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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

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ClinicalTrials.gov Identifier: NCT03406156
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : July 29, 2019
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE January 16, 2018
First Posted Date  ICMJE January 23, 2018
Last Update Posted Date July 29, 2019
Actual Study Start Date  ICMJE August 10, 2018
Estimated Primary Completion Date April 3, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2018)
  • 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).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03406156 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 12, 2018)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2018)
  • 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. 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lymphocytic Leukemia (CLL)
  • Small Lymphocytic Lymphoma (SLL)
Intervention  ICMJE
  • Drug: Obinutuzumab
    intravenous
    Other Name: Gazyva
  • Drug: Bendamustine
    intravenous
    Other Name: Bendeka
  • Drug: Venetoclax
    tablet
    Other Names:
    • Venclexta
    • ABT-199
    • GDC-0199
Study Arms  ICMJE 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.

Interventions:
  • Drug: Obinutuzumab
  • Drug: Bendamustine
  • Drug: Venetoclax
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 26, 2019)
120
Original Estimated Enrollment  ICMJE
 (submitted: January 16, 2018)
100
Estimated Study Completion Date  ICMJE July 16, 2024
Estimated Primary Completion Date April 3, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ABBVIE CALL CENTER 847.283.8955 abbvieclinicaltrials@abbvie.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03406156
Other Study ID Numbers  ICMJE M16-788
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP