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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT03406156

Recruitment Status : Recruiting

First Posted : January 23, 2018

Last Update Posted : July 29, 2019

See Contacts and Locations

Sponsor:

Information provided by (Responsible Party):

AbbVie

Study Description

Brief Summary:

A study in previously untreated Chronic Lymphocytic Leukemia to evaluate alternate administration strategies for induction therapy (debulking) with obinutuzumab or obinutuzumab/bendamustine prior to combination therapy with obinutuzumab and venetoclax.

Condition or disease	Intervention/treatment	Phase
Chronic Lymphocytic Leukemia (CLL) Small Lymphocytic Lymphoma (SLL)	Drug: Obinutuzumab Drug: Bendamustine Drug: Venetoclax	Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	120 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 3b 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
Actual Study Start Date :	August 10, 2018
Estimated Primary Completion Date :	April 3, 2022
Estimated Study Completion Date :	July 16, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Bendamustine hydrochloride Bendamustine Obinutuzumab Venetoclax

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Chromosome 17p Deletion

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Obinutuzumab +/- bendamustine then obinutuzumab + venetoclax Debulking Period: Obinutuzumab with or without bendamustine (bendamustine administered in participants with high tumor load as described in the protocol) during the debulking period (up to 6 cycles). Treatment Period: Venetoclax + obinutuzumab regimen initiated when participant achieves low tumor burden during debulking period, or if the participant has not achieved low tumor burden status after 6 cycles of debulking, the participant may proceed to venetoclax per the discretion of the treating provider after discussion with the study physician. During this regimen period, participants to receive obinutuzumab in combination with venetoclax for 5 months then venetoclax therapy alone to continue for a total duration of 52 weeks.	Drug: Obinutuzumab intravenous Other Name: Gazyva Drug: Bendamustine intravenous Other Name: Bendeka Drug: Venetoclax tablet Other Names: Venclexta ABT-199 GDC-0199

Arm

Intervention/treatment

Experimental: Obinutuzumab +/- bendamustine then obinutuzumab + venetoclax

Debulking Period: Obinutuzumab with or without bendamustine (bendamustine administered in participants with high tumor load as described in the protocol) during the debulking period (up to 6 cycles).

Treatment Period: Venetoclax + obinutuzumab regimen initiated when participant achieves low tumor burden during debulking period, or if the participant has not achieved low tumor burden status after 6 cycles of debulking, the participant may proceed to venetoclax per the discretion of the treating provider after discussion with the study physician. During this regimen period, participants to receive obinutuzumab in combination with venetoclax for 5 months then venetoclax therapy alone to continue for a total duration of 52 weeks.

Drug: Obinutuzumab

intravenous

Other Name: Gazyva

Drug: Bendamustine

intravenous

Other Name: Bendeka

Drug: Venetoclax

tablet

Other Names:

Venclexta
ABT-199
GDC-0199

Outcome Measures

Primary Outcome Measures :

Percent of Participants Achieving Low Tumor Burden Status with induction of Obinutuzumab or Obinutuzumab plus Bendamustine (Debulking Period) [ Time Frame: Up to approximately 24 weeks after initial dose of study drug ]
Low tumor burden is defined by peripheral lymphocyte counts of < 25,000 and all lymph nodes < 5 cm per CT scans.
Complete Remission Rate (CR) and Complete Remission with Incomplete Marrow Recovery (CRi) [ Time Frame: Up to approximately 65 weeks after initial dose of venetoclax ]
Defined as the proportion of subjects who achieved CR or CRi (per the 2008 Modified International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-sponsored Working Group [IWCLL NCI-WG] criteria).

Secondary Outcome Measures :

