bendeka

Obinutuzumab/bendamustine

Venetoclax 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.

Also known as: Venclexta, ABT-199, GDC-0199

Obinutuzumab; Obinutuzumab/bendamustine

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie: lead

Study Sites (15)

Arizona Oncology Associates, PC-HOPE /ID# 202335

Tempe, Arizona, 85284-1812, United States

Location

Rocky Mountain Cancer Centers - Denver Midtown /ID# 202328

Denver, Colorado, 80218, United States

Location

MidAmerica Division, Inc. /ID# 201099

Kansas City, Missouri, 64132, United States

Location

Oncology Hematology Care, Inc. /ID# 202397

Cincinnati, Ohio, 45236-2725, United States

Location

Willamette Valley Cancer Institute and Research Center /ID# 201201

Eugene, Oregon, 97401-6043, United States

Location

Prisma Health Cancer Inst - Eastside /ID# 202329

Greenville, South Carolina, 29615, United States

Location

Tennessee Oncology - Chattanooga /ID# 202840

Chattanooga, Tennessee, 37404-1108, United States

Location

Tennessee Oncology-Nashville Centennial /ID# 201098

Nashville, Tennessee, 37203-1632, United States

Location

Texas Oncology - Austin Midtown /ID# 201199

Austin, Texas, 78705, United States

Location

Texas Oncology - Beaumont /ID# 202359

Beaumont, Texas, 77701-4691, United States

Location

Texas Oncology - Medical City Dallas /ID# 201196

Dallas, Texas, 75230, United States

Location

Texas Oncology - McAllen /ID# 202331

McAllen, Texas, 78503, United States

Location

Texas Oncology - San Antonio Medical Center /ID# 202332

San Antonio, Texas, 78240-5251, United States

Location

Texas Oncology - Northeast Texas /ID# 201211

Tyler, Texas, 75702, United States

Location

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

Vancouver, Washington, 98684, United States

Location

Related Publications (6)

• 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

  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

  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

  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

  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

  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

  RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms; Chromosome 17 deletion; Tumor Lysis Syndrome

Interventions

obinutuzumab; Bendamustine Hydrochloride; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: January 16, 2018
• First Posted: January 23, 2018
• Study Start: August 10, 2018
• Primary Completion: October 12, 2021
• Study Completion: July 12, 2023
• Last Updated: August 6, 2024
• Results First Posted: November 3, 2022

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/

Locations

US (15)