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Chronic Lymphocytic LeukemiaPhase 2NCT02689141

Sequential Regimen of Bendamustin-Debulking Followed by Ofatumumab and Ibrutinib in CLL Patients (CLL2-BIO)

A Phase 2 study testing Bendamustine, Ofatumumab and Ibrutinib in people with Chronic Lymphocytic Leukemia, 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, multicentre phase-II trial to evaluate the efficacy and safety of a sequential regimen of bendamustine followed by ofatumumab and ibrutinib followed by ibrutinib and ofatumumab 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 Leukemia
What is being tested?
Bendamustine, Ofatumumab and Ibrutinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
1 siteGermany
Study dates
4 Feb 2016to 6 Feb 2020
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 International Working Group on CLL (iwCLL) criteria
  • 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-BIO trial:
  • chemotherapy within ≥ 28 days
  • antibody treatment within ≥ 14 days
  • kinase inhibitors, Bcl-2-antagonists or immunomodulatory agents within ≥ 3 days
  • corticosteroids may be applied until the start of the BIO-regimen, these have to be reduced to an equivalent of ≤ 20 mg prednisolone during treatment
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  • Adequate hematologic function as indicated by a platelet count ≥ 25 x 109/L, a neutrophil count ≥ 1,0 x 109/L and a hemoglobin value ≥ 8.0 g/dL, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration)
  • Adequate renal function as indicated by a creatinine clearance ≥ 30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24 hrs urine collection
  • Adequate liver function as indicated by a 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 antibody 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 (e.g. due to anemia or severe constitutional symptoms)
  • 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 (i.e. Richter's transformation, pro-lymphocytic leukemia)
  • Known central nervous system (CNS) involvement
  • Patients with confirmed progressive multifocal leukoencephalopathy (PML)
  • Malignancies other than CLL currently requiring systemic therapy
  • 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)
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  • Use of investigational agents which might interfere with the study drug within 3 days prior to Registration
  • Known hypersensitivity to ofatumumab, ibrutinib or any of the excipients Please note: Patients with a known hypersensitivity to bendamustine are allowed to participate but will not receive a debulking with bendamustine
  • Requirement of treatment with strong CYP3A4-inhibitors/-inducers or anticoagulant with phenprocoumon (marcumar), warfarin, or other vitamin k antagonists
  • History of stroke or intracranial hemorrhage within 6 months prior to registration
  • Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment and monthly during debulking, induction and maintenance therapy)
  • 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 12 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

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: Prospective, Open-label, Multicentre Phase-II Trial to Evaluate Efficacy and Safety of a Sequential Regimen of Bendamustine Followed by Ofatumumab and Ibrutinib Followed by Ibrutinib and Ofatumumab Maintenance in CLL Patients

A prospective, open-label, multicentre phase-II trial to evaluate the efficacy and safety of a sequential regimen of bendamustine followed by ofatumumab and ibrutinib followed by ibrutinib and ofatumumab maintenance in CLL patients.

Read the detailed description

In the CLL2-BIO 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 ofatumumab 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 BIO 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, Ofatumumab, Ibrutinib
Keywords
chronic lymphocytic leukemia CLL, untreated chronic lymphocytic leukemia, relapsed chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, B-Cell

What participants receive

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

  • BendamustineDrug

    Debulking: Cycles 1 - 2, d1 \& 2: 70 mg/m2 i.v.

  • OfatumumabDrug

    Induction:

    Cycle 1: Day 1 300 mg i.v.; Day 8 1000 mg i.v.; Day 15 1000 mg i.v. Cycle 2-6: Day 1 1000 mg i.v.

    Maintenance: After the induction ofatumumab iv 1000 mg every three months will be continued.

    Cycle 1-8: Day 1 1000 mg i.v.

  • IbrutinibDrug

    Induction: Cycle 2-6: d1-28: 420 mg p.o. Maintenance: After the induction ibrutinib p.o. 420 mg daily will be continued. Cycle 1-8: d1-84: 420 mg p.o.

Study groups in NCT02689141
Study groupRoleWhat they receive
Bendamustine + Ofatumumab + IbrutinibExperimentalBendamustine: 70mg/m² i.v. Ofatumumab: 1000 mg i.v. Ibrutinib: 420 mg po
Receives: Drug: Bendamustine; Drug: Ofatumumab; 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: up to 48 months after first dose of study drug

Timeline

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

  1. First posted23 Feb 2016 (estimated)
  2. Study start4 Feb 2016
  3. Primary completion13 Jul 2017
  4. Study completion6 Feb 2020

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
NCT02689141
Sponsor's protocol ID
CLL2-BIO
Other IDs
2014-000590-39, 2014
Status last verified
Jun 2020
First submitted
29 Jan 2016
Last updated
11 Jun 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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

  • Cramer P, Tresckow JV, Robrecht S, Bahlo J, Furstenau M, Langerbeins P, Pflug N, Al-Sawaf O, Heinz WJ, Vehling-Kaiser U, Durig J, Tausch E, Hensel M, Sasse S, Fink AM, Fischer K, Kreuzer KA, Bottcher S, Ritgen M, Kneba M, Wendtner CM, Stilgenbauer S, Eichhorst B, Hallek M. Bendamustine, followed by ofatumumab and ibrutinib in chronic lymphocytic leukemia (CLL2-BIO): primary endpoint analysis of a multicenter, open-label phase-II trial. Haematologica. 2021 Feb 1;106(2):543-554. doi: 10.3324/haematol.2019.223693.

    PubMed 32107341

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bendamustine, Ofatumumab and Ibrutinib in people with Chronic Lymphocytic Leukemia, 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 18 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 11 Jun 2020. 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 NCT02689141, 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 11 Jun 2020.

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