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Sequential Regimen of Bendamustine-Debulking Followed by ABT-199 and GA101-Induction and -Maintenance in CLL (CLL2-BAG)

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ClinicalTrials.gov Identifier: NCT02401503
Recruitment Status : Active, not recruiting
First Posted : March 27, 2015
Last Update Posted : October 17, 2018
Sponsor:
Collaborators:
Hoffmann-La Roche
AbbVie
Information provided by (Responsible Party):
German CLL Study Group

Tracking Information
First Submitted Date  ICMJE March 24, 2015
First Posted Date  ICMJE March 27, 2015
Last Update Posted Date October 17, 2018
Actual Study Start Date  ICMJE May 6, 2015
Actual Primary Completion Date December 13, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2015)
Overall response rate (ORR) [ Time Frame: 84 days after start of the last cycle of induction therapy ]
Proportion of patients responding according to international working Group on chronic lymphocytic leukemia criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02401503 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2015)
  • Adverse Events (AEs) and adverse events of special interest (AESI) [ Time Frame: up to 40 months after first dose of study drug ]
    Type, frequency and severity of adverse events (AEs) and adverse events of special interest (AESI) and their relationship to study treatment
  • Rate of minimal residual disease (MRD) [ Time Frame: up to 40 months ]
    Rate of MRD responses in peripheral blood measured by immunophenotyping
Original Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2015)
  • Adverse Events (AEs) and adverse events of special interest (AESI) [ Time Frame: up to 40 months after first dose of study drug ]
    Type, frequency and sevirity of adverse events (AEs) and adverse events of special interest (AESI) and their relationship to study treatment
  • Rate of minimal residual disease (MRD) [ Time Frame: up to 40 months ]
    Rate of MRD responses in peripheral blood measured by immunophenotyping
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sequential Regimen of Bendamustine-Debulking Followed by ABT-199 and GA101-Induction and -Maintenance in CLL (CLL2-BAG)
Official Title  ICMJE A Prospective, Open-label, Multicenter Phase-II Trial to Evaluate the Efficacy and Safety of a Sequential Regimen of Bendamustine Followed by GA101 and ABT-199 Followed by ABT-199 and GA101 Maintenance in CLL Patients
Brief Summary The CLL2-BAG-trial is a prospective, open-label, multicenter phase-II trial to evaluate the efficacy and safety of a sequential regimen of a debulking with Bendamustine followed by an induction with GA101 (obinutuzumab) and ABT-199 (venetoclax, GDC-0199) followed by ABT-199 and GA101-maintenance in CLL patients
Detailed Description In the CLL2-BAG-trial, a total of 62 patients of an allcomer CLL population (irrespective of physical fitness, previous therapies and prognostic factors) with an indication for treatment will be included. Patient will receive 2 cycles of debulking treatment with Bendamustine unless contraindications (e.g. refractoriness) are present or a debulking is not indicated due to a low tumor load. Afterwards, 6 cycles of induction treatment with GA101 (obinutuzumab, 3 doses in the first cycle and monthly in cycles 2-6) and ABT-199 (venetoclax, continuously starting in cycle 2 with a low dose escalation) will be applied. The primary endpoint overall response rate will be assessed at final restaging (2 months after end of induction treatment). Patients benefitting from treatment receive further therapy with GA101 (3 monthly) and ABT-199 (continuously) in a maintenance phase for up to 24 months. Maintenance treatment will be stopped in case of achievement of a complete remission and confirmation of MRD (minimal residual disease) negativity in peripheral blood or if unacceptable toxicity or progression occurs.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Lymphocytic Leucemia
Intervention  ICMJE
  • Drug: Bendamustine
    Debulking: Cycles 1-2, d1 & 2: 70mg/m² i.v.
  • Drug: GA101
    Induction: Cycle 1: d1: 100mg, d1(or 2): 900mg, d8 & 15: 1000mg; Cycle 2-6: d1: 1000mg Maintenance: Cycles 1-8 (Duration 12 weeks): d1: 1000mg
    Other Name: Obinutuzumab
  • Drug: ABT-199
    Induction: Cycle 2: d1-7: 20mg, d8-14: 50mg, d15-21: 100mg, d22-28: 200mg; Cycle 3-6: d1-28: 400mg Maintenance: Cycles 1-8 (Duration 12 weeks): d1-84: 400mg
    Other Name: Venetoclax, GDC-0199
Study Arms  ICMJE Experimental: Bendamustine + GA101 + ABT-199
Bendamustine: 70mg/m² i.v. GA101: 1000 mg i.v. ABT-199: 20 - 400 mg p.o.
Interventions:
  • Drug: Bendamustine
  • Drug: GA101
  • Drug: ABT-199
Publications * Cramer P, von Tresckow J, Bahlo J, Robrecht S, Langerbeins P, Al-Sawaf O, Engelke A, Fink AM, Fischer K, Tausch E, Seiler T, Fischer von Weikersthal L, Hebart H, Kreuzer KA, Böttcher S, Ritgen M, Kneba M, Wendtner CM, Stilgenbauer S, Eichhorst B, Hallek M. Bendamustine followed by obinutuzumab and venetoclax in chronic lymphocytic leukaemia (CLL2-BAG): primary endpoint analysis of a multicentre, open-label, phase 2 trial. Lancet Oncol. 2018 Sep;19(9):1215-1228. doi: 10.1016/S1470-2045(18)30414-5. Epub 2018 Aug 13.

