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

Primary Purpose

Lymphocytic Leukemia, Chronic

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Cyclophosphamide

Fludarabine

rituximab [MabThera]

About this trial

This is an interventional treatment trial for Lymphocytic Leukemia, Chronic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Fundaleu; Haematology
Cemic; Haematology
HOSPITAL PRIVADO - CENTRO MEDICO DE CÓRDOBA; Dpto Oncología
St George Hospital; Department of Haematology
Royal Brisbane and Women'S Hospital; Haematology
Ashford Cancer Center Research
Queen Elizabeth Hospital; Haematology
St Vincent'S Hospital; Haematology
Frankston Hospital; Oncology/Haematology
Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia
Hospital Mae de Deus
Hospital Sirio Libanes; Centro de Oncologia
Hospital das Clinicas - FMUSP
Queen Elizabeth II Health Sciences Centre; Oncology
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
Centre de sante et de services sociaux Rimouski Neigette
Centre Hospitalier Universitaire de Sherbrooke
Instituto Nacional del Cancer
Centro Internacional de Estudios Clínicos (CIEC)
Clinical Hospital Merkur; Dept of Haematology
University Hospital Center Zagreb; Haematology Department
Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
University Hospital and Medical School; IV.Dept. of Internal Medicine and Hematology
Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK
Centre Francois Baclesse
Institut J Paolii Calmettes; Onco Hematologie 1
Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)
Hopital Robert Debre; Hematologie Clinique
Hopitaux De Brabois; Hematologie Medecine Interne
Onkologische Schwerpunktpraxis Kurfürstendamm
Onkologischer Schwerpunkt am Oskar-Helene-Heim; Dres. Herrenberger, Keitel-Wittig u. Kirsch
BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie
Klinikum Frankfurt; Medizinische Klinik I
Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik
Onkologische Schwerpunktpraxis Dres. Bernd Gaede, Hans-Ulrich Ehlers, Ulrike Rodewig u.w.
Gemeinschaftspraxis Dr. Siehl & Dr. Soeling
Klinik der Uni zu Köln; Klinik für Innere Medizin
K&K Studien GbR
Onkologische Schwerpunktpraxis Lübeck
Gemeinschaftspraxis Fr. Dr. med. Balser & Hr. Dr. med. Weidenbach
Klinikum Grosshadern der LMU
Medizinisches Versorgungszentrum MOP
Gemeinschaftspraxis Dr. med. Holger Klaproth / Dr. med. Anca Astrid Cura
Prosper-Hospital, Medizinische Klinik I
Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine
Papageorgiou General Hospital of Thessaloniki; Hematology Clinic
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia
Ospedale Infermi Di Rimini; Unità Operativa di Oncologia e Oncoematologia
A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Ematologica
Istituto S. Raffaele Monte Tabor; Divisione Ematologia E Utmo
ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Struttura Complessa di Ematologia
Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad
Policlinico G. B. Rossi; Divisione Di Ematologia
Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre
Hospital General De Culiacan; Servicio De Hematologia
Hospital Universitario Dr. Jose E. Gonzalez; Haematology
Canterbury Health Laboratories; Haematology
Wellington Hospital; Wellington Blood and Cancer Centre
Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii
Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie
Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Lymphoma Dept.
Medical Uni of Wroclaw; Hematology
Hospital de Santa Maria; Servico de Hematologia e Transplantacao de Medula
IPO do Porto; Servico de Onco-Hematologia
N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
City Clinical Hospital After Botkin; Hematology
Haematology Research Center; Haematology
Penza Regional Oncology Dispensary
Clinical MSCh No1
St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta
National Oncology Inst. ; Dept. of Haematology
University Hospital; Clinic of Hematology & Transfusiology
Hospital Universitari Vall d'Hebron; Servicio de Hematologia
Hospital Universitario de la Princesa; Servicio de Hematologia
Hospital Universitario Puerta de Hierro; Servicio de Hematologia
Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
Hospital Universitario Virgen del Rocio; Servicio de Hematologia
Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Hematología
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
Hacettepe Uni Medical Faculty; Hematology
Istanbul University Cerrahpasa Medical Faculty; Hematology Department
Dokuz Eylul Uni ; Hematology
Ege University ARGEFAR

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Arm Description

Outcomes

Primary Outcome Measures

Part 1: Subcutaneous Rituximab Dose Resulting in Trough Concentration (Ctrough) Levels Non-Inferior to Intravenous Rituximab

