A Study to Compare Subcutaneous Versus Intravenous MabThera (Rituximab) in Combination With Chemotherapy in Patients With Chronic Lymphocytic Leukemia

NCT ID: NCT01292603

Last Updated: 2018-12-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-04-18

Study Completion Date

2017-11-17

Brief Summary

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This randomized, parallel-group, multi-center study will compare the pharmacokinetics and safety of subcutaneous administration of MabThera (rituximab) versus intravenous MabThera in combination with chemotherapy in previously untreated patients with chronic lymphocytic leukemia (CLL). The study consists of 2 parts. In part 1, patients who have previously received 4 cycles of intravenous MabThera will receive in Cycle 5 intravenous MabThera and in Cycle 6 subcutaneous MabThera. In part 2, patients will be randomized to receive either 6 cycles of intravenous MabThera, or 1 cycle of intravenous MabThera and 5 cycles of subcutaneous MabThera. Additionally, all patients will receive chemotherapy (fludarabine and cyclophosphamide) on Days 1-3 or Days 1-5 of every cycle. The anticipated time on study drug is 24 weeks.

Detailed Description

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Conditions

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Lymphocytic Leukemia, Chronic

Study Design

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Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Days 1-3 or Days 1-5 of cycles 1-6

Fludarabine

Intervention Type DRUG

Days 1-3 or Days 1-5 of cycles 1-6

rituximab [MabThera]

Intervention Type DRUG

After 4 cycles of intravenous MabThera without experiencing grade 3 or 4 infusion-related reactions. patients will receive 1 additional cycle of intravenous MabThera and 1 cycle of subcutaneous MabThera.

2

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Days 1-3 or Days 1-5 of cycles 1-6

Fludarabine

Intervention Type DRUG

Days 1-3 or Days 1-5 of cycles 1-6

rituximab [MabThera]

Intervention Type DRUG

6 cycles of intravenous MabThera

3

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Days 1-3 or Days 1-5 of cycles 1-6

Fludarabine

Intervention Type DRUG

Days 1-3 or Days 1-5 of cycles 1-6

rituximab [MabThera]

Intervention Type DRUG

One cycle of intravenous MabThera, followed by 5 cycles of subcutaneous MabThera

Interventions

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Cyclophosphamide

Days 1-3 or Days 1-5 of cycles 1-6

Intervention Type DRUG

Fludarabine

Days 1-3 or Days 1-5 of cycles 1-6

Intervention Type DRUG

rituximab [MabThera]

One cycle of intravenous MabThera, followed by 5 cycles of subcutaneous MabThera

Intervention Type DRUG

rituximab [MabThera]

After 4 cycles of intravenous MabThera without experiencing grade 3 or 4 infusion-related reactions. patients will receive 1 additional cycle of intravenous MabThera and 1 cycle of subcutaneous MabThera.

Intervention Type DRUG

rituximab [MabThera]

6 cycles of intravenous MabThera

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Adult patients, \>/=18 years of age
* Patients with treatment-requiring chronic lymphocytic leukemia (CLL)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Life expectancy \>6 months

Exclusion Criteria

* Transformation to aggressive B-cell malignancy
* History of other malignancy unless the patient was treated with curative intent and has been in remission for more than 5 years prior to enrolment
* HIV or Hepatitis B positive unless clearly due to vaccination
* Inadequate liver or renal function
* Any coexisting medical or psychological condition that would preclude participation in the required study procedures

Additional exclusion criterion for Part 1:

* Any previous treatment for CLL except for up to 4 cycles of rituximab IV in combination with FC chemotherapy as first-line treatment for CLL

Additional exclusion criterion for Part 2:

* Any previous treatment for CLL
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Fundaleu; Haematology

Buenos Aires, , Argentina

Site Status

Cemic; Haematology

Buenos Aires, , Argentina

Site Status

HOSPITAL PRIVADO - CENTRO MEDICO DE CÓRDOBA; Dpto Oncología

Córdoba, , Argentina

Site Status

St George Hospital; Department of Haematology

Kogarah, New South Wales, Australia

Site Status

Royal Brisbane and Women'S Hospital; Haematology

Herston, Queensland, Australia

Site Status

Ashford Cancer Center Research

Kurralta Park, South Australia, Australia

Site Status

Queen Elizabeth Hospital; Haematology

Woodville South, South Australia, Australia

Site Status

St Vincent'S Hospital; Haematology

Fitzroy, Victoria, Australia

Site Status

Frankston Hospital; Oncology/Haematology

Frankston, Victoria, Australia

Site Status

Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia

Passo Fundo, Rio Grande do Sul, Brazil

Site Status

Hospital Mae de Deus

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital Sirio Libanes; Centro de Oncologia

