Einleitung wieder einblenden
EUCTR2016-003579-22 | SNCTP000002803

Untersuchung der Sicherheit und Wirksamkeit von Atezolizumab (TECENTRIQ®) in Kombination mit Obinutuzumab (GAZYVARO®) oder Rituximab (MabThera®) bei Patienten mit rezidivierendem/refraktärem Mantelzelllymphom, Marginalzonenlymphom oder Makroglobulinämie Waldenström.

Datenbasis: BASEC (Import vom 16.08.2019), WHO (Import vom 04.08.2019)
Geändert: 29.07.2019
Krankheitskategorie: Non-Hodgkin-Lymphom

Zusammenfassende Beschreibung der Studie (Datenquelle: BASEC)

Es handelt sich um eine internationale Studie, die in mehreren Ländern durchgeführt wird. Weltweit werden ungefähr 120 Patienten an dieser Studie teilnehmen. Patienten die sich für die Teilnahme an dieser Studie eignen erhalten die Prüfpräparate Atezolizumab plus Obinutuzumab oder Atezolizumab plus Rituximab. Das Ziel der Studie ist die Untersuchung der Sicherheit und Wirksamkeit von Atezolizumab bei Anwendung in Kombination mit Obinutuzumab oder Rituximab bei Patienten mit rezidivierendem oder refraktärem Mantelzelllymphom, Marginalzonenlymphom oder Makroglobulinämie Waldenström.

Untersuchte Krankheiten (Datenquelle: BASEC)

Untersucht werden das rezidivierende/refraktäre Mantelzelllymphom, Marginalzonenlymphom oder Makroglobulinämie Waldenström.

Health conditions (Datenquelle: WHO)

Relapsed/Refractory Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL) and Waldenström Macroglobulinemia (WM)
MedDRA version: 20.1Level: LLTClassification code 10054697Term: Waldenstrom's macroglobulinemia recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.1Level: LLTClassification code 10054698Term: Waldenstrom's macroglobulinemia refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: PTClassification code 10077534Term: Marginal zone lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: PTClassification code 10077533Term: Marginal zone lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: PTClassification code 10026801Term: Mantle cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: PTClassification code 10026800Term: Mantle cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Seltene Krankheit (Datenquelle: BASEC)

Nein

Untersuchte Intervention (z.B. Medikament, Therapie, Kampagne) (Datenquelle: BASEC)

Teilnehmende mit Marginalzonenlymphom erhalten in den ersten 8 Zyklen (ein Zyklus beträgt 3 Wochen) Atezolizumab und Rituximab. Dies wird als Einleitungsphase bezeichnet.
Im ersten Zyklus wird Rituximab über eine Armvene (intravenöse Infusion) direkt in den Blutkreislauf gegeben. Im zweiten bis achten Zyklus wird Rituximab als Spritze unter die Haut gegeben (subkutan). Atezolizumab wird vom ersten bis zum achten Zyklus alle 3 Wochen über eine Armvene direkt in den Blutkreislauf gegeben.
Teilnehmende mit Mantelzelllymphom oder Waldenström erhalten in den ersten 8 Zyklen (Einleitungsphase) Atezolizumab und Obinutzumab. Obinutuzumab wird an Tag 1, 8 und 15 des 1. Zyklus über eine Armvene (intravenöse Infusion) direkt in den Blutkreislauf verabreicht. Im 2. bis 8. Zyklus wird Obinutzumab alle 3 Wochen gegeben.
Atezolizumab vom 1. bis zum 8. Zyklus alle 3 Wochen, intravenös verabreicht.
In der Erhaltungsphase erhalten alle Teilnehmenden ab Zyklus 9 bis 18 nur Atezolizumab alle 3 Wochen intravenös.
Wenn die Behandlung mit Atezolizumab während der Erhaltungsphase (d. h. in Zyklus 9 bis 18) beendet werden muss, geht der Teilnehmende von der einfachen Studienbehandlung zur Nachbeobachtungs-Phase der Studie über.

Interventions (Datenquelle: WHO)


Product Name: Atezolizumab
Product Code: RO5541267
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
CAS Number: 1380723-44
Current Sponsor code: RO5541267
Other descriptive name: TECENTRIQ
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Trade Name: Gazyvaro 1,000 mg
Pharmaceutical Form:
INN or Proposed INN: Obinutuzumab
CAS Number: 949142-50-1
Current Sponsor code: RO5072759
Other descriptive name: OBINUTUZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-

Trade Name: MabThera 500 mg concentrate for solution for infusion
Product Name: MabThera 500 mg concentrate for solution for infusion
Product Code: RO0452294
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Current Sponsor code: RO452294
Other descriptive name: MabThera 500 mg concentrate for solution for infusion
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: MabThera 1400 mg solution for subcutaneous injection
Product Name: MabThera 1400 mg solution for subcutaneous injection
Product Code: RO0452294
Pharmaceutical Form: Solution for injection
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Other descriptive name: MabThera 1400 mg solution for subcutaneous injection
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-

