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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. Read our disclaimer for details.
 
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
Sponsor:
Information provided by (Responsible Party):
AbbVie

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.

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 ...

Detailed Description:
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.

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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
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:
  • Venclexta
  • ABT-199
  • GDC-0199

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:
  • Venclexta
  • ABT-199
  • GDC-0199




Primary Outcome Measures :
  1. 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.

  2. 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)
    • 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.



Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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 ).



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.


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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
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

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


Locations
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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
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: ABBVIE INC. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Study Protocol  [PDF] December 19, 2019
Statistical Analysis Plan  [PDF] October 8, 2019

Additional Information:
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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/

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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:
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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