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

• Status: Completed
• Trial end date: 2019-03-29
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: German CLL Study Group
• Collaborators: Hoffmann-La Roche; Janssen-Cilag Ltd.
• Treatments: Bendamustine Hydrochloride; Obinutuzumab

Criteria

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