Overall Response Rate (ORR) [ Time Frame: Up to approximately 3.5 years after initial dose of study drug ]
ORR is defined as the proportion of participants with an overall response (CR, CRi, nodular partial remission [nPR] plus partial remission [PR]) per the 2008 Modified IWCLL NCI-WG criteria.
Duration of Response (DoR) [ Time Frame: Up to approximately 3.5 years after initial dose of study drug ]
DOR defined as the number of days from the date of first response (CR, CRi, nPR, or PR) (per the 2008 Modified IWCLL NCI-WG criteria) to the date of disease progression or death. All disease progression will be included regardless whether the event occurred during or after the participant was taking any study drug (either venetoclax, obinutuzumab, or bendamustine).
Progression-Free Survival (PFS) [ Time Frame: Up to approximately 3.5 years after initial dose of study drug ]
PFS is defined as the number of days from the date of first dose of any study drug (either venetoclax, obinutuzumab, or bendamustine) to the date of disease progression or death, whichever occurs first. All disease progression will be included regardless whether the event occurred during or after the participant was taking any study drug.
Time to Progression (TTP) [ Time Frame: Up to approximately 3.5 years after initial dose of study drug ]
TPP is defined as the number of days from the date of first dose of any study drug (either venetoclax, obinutuzumab, or bendamustine) to date of disease progression. All disease progression will be included regardless whether the event occurred during or after the participant was taking any study drug.
Overall Survival (OS) [ Time Frame: Up to approximately 3.5 years after initial dose of study drug ]
OS is defined as number of days from the date of first dose of any study drug (either venetoclax, obinutuzumab, or bendamustine) to the date of death.
Minimal Residual Disease (MRD) Negativity Rate [ Time Frame: Up to approximately 3.5 years after initial dose of study drug ]
MRD negativity defined as less than one CLL cell per 10,000 leukocytes (or below 10^-4). Rate of MRD status will be defined as the proportion of participants who have MRD negativity status.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 99 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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 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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03406156

Contacts

Layout table for location contacts

Contact: ABBVIE CALL CENTER	847.283.8955	abbvieclinicaltrials@abbvie.com

Locations

Layout table for location information

United States, Arizona
Arizona Oncology Associates, PC-HOPE /ID# 202335	Recruiting
Tucson, Arizona, United States, 85711-2701
United States, Colorado
Rocky Mountain Cancer Centers - Denver Midtown /ID# 202328	Recruiting
Denver, Colorado, United States, 80218
United States, Missouri
MidAmerica Division, Inc. /ID# 201099	Recruiting
Kansas City, Missouri, United States, 64132
United States, Ohio
Oncology Hematology Care, Inc - Kenwood /ID# 202397	Recruiting
Cincinnati, Ohio, United States, 45236-2725
United States, Oregon
Willamette Valley Cancer Institute /ID# 201201	Recruiting
Eugene, Oregon, United States, 97401-6043
United States, South Carolina
Greenville Health System - Int'l Dr /ID# 202329	Recruiting
Greenville, South Carolina, United States, 29615
United States, Tennessee
Tennessee Oncology - Chattanooga /ID# 202840	Recruiting
Chattanooga, Tennessee, United States, 37404-1108
Tennessee Oncology-Nashville Centennial /ID# 201098	Recruiting
Nashville, Tennessee, United States, 37203-1632
United States, Texas
Texas Oncology - Austin Midtown /ID# 201199	Recruiting
Austin, Texas, United States, 78705
Texas Oncology - Beaumont /ID# 202359	Recruiting
Beaumont, Texas, United States, 77701-4691
Texas Oncology - Dallas /ID# 201196	Recruiting
Dallas, Texas, United States, 75230
Texas Oncology - McAllen /ID# 202331	Recruiting
McAllen, Texas, United States, 78503
Texas Oncology - San Antonio Medical Center /ID# 202332	Recruiting
San Antonio, Texas, United States, 78240-5251
Texas Oncology - Tyler /ID# 201211	Recruiting
Tyler, Texas, United States, 75702
United States, Washington
Northwest Cancer Specialists, P.C. /ID# 201198	Recruiting
Vancouver, Washington, United States, 98684

Sponsors and Collaborators

AbbVie

Investigators

Layout table for investigator information

Study Director:	AbbVie Inc.	AbbVie

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Layout table for additonal information

Responsible Party:	AbbVie
ClinicalTrials.gov Identifier:	NCT03406156 History of Changes
Other Study ID Numbers:	M16-788
First Posted:	January 23, 2018 Key Record Dates
Last Update Posted:	July 29, 2019
Last Verified:	July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials:	Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) Analytic Code
Time Frame:	Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
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 (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL:	https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No
Product Manufactured in and Exported from the U.S.:	No

Keywords provided by AbbVie:


Cancer Chronic Lymphocytic Leukemia 17p Deletion debulking obinutuzumab	bendamustine tumor lysis syndrome venetoclax Small Lymphocytic Lymphoma

Additional relevant MeSH terms:

Layout table for MeSH terms

Leukemia Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases	Leukemia, B-Cell Bendamustine Hydrochloride Venetoclax Obinutuzumab Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antineoplastic Agents, Immunological

To Top