Ctrough is defined as the trough or minimum serum concentration. Pharmacokinetic parameters for rituximab were assessed during Cycles 5 (IV rituximab) and 6 (SC rituximab). Rituximab pharmacokinetic (PK) data from Part 1 were integrated into a population PK model using parametric, nonlinear, mixed-effects modelling. Rituximab IV 500 mg/m^2 administered once every 4 weeks was compared to fixed doses of rituximab SC between 1400 mg and 1870 mg. The dose selection was performed on Ctrough concentrations at Cycle 5 (pre-dose Cycle 6). A test of the probability of success was applied to each of the 100 replicates, and the percentage of replicates with a positive test corresponded to the probability of success of the trial.

Part 2: Rituximab C Trough Levels at Cycle 5

Ctrough is defined as the trough or minimum serum concentration in a given cycle of treatment. The objective of Part 2 was to demonstrate the comparability of the observed Ctrough of rituximab SC 1600 mg and rituximab IV 500 mg/m2 at Cycle 5, as assessed by a non-inferiority test with a lower boundary of at least 0.8 for the 90% CI.

Secondary Outcome Measures

Part 2: Observed Area Under the Serum Concentration-Curve (AUC) of Rituximab at Cycle 6

AUC values were calculated by numerical integration using the linear trapezoidal rule. AUC levels were analyzed using the model below: Ln(AUC) = μ + τi + BlTLij + εij wherein, Ln is the natural log, μ denotes the overall mean effect, τi the effect in each treatment group, BlTLij the tumor load at baseline for each patient and εij a random error variable with normal distribution and mean 0. The treatment effect therein was based on a contrast statement in the model to calculate 90 % confidence intervals for ln(AUC SC)- ln(AUC IV).

Part 2: Maximum Observed Concentration (Cmax) of Rituximab at Cycle 6

Cmax was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of rituximab in the blood samplings.

Part 2: Time to Cmax (Tmax) of Rituximab at Cycle 6

Multiple blood samples were obtained at pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6 in Rituximab IV arm, and at pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6 in Rituximab SC arm and time to peak plasma concentration of rituximab was determined.

Part 2: Terminal Half-Life of Rituximab at Cycle 6

The terminal half-life (t1/2) of rituximab is defined as the time required for the plasma concentration of rituximab to reach half of its original concentration.

Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration

In part 1 of the trial, upon completion of dosing in cycle 6, participants and their treating nurses were asked whether they have a preference of dosing route, IV vs SC

Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV

Physicians and nurses who administered rituximab were asked to answer the following question: " If used in routine practice, on average, how much staff time could be saved with each administration of rituximab SC as compared to rituximab IV? (Please do not consider the time needed for the first IV administration, consider only the subsequent ones)". The number of nurses that responded for both the IV and SC arms was 70. The number of physicians that responded for the IV and SC arms were 78 and 81 respectively.

Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV

Physicians and nurses who administered rituximab were asked to answer the following question: "Which formulation of rituximab (SC or IV) do you think is more convenient?" with pre-specified responses as below. Percentage of participants with specified answers were reported. The number of nurses that responded for both the IV and SC arms was 70. The number of physicians that responded for the IV and SC arms were 78 and 81 respectively.

Part 1: Percentage of Participants With Anti-Rituximab Antibodies

Blood samples for the assessment of antibodies against rituximab (HACAs) were drawn pre-dose at Cycle 5 and Cycle 6 in Part 1 and at each follow up visit until 24 months after the last dose.

Part 2: Percentage of Participants With Anti-Rituximab Antibodies

In Part 2, samples for the HACA assay were collected at each treatment cycle prior to the administration of rituximab and at each follow-up visit until 24 months after the last dose of rituximab.

Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit

CD 19 is a surface antigen (protein) present on B-lymphocytes.

Part 1: Percentage of Participants With Total B-Cell Depletion by Visit

Total B-cell depletion (normal B-cell plus Malignant B-cell depletion) was defined for each individual participant when the sum of CD5-/CD19+ (normal B-cells) and CD5+/CD19+ (malignant B-cells) cell counts decreased below 80 cells/μL.

Part 2: Total CD19+ B-Cell Counts by Visit

CD 19 is a surface antigen (protein) present on B-lymphocytes.

Part 2: Percentage of Participants With Total B-Cell Depletion by Visit

Full Information

NCT ID

NCT01292603

First Posted

February 8, 2011

Last Updated

November 17, 2018

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT01292603

Brief Title

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

Official Title

An Adaptive, Comparative, Randomized, Parallel-group, Multi Center, Phase Ib Study of Subcutaneous (SC) Rituximab Versus Intravenous (IV) Rituximab Both in Combination With Chemotherapy (Fludarabine and Cyclophosphamide), in Patients With Previously Untreated CLL

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Completed

Study Start Date

April 18, 2011 (Actual)

Primary Completion Date

May 7, 2014 (Actual)

Study Completion Date

November 17, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphocytic Leukemia, Chronic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Enrollment

240 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Title

Arm Type

Experimental

Arm Title

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

rituximab [MabThera]

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

rituximab [MabThera]

Intervention Description

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

Intervention Name(s)

rituximab [MabThera]

Intervention Description

6 cycles of intravenous MabThera

Primary Outcome Measure Information:

Title

Part 1: Subcutaneous Rituximab Dose Resulting in Trough Concentration (Ctrough) Levels Non-Inferior to Intravenous Rituximab

Description

Time Frame

Pre-dose and post-dose (15 minutes to end of infusion) on Day 1 and on Days 2, 5, 11 and 15 of Cycle 5 and Pre-dose, Post-dose on Days 2, 3, 5,11, 15 and 29 of Cycle 6; Pre-dose was taken 2 hours prior rituximab dose

Title

Part 2: Rituximab C Trough Levels at Cycle 5

Description

Time Frame

+/- 25hours around the 28th day post the 5th Cycle of Rituximab administration

Secondary Outcome Measure Information:

Title

Part 2: Observed Area Under the Serum Concentration-Curve (AUC) of Rituximab at Cycle 6

Description

Time Frame

Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6

Title

Part 2: Maximum Observed Concentration (Cmax) of Rituximab at Cycle 6

Description

Time Frame

Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6

Title

Part 2: Time to Cmax (Tmax) of Rituximab at Cycle 6

Description

Time Frame

Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6

Title

Part 2: Terminal Half-Life of Rituximab at Cycle 6

Description

The terminal half-life (t1/2) of rituximab is defined as the time required for the plasma concentration of rituximab to reach half of its original concentration.

Time Frame

Rituximab IV arm: pre-dose, post-dose and on Days 2, 3, 8 ,15, 29 of Cycle 6; Rituximab SC arm: pre-dose, and on Days 2, 3, 8 ,15, 29 of Cycle 6

Title

Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration

Description

In part 1 of the trial, upon completion of dosing in cycle 6, participants and their treating nurses were asked whether they have a preference of dosing route, IV vs SC

Time Frame

Days 4 to 5 in Cycle 6

Title

Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV

Description

Time Frame

Days 4-5 in Cycle 6

Title

Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV

Description

Time Frame

Days 4-5 in Cycle 6

Title

Part 1: Percentage of Participants With Anti-Rituximab Antibodies

Description

Blood samples for the assessment of antibodies against rituximab (HACAs) were drawn pre-dose at Cycle 5 and Cycle 6 in Part 1 and at each follow up visit until 24 months after the last dose.

Time Frame

Predose at Cycles 5 and 6 and at each follow up visit until 24 months after the last dose

Title

Part 2: Percentage of Participants With Anti-Rituximab Antibodies

Description

In Part 2, samples for the HACA assay were collected at each treatment cycle prior to the administration of rituximab and at each follow-up visit until 24 months after the last dose of rituximab.

Time Frame

Day 0 of Cycle 1 and Day 1 of Cycles 1, 2, 3, 4, 5, and 6 and at each follow-up visit until 24 months after the last dose of rituximab.

Title

Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit

Description

CD 19 is a surface antigen (protein) present on B-lymphocytes.

Time Frame

Day 1 of Cycles 5 and 6 and Follow-up Days 28 and 56 and Follow-up Visits at Months 3, 6, 9, 12, 15,18, 21 and 24

Title

Part 1: Percentage of Participants With Total B-Cell Depletion by Visit

Description

Time Frame

Day 1 pre-dose of Cycles 5 and 6 and Follow-up Days 28 and 56 and Follow-up Visits at Months 3, 6, 9, 12, 15, 18, 21 and 24

Title

Part 2: Total CD19+ B-Cell Counts by Visit

Description

CD 19 is a surface antigen (protein) present on B-lymphocytes.

Time Frame

Cycle 1 pre-dose, 60 minutes post-dose, Days 2 and 3 in Cycle 2, day 1 pre-dose in Cycles 3, 4, 5 and 6, