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
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ClinicalTrials.gov Identifier: NCT03406156 |
Recruitment Status :
Active, not recruiting
First Posted : January 23, 2018
Results First Posted : November 3, 2022
Last Update Posted : November 3, 2022
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Condition or disease | Intervention/treatment | Phase |
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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 Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 120 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel 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 |
Actual Primary Completion Date : | October 12, 2021 |
Estimated Study Completion Date : | July 20, 2023 |

Arm | Intervention/treatment |
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Experimental: 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. |
Drug: Obinutuzumab
Administered via intravenous infusion
Other Name: Gazyva 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. 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.
Other Names:
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Experimental: 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. |
Drug: Obinutuzumab
Administered via intravenous infusion
Other Name: Gazyva Drug: Bendamustine Administered via intravenous infusion
Other Name: Bendeka 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. 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.
Other Names:
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- Percentage of Participants Achieving Low Tumor Burden Status With Induction of Obinutuzumab or Obinutuzumab Plus Bendamustine (Debulking Period) [ Time Frame: From Baseline to the end of Cycles 2, 4, and 6, up to approximately 24 weeks after initial dose of study drug ]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.
- Complete Response Rate [ Time Frame: 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 ]
Complete response 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 by physical examination
- Absence of disease or constitutional symptoms (unexplained fevers >38°C, drenching night sweats, ≥10% weight loss in last 6 months)
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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.
- Overall Response Rate (ORR) [ Time Frame: 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 ]ORR is defined as the percentage of participants who achieved a best response of complete remission (CR), complete remission with incomplete marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) based on the 2008 Modified IWCLL NCI-WG criteria at any time during the study as assessed by investigator up through the completion of the 65-week disease response assessment after the start of venetoclax. Participants who did not respond were considered non-responders.
- Duration of Response (DoR) [ Time Frame: 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 ]DoR is 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, whichever occurs first. All disease progression was to be included regardless whether the event occurred during or after the participant was taking any study drug (either venetoclax, obinutuzumab, or bendamustine). Duration of response was analyzed by Kaplan-Meier (K-M) methodology.
- Progression-Free Survival (PFS) [ Time Frame: 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 ]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 was to be included regardless whether the event occurred during or after the participant was taking any study drug. Progression-free survival was analyzed by Kaplan-Meier methodology.
- Time to Progression (TTP) [ Time Frame: 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 ]TTP 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 was to be included regardless of whether the event occurred during or after the participant was taking any study drug.The distribution of the time to progression was estimated using Kaplan-Meier methodology.
- Overall Survival (OS) [ Time Frame: 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 ]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. If a participant had not died, their data was censored at the date when they were last known to be alive prior to the cutoff date.The distribution of OS was estimated using Kaplan-Meier methodology.
- Undetectable Minimal Residual Disease (UMRD) Rate [ Time Frame: From first dose of study drug until the last participant completed Week 65 assessments (data cut-off date of 13 October 2021) ]The level of MRD was assessed in the peripheral blood of all participants at 5 months after last dose of obinutuzumab, and at 3 months after last dose of venetoclax/end of treatment (including early study termination) to determine the rate of UMRD. Undetectable Minimal Residual Disease is defined as less than one CLL cell per 10,000 leukocytes (< 10^-4 ).

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

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
United States, Arizona | |
Arizona Oncology Associates, PC-HOPE /ID# 202335 | |
Tempe, Arizona, United States, 85284-1812 | |
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. /ID# 202397 | |
Cincinnati, Ohio, United States, 45236-2725 | |
United States, Oregon | |
Willamette Valley Cancer Institute and Research Center /ID# 201201 | |
Eugene, Oregon, United States, 97401-6043 | |
United States, South Carolina | |
Prisma Health Cancer Inst - Eastside /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 - Northeast Texas /ID# 201211 | |
Tyler, Texas, United States, 75702 | |
United States, Washington | |
Northwest Cancer Specialists, P.C. /ID# 201198 | |
Vancouver, Washington, United States, 98684 |
Study Director: | ABBVIE INC. | AbbVie |
Documents provided by AbbVie:
Responsible Party: | AbbVie |
ClinicalTrials.gov Identifier: | NCT03406156 |
Other Study ID Numbers: |
M16-788 |
First Posted: | January 23, 2018 Key Record Dates |
Results First Posted: | November 3, 2022 |
Last Update Posted: | November 3, 2022 |
Last Verified: | October 2022 |
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) |
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/ |
URL: | https://vivli.org/ourmember/abbvie/ |
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 |
Cancer Chronic Lymphocytic Leukemia 17p Deletion Debulking Obinutuzumab |
Bendamustine Tumor lysis syndrome Venetoclax Small Lymphocytic Lymphoma |
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 Venetoclax Bendamustine Hydrochloride Obinutuzumab Antineoplastic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological |