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SNCTP000004689 | NCT04608318 | BASEC2021-01861

Eine prospektive, randomisierte, unverblindete, multizentrische Phase-III-Studie zum Vergleich der Wirksamkeit und Sicherheit von Ibrutinib Monotherapie gegen eine zeitlich begrenzte Therapie mit Venetoclax plus Obinutuzumab oder Ibrutinib plus Venetoclax bei Patienten mit bislang unbehandelter chronisch lymphatischer Leukämie (CLL) - CLL17

Data source: BASEC (Imported from 28.03.2024), WHO (Imported from 20.03.2024)
Changed: Mar 20, 2024, 1:00 AM
Disease category: Leukemia

Brief description of trial (Data source: BASEC)

In dieser klinischen Prüfung (CLL17-Studie) werden drei verschiedene Behandlungsarme bestehend aus Ibrutinib und Venetoclax sowie Obinutuzumab in unterschiedlichen Kombinationen und mit unterschiedlicher Behandlungsdauer miteinander verglichen. Aktuell ist unklar, ob eine zeitlich unbegrenzte Therapie mit Ibrutinib und eine zeitlich begrenzte Therapie mit der Kombination von zwei Präparaten (d.h. Venetoclax plus Obinutuzumab oder Ibrutinib plus Venetoclax) gleich wirksam sind. Um diese Frage zu beantworten ist ein Vergleich der Behandlungsarme wie in der CLL17-Studie erforderlich. Anhand der Ergebnisse wird man in Zukunft entscheiden können, für welche Patienten welche dieser Therapien besser geeignet ist. Die kontinuierliche Therapie mit Ibrutinib ist in der EU und der Schweiz zur Therapie der CLL zugelassen. Die zeitlich limitierte Therapie mit der Kombination Venetoclax + Obinutuzumab ist in der EU aber nicht in der Schweiz zugelassen. Die zeitlich limitierte Therapie mit Ibrutinib + Venetoclax ist noch keine zugelassene Therapie-Kombination. Bei dieser Studie erhalten alle eingeschlossenen Patienten einen der drei Behandlungsarme. Welche Behandlung Sie erhalten, entscheidet der Zufall per Computerauswahl (dieses Verfahren wird „Randomisierung“ genannt). Die Wahrscheinlichkeit, in einen bestimmten Behandlungsarm zugeteilt zu werden, beträgt 33%. Sie erhalten entweder die Behandlung mit Ibrutinib, mit Venetoclax und Obinutuzumab oder mit Ibrutinib und Venetoclax.

Health conditions investigated(Data source: BASEC)

Chronische lymphatische Leukämie

Health conditions (Data source: WHO)

Chronic Lymphoid Leukemia

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

I-Arm (Ibrutinib): In diesem Behandlungsarm erhalten Sie Ibrutinib über eine Behandlungsdauer von bis zu 7 Jahren. Die Behandlung wird erst beendet, wenn Nebenwirkungen aufgetreten sind, ein Fortschreiten der Erkrankung stattfand oder wenn die Studie zu Ende ist. Ggf. kann die Therapie nach Studienende von der Krankenkasse übernommen und weitergeführt werden. Dies bei Patienten, die bis zum Studienende von der Ibrutinib-Therapie profitieren, die weder Nebenwirkungen noch ein Fortschreiten der Erkrankung aufweisen.

VG-Arm (Venetoclax plus Obinutuzumab)
In diesem Behandlungsarm erhalten Sie Venetoclax für 12 Zyklen mit einer Dauer von 28 Tagen pro Zyklus, also ungefähr 12 Monate. Zusätzlich erhalten Sie in den ersten 6 Zyklen insgesamt 8 Infusionen mit dem Antikörper Obinutuzumab: Im ersten Zyklus dreimal im Abstand von 7 Tagen und dann im Abstand von 28 Tagen.

IV-Arm (Ibrutinib plus Venetoclax)
In diesem Behandlungsarm erhalten Sie Ibrutinib und Venetoclax für insgesamt 15 Zyklen mit einer Dauer von 28 Tagen pro Zyklus, also ungefähr 15 Monate. In den ersten drei Zyklen erhalten Sie zunächst nur Ibrutinib und ab Zyklus 4 beginnt die zusätzliche Einnahme von Venetoclax.

Interventions (Data source: WHO)

Biological: Ibrutinib;Biological: Venetoclax;Biological: Obinutuzumab

Criteria for participation in trial (Data source: BASEC)

- Dokumentierte Chronische lymphatische Leukämie
- Mindestalter 18 Jahre
- Lebenserartung von mehr als 6 Monaten

Exclusion criteria (Data source: BASEC)

- Es dürfen keine weiteren schweren Erkrankungen vorl iegen.
- Es darf keine gleichzeitige Einnahme von bestimmten Medikamenten oder Medikamenten in anderen klinischen Prüfungen erfolgen.
- Ebenfalls von einer Studienteilnahme ausgeschlossen sind schwangere und stillende Frauen.

Inclusion/Exclusion Criteria (Data source: WHO)

Gender: All
Maximum age: N/A
Minimum age: 18 Years

Inclusion Criteria:

1. Documented CLL requiring treatment according to iwCLL criteria.

2. Age at least 18 years.

3. Life expectancy = 6 months.

4. Ability and willingness to provide written informed consent and to adhere to the study
visit schedule and other protocol requirements.