São Paulo, São Paulo, Brazil

Site Status

Hospital das Clinicas - FMUSP

São Paulo, São Paulo, Brazil

Site Status

Queen Elizabeth II Health Sciences Centre; Oncology

Halifax, Nova Scotia, Canada

Site Status

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

Montreal, Quebec, Canada

Site Status

Centre de sante et de services sociaux Rimouski Neigette

Rimouski, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Site Status

Instituto Nacional del Cancer

Santiago, , Chile

Site Status

Centro Internacional de Estudios Clínicos (CIEC)

Santiago, , Chile

Site Status

Clinical Hospital Merkur; Dept of Haematology

Zagreb, , Croatia

Site Status

University Hospital Center Zagreb; Haematology Department

Zagreb, , Croatia

Site Status

Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika

Brno, , Czechia

Site Status

University Hospital and Medical School; IV.Dept. of Internal Medicine and Hematology

Hradec Králové, , Czechia

Site Status

Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK

Prague, , Czechia

Site Status

Centre Francois Baclesse

Caen, , France

Site Status

Institut J Paolii Calmettes; Onco Hematologie 1

Marseille, , France

Site Status

Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)

Paris, , France

Site Status

Hopital Robert Debre; Hematologie Clinique

Reims, , France

Site Status

Hopitaux De Brabois; Hematologie Medecine Interne

Vandœuvre-lès-Nancy, , France

Site Status

Onkologische Schwerpunktpraxis Kurfürstendamm

Berlin, , Germany

Site Status

Onkologischer Schwerpunkt am Oskar-Helene-Heim; Dres. Herrenberger, Keitel-Wittig u. Kirsch

Berlin, , Germany

Site Status

Klinik der Uni zu Köln; Klinik für Innere Medizin

Cologne, , Germany

Site Status

BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie

Dresden, , Germany

Site Status

Klinikum Frankfurt; Medizinische Klinik I

Frankfurt (Oder), , Germany

Site Status

Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik

Greifswald, , Germany

Site Status

Onkologische Schwerpunktpraxis Dres. Bernd Gaede, Hans-Ulrich Ehlers, Ulrike Rodewig u.w.

Hanover, , Germany

Site Status

Gemeinschaftspraxis Dr. Siehl & Dr. Soeling

Kassel, , Germany

Site Status

K&K Studien GbR

Landshut, , Germany

Site Status

Onkologische Schwerpunktpraxis Lübeck

Lübeck, , Germany

Site Status

Gemeinschaftspraxis Fr. Dr. med. Balser & Hr. Dr. med. Weidenbach

Marburg, , Germany

Site Status

Medizinisches Versorgungszentrum MOP

München, , Germany

Site Status

Klinikum Grosshadern der LMU

München, , Germany

Site Status

Gemeinschaftspraxis Dr. med. Holger Klaproth / Dr. med. Anca Astrid Cura

Neunkirchen/Saar, , Germany

Site Status

Prosper-Hospital, Medizinische Klinik I

Recklinghausen, , Germany

Site Status

Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine

Athens, , Greece

Site Status

Papageorgiou General Hospital of Thessaloniki; Hematology Clinic

Thessaloniki, , Greece

Site Status

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

Meldola, Emilia-Romagna, Italy

Site Status

Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia

Ravenna, Emilia-Romagna, Italy

Site Status

Ospedale Infermi Di Rimini; Unità Operativa di Oncologia e Oncoematologia

Rimini, Emilia-Romagna, Italy

Site Status

A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Ematologica

Udine, Friuli Venezia Giulia, Italy

Site Status

Istituto S. Raffaele Monte Tabor; Divisione Ematologia E Utmo

Milan, Lombardy, Italy

Site Status

ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Struttura Complessa di Ematologia

Milan, Lombardy, Italy

Site Status

Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad

Novara, Piedmont, Italy

Site Status

Policlinico G. B. Rossi; Divisione Di Ematologia

Verona, Veneto, Italy

Site Status

Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre

Chihuahua City, , Mexico

Site Status

Hospital General De Culiacan; Servicio De Hematologia

Culiacán, , Mexico

Site Status

Hospital Universitario Dr. Jose E. Gonzalez; Haematology

Monterrey, , Mexico

Site Status

Canterbury Health Laboratories; Haematology

Christchurch, , New Zealand

Site Status

Wellington Hospital; Wellington Blood and Cancer Centre

Newtown, , New Zealand

Site Status

Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii

Gdansk, , Poland

Site Status

Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie

Lublin, , Poland

Site Status

Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Lymphoma Dept.