Trade Name: Tecentriq
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Kriterien zur Teilnahme an der Studie (Datenquelle: BASEC)

- Teilnehmer mit histologisch dokumentiertem CD20-positivem Non-Hodgkin Lymphom
- Biopsie des Knochenmarks und/oder anderer erkrankter Stellen zum Zeitpunkt der Voruntersuchung
- Teilnehmer mit Mantelzelllymphom und nodalem Marginalzonenlymphom eine messbare Läsion im Computertomographie oder Magnetresonanztomographie haben
- Tumorgewebe (vorzugsweise eine frische Probe) oder archiviertes Gewebe (nur wenn keine frische Probe verfügbar ist)
- Männer während der Studienteilnahme verhüten

Ausschlusskriterien (Datenquelle: BASEC)

- Behandlung mit einer Krebstherapie (einschliesslich Chemotherapie) oder Hormontherapie innerhalb von 3 Wochen vor Beginn der Studienbehandlung oder Behandlung mit einer Strahlentherapie innerhalb von 4 Wochen vor Beginn der Studienbehandlung.
- Behandlung mit anderen Prüfpräparaten oder Teilnahme an einer anderen therapeutischen klinischen Studie innerhalb von 28 Tagen vor Studieneinschluss.
- Anzeichen einer signifikanten unkontrollierten Begleiterkrankung, die die Einhaltung des Protokolls beeinträchtigen könnte
- Frauen im gebärfähigen Alter dürfen nicht schwanger sein oder werden.

Inclusion/Exclusion Criteria (Datenquelle: WHO)

Inclusion criteria:
- Ability to comply with the protocol
- Age >= 18 years
- Histologically documented, CD20 positive, relapsed or refractory MCL, MZL and WM. Refractory is defined for the 3 indications as having relapsed during or within 6 months after the last dose of the previous treatment. . For WM patients, the diagnosis of relapse/refractory will be accompanied by evidence of reappearance of monoclonal IgM protein and/or recurrence of bone marrow involvement, lymphadenopathy/splenomegaly with symptoms attributable to active disease Where ibrutinib is available in the selected country, patients with MCL or WM must have relapsed or become refractory to its benefits, or become intolerant of ibrutinib. All other patients must have failed at least 1 prior line of systemic treatment.
- Bone marrow biopsy and/or other sites of disease at screening for tumor staging and response evaluation
- ECOG performance status of 0, 1 or 2
- Life expectancy>=12 weeks
- For mantle cell lymphoma (MCL) and nodal marginal zone lymphoma (MZL), at least one bi-dimensionally measurable lesion>=1.5 cm in its largest dimension by Computed Tomography scan or MRI, as defined by Revised Response Criteria for Malignant Lymphoma
- Adequate hematologic and end-organ function
- For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or to use single highly effective or combined contraceptive methods that result in a failure rate of < 1% per year, starting at least 28 days prior to Day 1 of Cycle 1, during the treatment period for at least 18 months after the last dose of combination therapy
- For women of childbearing potential (including premenopausal women who have had tubal ligation and women not meeting the definition of postmenopausal), a negative serum pregnancy test result on Day 1 of Cycle 1 prior to dosing. For all other women, documentation must be present in the medical history confirming that the patient is not of childbearing potential.
- For men, agreement to remain abstinent or to use a condom plus an additional contraceptive method that together result in a failure rate of 1% per year during the treatment period and for at least 3 months after the last dose of combination therapy
- Tumor tissue fresh sample preferred, archival tissue is acceptable (only if a fresh sample is not available).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 84

Exclusion criteria:
- Any approved anticancer therapy or hormonal therapy within 3 weeks prior to initiation of study treatment. Any radiotherapy within 4 weeks prior to initiation of study treatment.
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or 5 half-lifes prior to enrolment, whichever is longest.
- Known Central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of transformation to a high-grade or diffuse large B-cell lymphoma
- Uncontrolled tumor-related pain
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures

Weitere Angaben zur Studie im WHO-Primärregister

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003579-22

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2016-003579-22-LV

Weitere Informationen zur Studie

Registrationsdatum der Studie

16.06.2017

Einschluss der ersten teilnehmenden Person

30.08.2017

Rekrutierungsstatus

Authorised-recruitment may be ongoing or finished

Wissenschaftlicher Titel (Datenquelle: WHO)

A PHASE II STUDY EXPLORING THE SAFETY AND EFFICACY OF ATEZOLIZUMAB ADMINISTERED IN COMBINATION WITH OBINUTUZUMAB OR RITUXIMAB ANTI-CD20 THERAPY IN PATIENTS WITH RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA, MARGINAL ZONE LYMPHOMA AND WALDENSTRÖM MACROGLOBULINEMIA

Studientyp (Datenquelle: WHO)