5. Adequate bone marrow function independent of growth factor or transfusion support
within 2 weeks of screening initiation as follows, unless cytopenia is due to CLL:

1. Absolute neutrophil count = 1.0 ? 109/L

2. Platelet counts = 30 ? 109/L; in cases of thrombocytopenia clearly due to CLL
(per the discretion of the investigator), platelet count should be = 10 ? 109/L

3. Total haemoglobin = 9 g/dL (without transfusion support, unless anaemia is due to
CLL)

6. GFR >30ml/min directly measured with 24hr urine collection, calculated according to
the modified formula of Cockcroft and Gault (for men: GFR ? ((140 - age) x
bodyweight)/ (72 x creatinine), for women x 0, 85) or an equally accurate method.

a. For patients with creatinine values within the normal range the calculation of the
clearance is not necessary. Dehydrated patients with an estimated creatinine clearance
less than 30 ml/min may be eligible if a repeat estimate after adequate hydration is >
30 ml/min.

7. Adequate liver function as indicated by a total bilirubin = 2 x, AST/ ALT = 2.5 x the
institutional ULN value, unless directly attributable to the patient's CLL or to
Gilbert's Syndrome.

8. Negative serological testing for hepatitis B (HbsAg negative and anti-HBc negative;
patients positive for anti-HBc may be included if PCR for HBV DNA is negative and
HBV-DNA PCR is performed every month until 12 months after last treatment cycle),
negative testing for hepatitis C RNA within 6 weeks prior to registration for study
screening (i.e. PCR only required when serology was positive).

9. Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2.

Exclusion criteria:

1. Any prior CLL-specific therapies (except corticosteroid treatment administered due to
necessary immediate intervention; within the last 10 days before start of study
treatment, only dose equivalents up to 20 mg prednisolone are permitted).

2. Transformation of CLL (Richter transformation). When Richter transformation is
suspected, PET-CT and/or biopsy should be performed to rule out transformation.

3. Patients with a history of PML.

4. An individual organ/ system impairment score of 4 as assessed by the CIRS definition
limiting the ability to receive the study treatment 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).

5. Malignancies other than CLL currently requiring systemic therapies, not being treated
with curative intent before (unless the malignant disease is in a stable remission due
to the discretion of the treating physician or showing signs of progression after
curative treatment.

6. Uncontrolled or active infection.

7. Patients with known infection with human immunodeficiency virus (HIV).

8. Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/ inducers (incl. up to
7 days prior to study treatment start).

9. Anticoagulant therapy with warfarin or phenprocoumon, (alternative anticoagulation is
allowed (e.g. DOACs), but patients must be properly informed about the potential risk
of bleeding under treatment with ibrutinib).

10. History of stroke or intracranial hemorrhage within 6 months prior to registration for
study screening.

11. Known bleeding disorders

12. Child B / C liver cirrhosis

13. Use of investigational agents which might interfere with the study drug within 28 days
prior to registration for study screening.

14. Vaccination with live vaccines 28 days prior to registration for study screening.

15. Major surgery less than 30 days before start of study treatment.

16. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
antibodies, known sensitivity or allergy to murine products.

17. Known hypersensitivity to any active substance or to any of the excipients of one of
the drugs used in the trial.

18. Pregnant women and nursing mothers (a negative pregnancy test is required for all
women of childbearing potential within 7 days before start of study treatment; further
pregnancy testing will be performed monthly).

19. Fertile men or women of childbearing potential unless:

1. surgically sterile or = 2 years after the onset of menopause

2. willing to use two methods of reliable contraception including one highly
effective contraceptive method (Pearl Index <1) and one additional effective
(barrier) method during study treatment and for 18 months after the end of study
treatment.

20. Legal incapacity.

21. Prisoners or subjects who are institutionalized by regulatory or court order.

22. Persons who are in dependence to the sponsor or an investigator.

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/ct2/show/NCT04608318

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04608318
Further information on trial

Date trial registered

Oct 23, 2020

Recruitment status

Active, not recruiting

Academic title (Data source: WHO)

A Phase 3 Multicentre, Randomized, Prospective, Open-label Trial of Ibrutinib Monotherapy Versus Fixed-duration Venetoclax Plus Obinutuzumab Versus Fixed-duration Ibrutinib Plus Venetoclax in Patients With Previously Untreated Chronic Lymphocytic Leukaemia (CLL)

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 3

Primary end point (Data source: WHO)

Investigator-assessed progression-free survival (PFS)

Secundary end point (Data source: WHO)

Rates of undetectable minimal residual disease (uMRD) in peripheral blood (PB) and bone marrow (BM);MRD levels in PB at different time points;Overall response rate (ORR);CR/CRi rate;Incidence of safety parameters such as adverse events (AE) and adverse events of particular/special interest (AEPI/AESI)

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Aarau, Baden, Basel, Bellinzona, Bern, Brig, Brugg, Chur, Frauenfeld, Freiburg, Grabs, Liestal, Locarno, Lugano, Luzern, Mendrisio, Münsterlingen, St. Gallen, Thun, Uznach, Wil, Winterthur, Zurich

Countries (Data source: WHO)

Austria, Belgium, Denmark, Finland, Germany, Ireland, Israel, Italy, Netherlands, Norway, Spain, Sweden, Switzerland

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Julia Decoudre, SAKK
+41 31 389 91 91
trials@sakk.ch

Contact for general information (Data source: WHO)

Othman Al-Sawaf, Dr. med.
German CLL Study Group

Contact for scientific information (Data source: WHO)

Othman Al-Sawaf, Dr. med.
German CLL Study Group

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Ethikkommission Nordwest- und Zentralschweiz EKNZ

Date of authorisation by the ethics committee

30.11.2021

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2021-01861

Secondary ID (Data source: WHO)

2019-003854-99
CLL17
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