Uni-Koeln-1776

University of Cologne

Albertus Magnus-Platz, Köln, Germany, 50923

Trial Coordination Center, German Hodgkin Study Group, 0049 22147888200, ghsg@uk-koeln.de

Trial Coordination Center, German Hodgkin Study Group, 0049 22147888200, ghsg@uk-koeln.de

No

No

No

Final

11 Jan 2021

Yes

20 May 2020

Yes

20 May 2020

Yes

To establish a novel, non-toxic treatment option for patients with relapsed nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL).

Written informed consent prior to study entry; 2-stage design with comprehensive interim risk-benefit assessment and formal futility criterion after stage 1;

26 Aug 2016

No

Yes

Germany: 16

16

16

0

0

0

0

0

0

15

1

0

Stage 1 (overall period)

Not applicable

Ibrutinib

Imbruvica (R)

Tablet, Capsule

Oral use

Patients receive continuous 21-day cycles of ibrutinib with a daily dose of 560 mg (i.e. 4 capsules p.d.). The whole dose should be taken at one certain timepoint. Treatment with ibrutinib should be held temporarily, i.e. in case grade IV neutropenia or thrombocytopenia or grade III neutropenia with fever and infection or grade III/IV non-hematological adverse events occur. After recovery from any of such adverse events, ibrutinib should be restarted at full dose after the first occurrence of the event, at 420 mg after the second occurrence of the same event and at 280 mg after the third occurrence of the same event. After the fourth occurrence of the same event, ibrutinib should be discontinued permanently. Ibrutinib treatment must be terminated after a maximum number of 20 cycles.

Stage 1 (overall period)

Full analysis set

The full analysis set (FAS) consists of all patients who receive at least one daily dose (partial or full dose) of ibrutinib.

Safety analysis set

The safety analysis set (SAS) consists of all patients of the FAS who had at least one valid post-baseline safety assessment.

Disease stabilization/response analysis set

The disease stabilization/response anlysis set (DSR) consists of all patients in the FAS who do not have any major protocol deviation (e.g. violation of inclusion/exclusion criteria) and complete at least six 21-day cycles of single agent ibrutinib unless discontinuation for early disease progression at any time or due to adverse events after at least four cycles of ibrutinib treatment. All patients in the DSR set must have been evaluated for diesease stabilization/response at least once, i.e. at the first planned interim staging according to protocol or earlier in case of disease progression.

Experimental

Full analysis set

The full analysis set (FAS) consists of all patients who receive at least one daily dose (partial or full dose) of ibrutinib.

Safety analysis set

The safety analysis set (SAS) consists of all patients of the FAS who had at least one valid post-baseline safety assessment.

Disease stabilization/response analysis set

The disease stabilization/response anlysis set (DSR) consists of all patients in the FAS who do not have any major protocol deviation (e.g. violation of inclusion/exclusion criteria) and complete at least six 21-day cycles of single agent ibrutinib unless discontinuation for early disease progression at any time or due to adverse events after at least four cycles of ibrutinib treatment. All patients in the DSR set must have been evaluated for diesease stabilization/response at least once, i.e. at the first planned interim staging according to protocol or earlier in case of disease progression.

Disease stabilization/response rate after six 21-day cycles of ibrutinib. A complete remission (CR), partial remission (PR), and no change (NC) as treatment response according to the central review evaluation panel (CREP) were counted as disease stabilization, i.e. success for the primary endpoint. The following cases were counted as failures for the primary efficacy endpoint: - Progressive disease (PD) confirmed by CREP - CR/PR/NC could not be confirmed by the CREP. According to the protocol, the null hypothesis H0: DSR ≤ 70% was to be testes in a 2-stage design. The trial was terminated after stage 1. Thus, only descriptive analyses of the primary endpoint in the stage-1 DSR set were done.

Primary

The first interim staging was conducted after six treatment cycles (within the first week of cycle 7) or earlier in case of suspected progression. Patients who achieve at least disease stabilization according to the CREP continue study treatment.

AEs were assessed from start of study treatment up to 30 days after end of treatment have to be reported. AEs that occur later than 30 days after the end of treatment have to be reported in case the causality is judged at least as “possible”.

All serious adverse events (SAE) have to be reported as long as the patient is in the trial, independent of the investigator´s opinion whether there is a causal relationship with the study therapy or not.

10.2

Experimental