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

NCT02345863 | Completed Phase 2

• 2 other identifiers: CLL2-BIG2014-000569-35
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Lymphocytic Leucemia

Keywords

CLL

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

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

  84 days after first dose of last induction cycle

Secondary Outcomes (2)

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

  up to 48 months after first dose of study drug

• minimal residual disease (MRD)

  final restaging and during maintenance

Study Arms (1)

Bendamustine + GA101 + Ibrutinib

EXPERIMENTAL

Bendamustine 70mg/m² i´v GA101: 1000 mg iv Ibrutinib: 420 mg po daily

Drug: Bendamustine; Drug: GA101; Drug: Ibrutinib

Interventions

Bendamustine DRUG

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.

Bendamustine + GA101 + Ibrutinib

GA101 DRUG

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

Also known as: Obinutuzumab

Bendamustine + GA101 + Ibrutinib

Ibrutinib DRUG

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

Bendamustine + GA101 + Ibrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• German CLL Study Group: lead
• Hoffmann-La Roche: collaborator
• Janssen-Cilag Ltd.: collaborator

Study Sites (1)

German CLL Study Group

Cologne, 50935, Germany

Location

Related Publications (3)

• 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.

  PMID: 30568174 RESULT

• 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.

  PMID: 38620092 DERIVED

• 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.

  PMID: 34086865 DERIVED

MeSH Terms

Interventions

Bendamustine Hydrochloride; obinutuzumab; ibrutinib

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Julia von Tresckow, Dr. med.

  German CLL Study Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2015
• First Posted: January 26, 2015
• Study Start: January 16, 2015
• Primary Completion: August 22, 2016
• Study Completion: March 29, 2019
• Last Updated: May 8, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)