Interventional clinical trial of medicinal product

Design der Studie (Datenquelle: WHO)

Controlled: noRandomised: noOpen: yesSingle blind: noDouble blind: noParallel group: noCross over: noOther: noIf controlled, specify comparator, Other Medicinial Product: noPlacebo: noOther: noNumber of treatment arms in the trial: 3

Phase (Datenquelle: WHO)

Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): yesTherapeutic confirmatory - (Phase III): noTherapeutic use (Phase IV): no

Primäre Endpunkte (Datenquelle: WHO)

Main Objective: To evaluate the efficacy of atezolizumab in combination with obinutuzumab or rituximab;Secondary Objective: • To evaluate the efficacy of atezolizumab in combination with obinutuzumab or rituximab
• To evaluate the safety and tolerability of atezolizumab in combination with obinutuzumab or rituximab
• To characterize the pharmacokinetics of atezolizumab and obinutuzumab when administered in combination in MCL and WM patients
• To characterize the pharmacokinetics of atezolizumab and rituximab when administered in combination in MZL patients
• To evaluate the immune response to atezolizumab with obinutuzumab or rituximab
;Primary end point(s): 1. For MCL and nodal and extra-nodal MZL, objective response (OR) at end of Induction, defined as a complete response (CR) or partial response (PR) based on modified Cheson 2007 criteria (excluding PET)
2. For WM, best overall objective response (BOR), defined as a CR, very good partial response, PR, or minimum response, based on Owen 2013 criteria
3. For gastric MZL, OR at end of Induction, defined as a CR or probable minimal residual disease or responding residual disease, based on the histological grading system of GELA 2003 criteria
4. For splenic MZL, OR at end of Induction, defined as a CR or PR based on Matutes (2008)

Sekundäre Endpunkte (Datenquelle: WHO)

Secondary end point(s): 1. Progression-free survival (PFS), defined as the time from enrolment to the first occurrence of PD or death, as determined by the investigator
2. BOR, defined as best response seen throughout study
3. Complete Response Rate defined as best response of CR
4. Duration of objective response, defined for responding patients as the first occurrence of a documented objective response to the time of progression or death from any cause, whichever occurs first
5. Time to next treatment, defined as the time from the date of enrolment to the start date of the next anti-lymphoma treatment (NALT) or death from any cause
6. Overall survival, defined as the time from the enrolment to death from any cause
7. Event free survival, defined as the time from enrolment to disease progression or relapse, death from any cause, as assessed by the investigator, or initiation of any NALT, whichever occurs first.
8. Disease-free survival, defined as the time from the date of the first occurrence of a documented CR to the date of disease progression, relapse or death from any cause (PFS), as assessed by the investigator, for the subgroup of patients with a BOR of CR
9. Response rates for MCL and nodal/extranodal MZL using the assessment based on FDG-PET scans based on modified Cheson 2007
10. Safety: Incidence, nature and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03)
11. Pharmacokinetic parameters of atezolizumab, obinutuzumab, and rituximab
12. Occurrence of anti-drug antibodies of atezolizumab, obinutuzumab, and rituximab;Timepoint(s) of evaluation of this end point: 1-10. Up to approximately 54 months
11. C1D1, C2D1, C3D1, C4D1, C8D1, C12D1, C16D1 (atezolizumab); C1D1, C2D1, C4D1 (obinutuzumab); C1D1, C2D1, C4D1, C8D1 (rituximab), end of treatment (EOT) and at Follow-up 1 (FU1)
12. C1D1, C2D1, C34D1, C4D1, C8D1, C12D1, C16D1 (atezolizumab); C1D1, C4D1 (obinutuzumab); C1D1, C4D1 (rituximab)

Kontakt für Auskünfte (Datenquelle: WHO)

F.Hoffman-La Roche Ltd.

Studiendurchführungsorte

Durchführungsorte in der Schweiz (Datenquelle: BASEC)

Bellinzona, Genf, Zürich

Durchführungsländer (Datenquelle: WHO)

Bosnia and Herzegovina, France, Germany, Greece, Korea, Latvia, Republic of, Russian Federation, Slovakia, Spain, Switzerland

Kontakt für weitere Auskünfte zur Studie

Angaben zur Kontaktperson in der Schweiz (Datenquelle: BASEC)

Ellen van Vijnckt
+ 41 61 715 43 74
switzerland.clinical-research@roche.com

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

Trial Information Support Line-TISL
Grenzacherstrasse 124
F.Hoffmann-La Roche Ltd.
global.rochegenentechtrials@roche.com

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Trial Information Support Line-TISL
Grenzacherstrasse 124
F.Hoffmann-La Roche Ltd.
global.rochegenentechtrials@roche.com

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

F. Hoffmann-La Roche Ltd

Weitere Studienidentifikationsnummern

BASEC ID (Datenquelle: BASEC)

2017-01560

Secondary ID (Datenquelle: WHO)

MO39107