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 23, 2015)
66
Original Estimated Enrollment  ICMJE
 (submitted: March 26, 2015)
62
Estimated Study Completion Date  ICMJE April 2020
Actual Primary Completion Date December 13, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • documented chronic lymphocytic leukemia (CLL) requiring treatment according to International Working Group on CLL (iwCLL) criteria
  • adequate renal function: a creatinine clearance ≥30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24 hr. urine collection
  • adequate hematologic function: platelets ≥ 25.000/µl, neutrophils ≥ 1.000/µl and hemoglobin ≥8.0 g/dL, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration)
  • adequate liver function: total bilirubin ≤2x, aspartate aminotransferase (AST) / alanin aminotransferase (ALT) ≤2.5x the institutional upper Limit of normal (ULN) value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome
  • negative serological testing for hepatitis B, negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
  • age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2, ECOG 3 is only permitted if related to CLL
  • life expectancy ≥ 6 months
  • ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

  • transformation of CLL (i.e. Richter's transformation, prolymphocytic leukemia)
  • known central nervous system (CNS) involvement
  • confirmed progressive multifocal leukoencephalopathy (PML)
  • malignancies other than CLL currently requiring systemic therapies
  • uncontrolled infection requiring systemic treatment
  • any comorbidity or organ system impairment rated with a cumulative illness rating scale (CIRS) score of 4, excluding the eyes/ears/nose/throat/larynx organ system or any other life-threatening illness, medical condition or organ system dysfunction that - in the investigator´s opinion - could compromise the patients safety or interfere with the absorption or metabolism of the study drugs (e.g, inability to swallow tablets or impaired resorption in the gastrointestinal tract)
  • requirement of therapy with strong cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors/inducers or anticoagulant with warfarin, phenprocoumon (marcumar) or other vitamin K-antagonists
  • use of investigational agents within 28 days prior to registration
  • known hypersensitivity to GA101 (obinutuzumab), ABT-199 (venetoclax, GDC-0199) or any of the excipients
  • pregnant women and nursing mothers
  • fertile men or women of childbearing potential unless surgically sterile or ≥ 2 years after the onset of menopause, or willing to use two methods of reliable contraception including one highly effective (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 18 months after end of study treatment
  • vaccination with a live vaccine ≤28 days prior to registration
  • legal incapacity
  • prisoners or subjects who are institutionalized by regulatory or court order
  • persons who are in dependence to the sponsor or an investigator
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02401503
Other Study ID Numbers  ICMJE CLL2-BAG
2014-000580-40 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party German CLL Study Group
Study Sponsor  ICMJE German CLL Study Group
Collaborators  ICMJE
  • Hoffmann-La Roche
  • AbbVie
Investigators  ICMJE
Principal Investigator: Paula Cramer, Dr. med. German CLL Study Group
PRS Account German CLL Study Group
Verification Date October 2018

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