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

• ClinicalTrials.gov Identifier: NCT03406156
• Recruitment Status: Active, not recruiting
• First Posted: January 23, 2018
• Last Update Posted: March 6, 2020
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Study Description

Brief Summary:

A study in previously untreated Chronic Lymphocytic Leukemia participants 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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 121 participants
• Allocation: N/A
• 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: November 30, 2021
• Estimated Study Completion Date: September 11, 2023

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 up to 53 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 :

1. 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.
2. 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 :

1. 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.
2. 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).
3. 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.
4. 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.
5. 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.
6. Undetectable Minimal Residual Disease (UMRD) Rate [ Time Frame: Up to approximately 3.5 years after initial dose of study drug ]
   UMRD defined as less than one CLL cell per 10,000 leukocytes (or below 10^-4). Rate of UMRD status will be defined as the percentage of participants who have UMRD.

Eligibility Criteria

• 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

Locations

United States, Arizona

Arizona Oncology Associates, PC-HOPE /ID# 202335

Tucson, Arizona, United States, 85711-2701

United States, Colorado

Rocky Mountain Cancer Centers - Denver Midtown /ID# 202328

Denver, Colorado, United States, 80218

United States, Missouri

MidAmerica Division, Inc. /ID# 201099

Kansas City, Missouri, United States, 64132

United States, Ohio

Oncology Hematology Care, Inc - Kenwood /ID# 202397

Cincinnati, Ohio, United States, 45236-2725

United States, Oregon

Willamette Valley Cancer Institute /ID# 201201

Eugene, Oregon, United States, 97401-6043

United States, South Carolina

Greenville Health System - Int'l Dr /ID# 202329

Greenville, South Carolina, United States, 29615

United States, Tennessee

Tennessee Oncology - Chattanooga /ID# 202840

Chattanooga, Tennessee, United States, 37404-1108

Tennessee Oncology-Nashville Centennial /ID# 201098

Nashville, Tennessee, United States, 37203-1632

United States, Texas

Texas Oncology - Austin Midtown /ID# 201199

Austin, Texas, United States, 78705

Texas Oncology - Beaumont /ID# 202359

Beaumont, Texas, United States, 77701-4691

Texas Oncology - Medical City Dallas /ID# 201196

Dallas, Texas, United States, 75230

Texas Oncology - McAllen /ID# 202331

McAllen, Texas, United States, 78503

Texas Oncology - San Antonio Medical Center /ID# 202332

San Antonio, Texas, United States, 78240-5251

Texas Oncology - Tyler /ID# 201211

Tyler, Texas, United States, 75702

United States, Washington

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

Vancouver, Washington, United States, 98684

Sponsors and Collaborators

AbbVie

Investigators

• Study Director: AbbVie Inc.; AbbVie

More Information

Additional Information:

Related Info 

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT03406156
• Other Study ID Numbers: M16-788
• First Posted: January 23, 2018
• Last Update Posted: March 6, 2020
• Last Verified: March 2020

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

• 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:

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