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Chronic Lymphocytic LeucemiaPhase 2NCT02345863

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

A Phase 2 study testing Bendamustine, GA101 and Ibrutinib in people with Chronic Lymphocytic Leucemia, run by German CLL Study Group at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leucemia
What is being tested?
Bendamustine, GA101 and Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
1 siteGermany
Study dates
16 Jan 2015to 29 Mar 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • Creatinine clearance ≥ 30 ml/min
  • Adequate hematologic function
  • Adequate liver function
  • Negative serological testing for hepatitis B, hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
  • Age at least 18 years
  • Eastern Cooperative Oncology Group [ECOG] status 0 - 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

Who cannot join

  • Transformation of CLL
  • Known central nervous system (CNS) involvement
  • Patients with a history of confirmed progressive multifocal leukoencephalopathy [PML]
  • Malignancies other than CLL currently requiring systemic therapies
  • Uncontrolled infection requiring systemic treatment
  • Use of investigational agents which would interfere with the study drug within 28 days prior to registration
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  • 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)
  • Known hypersensitivity to GA101, ibrutinib or any of the excipients
  • Requirement of treatment with strong cytochrome P450 3A4 [CYP3A4] -inhibitors/-inducers or anticoagulant with warfarin or phenprocoumon (marcumar)
  • History of stroke or intracranial hemorrhage within 6 months prior to registration
  • 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 a minimum of 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

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • German CLL Study Group

    Cologne, 50935

Other trials in Germany

About this study

Official title: 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.

Read the 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.

Being tested
Bendamustine, GA101, Ibrutinib
Keywords
CLL

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BendamustineDrug

    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.

  • GA101Drug

    Also called Obinutuzumab

    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

  • IbrutinibDrug

    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

Study groups in NCT02345863
Study groupRoleWhat they receive
Bendamustine + GA101 + IbrutinibExperimentalBendamustine 70mg/m² i´v GA101: 1000 mg iv Ibrutinib: 420 mg po daily
Receives: Drug: Bendamustine; Drug: GA101; Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate (ORR)

    proportion of patients responding according to international working Group on chronic lymphocytic leukemia criteria

    Measured: 84 days after first dose of last induction cycle

Secondary outcomes (2)

  1. Safety: Adverse events (AEs) and adverse events of special interest (AESI)

    Type, frequency, and severity of adverse events (AEs) and adverse events of special interest (AESI) and their relationship to study treatment.

    Measured: up to 48 months after first dose of study drug

  2. minimal residual disease (MRD)

    Rate of MRD responses in peripheral blood measured by immunophenotyping

    Measured: final restaging and during maintenance

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2015 (estimated)
  2. Study start16 Jan 2015
  3. Primary completion22 Aug 2016
  4. Study completion29 Mar 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02345863
Sponsor's protocol ID
CLL2-BIG
Other IDs
2014-000569-35, 2014
Status last verified
May 2019
First submitted
12 Jan 2015
Last updated
8 May 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • von Tresckow J, Cramer P, Bahlo J, Robrecht S, Langerbeins P, Fink AM, Al-Sawaf O, Illmer T, Klaproth H, Estenfelder S, Ritgen M, Fischer K, Wendtner CM, Kreuzer KA, Stilgenbauer S, Bottcher S, Eichhorst BF, Hallek M. CLL2-BIG: sequential treatment with bendamustine, ibrutinib and obinutuzumab (GA101) in chronic lymphocytic leukemia. Leukemia. 2019 May;33(5):1161-1172. doi: 10.1038/s41375-018-0313-8. Epub 2018 Dec 19.

    PubMed 30568174

  • Langerbeins P, Giza A, Robrecht S, Cramer P, von Tresckow J, Al-Sawaf O, Fink AM, Furstenau M, Kutsch N, Simon F, Goede V, Hoechstetter M, Niemann CU, da Cunha-Bang C, Kater A, Dubois J, Gregor M, Staber PB, Tausch E, Schneider C, Stilgenbauer S, Eichhorst B, Fischer K, Hallek M. Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies. Blood. 2024 Jun 20;143(25):2588-2598. doi: 10.1182/blood.2023022564.

    PubMed 38620092

  • Cramer P, Tausch E, von Tresckow J, Giza A, Robrecht S, Schneider C, Furstenau M, Langerbeins P, Al-Sawaf O, Pelzer BW, Fink AM, Fischer K, Wendtner CM, Eichhorst B, Kneba M, Stilgenbauer S, Hallek M. Durable remissions following combined targeted therapy in patients with CLL harboring TP53 deletions and/or mutations. Blood. 2021 Nov 11;138(19):1805-1816. doi: 10.1182/blood.2020010484.

    PubMed 34086865

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bendamustine, GA101 and Ibrutinib in people with Chronic Lymphocytic Leucemia, run by German CLL Study Group at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) (time frame: 84 days after first dose of last induction cycle). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02345863, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2019.

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