Sequential Regimen of Bendamustin [B] Followed by GA101 and Ibrutinib [I] in CLL Patients

May 7, 2019 updated by: German CLL Study Group

A Prospective, Open-label, Multicenter Phase-II Trial to Evaluate the Efficacy and Safety of a Sequential Regimen of Bendamustine Followed by GA101 and Ibrutinib (BIG) Followed by GA101 and Ibrutinib Maintenance in CLL Patients (CLL2-BIG Protocol)

A prospective, open-label, multicenter Phase-II trial to evaluate the efficacy and safety of a sequential regimen of Bendamustine followed by GA101 and Ibrutinib followed by Ibrutinib and GA101 maintenance in CLL patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In the CLL2-BIG trial an allcomer CLL population with indication for treatment will be included.

Patient will receive 2 cycles of debulking treatment with bendamustin unless contraindications are existing or debulking is not indicated.

Afterwards 6 cycles of induction therapy with GA101 and ibrutinib will be applied, each with a duration of 28 days. Primary endpoint overall Response rate will be assessed at final restaging.

Patients benefitting from BIG treatment will enter the maintenance phase of the trial. Maintenance treatment will be continued if no unacceptable toxicity occurs until three months after negativity of minimal residual disease [MRD] is achieved in peripheral blood in patients with (clinical) complete response (CR) or (clinical) incomplete complete response [CRi] (confirmed by 2 consecutive testings of MRD within 3 months), progression of CLL, start of a subsequent therapy or up to 8 cycles of maintenance (each cycle with a duration of 84 calendar days = 3 months), whichever occurs first.

Study Type

Interventional

Enrollment (Actual)

66

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Cologne, Germany, 50935
        • German CLL Study Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. documented CLL requiring treatment (irrespective if first- or relapse treatment) according to the criteria of the international Workshop of CLL [iwCLL]

    In case of previously treated patients, these must have recovered from acute toxicities and treatment regimen must be stopped within the following time periods before start of the study treatment in the CLL2-BIG trial:

    • chemotherapy within ≥ 28 days
    • antibody treatment within ≥ 14 days
    • kinase inhibitors, B-cell-lymphoma 2 [BCL2] -antagonists or immunomodulatory agents within ≥ 3 days
    • corticosteroids may be applied until the start of the BIG-regimen, these have to be reduced to an equivalent of ≤ 20mg prednisolon during treatment
  2. Creatinine clearance ≥ 30 ml/min
  3. Adequate hematologic function
  4. Adequate liver function
  5. Negative serological testing for hepatitis B, hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
  6. Age at least 18 years
  7. Eastern Cooperative Oncology Group [ECOG] status 0 - 2; ECOG 3 is only permitted if related to CLL
  8. Life expectancy ≥ 6 months
  9. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

  1. Transformation of CLL
  2. Known central nervous system (CNS) involvement
  3. Patients with a history of confirmed progressive multifocal leukoencephalopathy [PML]
  4. Malignancies other than CLL currently requiring systemic therapies
  5. Uncontrolled infection requiring systemic treatment
  6. Use of investigational agents which would interfere with the study drug within 28 days prior to registration
  7. 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 comprise 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)
  8. Known hypersensitivity to GA101, ibrutinib or any of the excipients
  9. Requirement of treatment with strong cytochrome P450 3A4 [CYP3A4] -inhibitors/-inducers or anticoagulant with warfarin or phenprocoumon (marcumar)
  10. History of stroke or intracranial hemorrhage within 6 months prior to registration
  11. Pregnant women and nursing mothers
  12. 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.
  13. Vaccination with a live vaccine a minimum of 28 days prior to registration
  14. Legal incapacity
  15. Prisoners or subjects who are institutionalized by regulatory or court order
  16. Persons who are in dependence to the sponsor or an investigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bendamustine + GA101 + Ibrutinib

Bendamustine 70mg/m² i´v

GA101: 1000 mg iv

Ibrutinib: 420 mg po daily
Drug: Bendamustine

Debulking:

2 cycles of Bendamustine (70 mg/m² iv) will be administered before induction unless a contraindication is existing or it is not clinically indicated.

Drug: GA101

Induction

GA101 iv infusion:

Cycle 1: Day 1 100 mg Day 1 (or 2) 900 mg Day 8 1000 mg Day 15 1000 mg Cycle 2-6: Day 1 1000 mg

Maintenance After the induction ibrutinib po 420 mg daily and GA101 iv 1000 mg every three months will be continued.

GA101: Cycle 1-8 Day 1 1000 mg

Other Names:
  • Obinutuzumab
Drug: Ibrutinib

Ibrutinib will be administered as a daily oral dosage of 420 mg starting on cycle 2 day 1.

Cycle 2-6: Day 1 420 mg daily

Maintenance After the induction ibrutinib po 420 mg daily and GA101 iv 1000 mg every three months will be continued.

Ibrutinib: Cycle 1-8 420 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: 84 days after first dose of last induction cycle
proportion of patients responding according to international working Group on chronic lymphocytic leukemia criteria
84 days after first dose of last induction cycle

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety: Adverse events (AEs) and adverse events of special interest (AESI)
Time Frame: up to 48 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.
up to 48 months after first dose of study drug
minimal residual disease (MRD)
Time Frame: final restaging and during maintenance
Rate of MRD responses in peripheral blood measured by immunophenotyping
final restaging and during maintenance

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German CLL Study Group

Collaborators

Hoffmann-La Roche
Janssen-Cilag Ltd.

Investigators

  • Principal Investigator: Julia von Tresckow, Dr. med., German CLL Study Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 16, 2015

Primary Completion (Actual)

August 22, 2016

Study Completion (Actual)

March 29, 2019

Study Registration Dates

First Submitted

January 12, 2015

First Submitted That Met QC Criteria

January 23, 2015

First Posted (Estimate)

January 26, 2015

Study Record Updates

Last Update Posted (Actual)

May 8, 2019

Last Update Submitted That Met QC Criteria

May 7, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLL2-BIG
  • 2014-000569-35 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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