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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-04

Study Completion Date

2020-02-06

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

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

NCT02345863

Chronic Lymphocytic Leucemia

COMPLETED PHASE2

Sequential Regimen of Bendamustine-Debulking Followed by CAL-101 and GA101-Induction and -Maintenance in CLL (CLL2-BCG)

NCT02445131

Chronic Lymphocytic Leucemia

COMPLETED PHASE2

CLLR3: Bendamustine + GA101 (BG) in Relapsed or Refractory CLL Followed by GA101 Maintenance for Responding Patients

NCT02320383

Chronic Lymphocytic Leucemia

UNKNOWN PHASE2

A Study Evaluating the Efficacy of Obinutuzumab and Bendamustine Treatment in Participants With Refractory or Relapsed Chronic Lymphocytic Leukemia

NCT02071225

Chronic Lymphocytic Leukemia

COMPLETED PHASE2

Ofatumumab Plus Bendamustine in Frontline and Relapsed Chronic Lymphocytic Leukaemia (CLL)

NCT01520922

Chronic Lymphocytic Leukemia (CLL) Leukaemia, Lymphocytic, Chronic

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Chronic Lymphocytic Leukemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Bendamustine + Ofatumumab + Ibrutinib

Bendamustine: 70mg/m² i.v. Ofatumumab: 1000 mg i.v. Ibrutinib: 420 mg po

Group Type EXPERIMENTAL

Bendamustine

Intervention Type DRUG

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

Ofatumumab

Intervention Type DRUG

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.

Ibrutinib

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Bendamustine

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

Intervention Type DRUG

Ofatumumab

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.

Intervention Type DRUG

Ibrutinib

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.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. 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
2. 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)
3. 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
4. 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
5. Negative serological testing for hepatitis B, negative testing for hepatitis-C RNA and negative HIV antibody test within 6 weeks prior to registration
6. Age ≥ 18 years
7. 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)
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 (i.e. Richter's transformation, pro-lymphocytic leukemia)
2. Known central nervous system (CNS) involvement
3. Patients with confirmed progressive multifocal leukoencephalopathy (PML)
4. Malignancies other than CLL currently requiring systemic therapy
5. Uncontrolled infection requiring systemic treatment
6. 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)
7. Use of investigational agents which might interfere with the study drug within 3 days prior to Registration
8. 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
9. Requirement of treatment with strong CYP3A4-inhibitors/-inducers or anticoagulant with phenprocoumon (marcumar), warfarin, or other vitamin k antagonists
10. History of stroke or intracranial hemorrhage within 6 months prior to registration
11. 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)
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 12 months after end of study treatment.
13. Vaccination with a live vaccine ≤ 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No