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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

NCT03406156

Description:

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.

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: M16-788
  • NCT ID: NCT03406156

Conditions

  • Chronic Lymphocytic Leukemia (CLL)

Interventions

DrugSynonymsArms
ObinutuzumabGazyvaObinutuzumab +/- bendamustine then obinutuzumab + venetoclax
BendamustineTreandaObinutuzumab +/- bendamustine then obinutuzumab + venetoclax
VenetoclaxVenclexta, ABT-199, GDC-0199Obinutuzumab +/- bendamustine then obinutuzumab + venetoclax

Purpose

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,

Trial Arms

NameTypeDescriptionInterventions
Obinutuzumab +/- bendamustine then obinutuzumab + venetoclaxExperimentalDebulking 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.
  • Obinutuzumab
  • Bendamustine
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Adequate hematology, kidney and liver function as described in the protocol.

          -  Diagnosis of previously untreated chronic lymphocytic leukemia (CLL) 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 to aggressive non-Hodgkin's lymphoma or
             Hodgkin's lymphoma).

          -  Prolymphocytic leukemia.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Low tumor burden is defined by peripheral lymphocyte counts of < 25,000 and all lymph nodes < 5 cm per CT scans.

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Up to approximately 3.5 years after initial dose of study drug
Safety Issue:
Description: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.
Measure:Duration of Response (DoR)
Time Frame:Up to approximately 3.5 years after initial dose of study drug
Safety Issue:
Description: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).
Measure:Progression-Free Survival (PFS)
Time Frame:Up to approximately 3.5 years after initial dose of study drug
Safety Issue:
Description: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.
Measure:Time to Progression (TTP)
Time Frame:Up to approximately 3.5 years after initial dose of study drug
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 3.5 years after initial dose of study drug
Safety Issue:
Description: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.
Measure:Minimal Residual Disease (MRD) Negativity Rate
Time Frame:Up to approximately 3.5 years after initial dose of study drug
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AbbVie

Trial Keywords

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

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