Warsaw, , Poland

Site Status

Medical Uni of Wroclaw; Hematology

Wroclaw, , Poland

Site Status

Hospital de Santa Maria; Servico de Hematologia e Transplantacao de Medula

Lisbon, , Portugal

Site Status

IPO do Porto; Servico de Onco-Hematologia

Porto, , Portugal

Site Status

N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis

Moscow, , Russia

Site Status

City Clinical Hospital After Botkin; Hematology

Moscow, , Russia

Site Status

Haematology Research Center; Haematology

Moscow, , Russia

Site Status

Penza Regional Oncology Dispensary

Penza, , Russia

Site Status

Clinical MSCh No1

Perm, , Russia

Site Status

St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta

Saint Petersburg, , Russia

Site Status

National Oncology Inst. ; Dept. of Haematology

Bratislava, , Slovakia

Site Status

University Hospital; Clinic of Hematology & Transfusiology

Bratislava, , Slovakia

Site Status

Hospital Universitari Vall d'Hebron; Servicio de Hematologia

Barcelona, , Spain

Site Status

Hospital Universitario de la Princesa; Servicio de Hematologia

Madrid, , Spain

Site Status

Hospital Universitario Puerta de Hierro; Servicio de Hematologia

Madrid, , Spain

Site Status

Hospital Clinico Universitario de Salamanca;Servicio de Hematologia

Salamanca, , Spain

Site Status

Hospital Universitario Virgen del Rocio; Servicio de Hematologia

Seville, , Spain

Site Status

Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Hematología

Toledo, , Spain

Site Status

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, , Spain

Site Status

Hacettepe Uni Medical Faculty; Hematology

Ankara, , Turkey (Türkiye)

Site Status

Istanbul University Cerrahpasa Medical Faculty; Hematology Department

Istanbul, , Turkey (Türkiye)

Site Status

Dokuz Eylul Uni ; Hematology

Izmir, , Turkey (Türkiye)

Site Status

Ege University ARGEFAR

Izmir, , Turkey (Türkiye)

Site Status

Countries

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Argentina Australia Brazil Canada Chile Croatia Czechia France Germany Greece Italy Mexico New Zealand Poland Portugal Russia Slovakia Spain Turkey (Türkiye)

References

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Assouline S, Buccheri V, Delmer A, Gaidano G, Trneny M, Berthillon N, Brewster M, Catalani O, Li S, McIntyre C, Sayyed P, Badoux X. Pharmacokinetics, safety, and efficacy of subcutaneous versus intravenous rituximab plus chemotherapy as treatment for chronic lymphocytic leukaemia (SAWYER): a phase 1b, open-label, randomised controlled non-inferiority trial. Lancet Haematol. 2016 Mar;3(3):e128-38. doi: 10.1016/S2352-3026(16)00004-1.

Reference Type DERIVED
PMID: 26947201 (View on PubMed)

Assouline S, Buccheri V, Delmer A, Gaidano G, McIntyre C, Brewster M, Catalani O, Hourcade-Potelleret F, Sayyed P, Badoux X. Pharmacokinetics and safety of subcutaneous rituximab plus fludarabine and cyclophosphamide for patients with chronic lymphocytic leukaemia. Br J Clin Pharmacol. 2015 Nov;80(5):1001-9. doi: 10.1111/bcp.12662. Epub 2015 Jul 29.

Reference Type DERIVED
PMID: 25900065 (View on PubMed)

Mao CP, Brovarney MR, Dabbagh K, Birnbock HF, Richter WF, Del Nagro CJ. Subcutaneous versus intravenous administration of rituximab: pharmacokinetics, CD20 target coverage and B-cell depletion in cynomolgus monkeys. PLoS One. 2013 Nov 12;8(11):e80533. doi: 10.1371/journal.pone.0080533. eCollection 2013.

Reference Type DERIVED
PMID: 24265828 (View on PubMed)

Shpilberg O, Jackisch C. Subcutaneous administration of rituximab (MabThera) and trastuzumab (Herceptin) using hyaluronidase. Br J Cancer. 2013 Sep 17;109(6):1556-61. doi: 10.1038/bjc.2013.371. Epub 2013 Sep 3.

Reference Type DERIVED
PMID: 24002601 (View on PubMed)

Other Identifiers

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2010-021380-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO25341

Identifier Type: -

Identifier Source: org_study_id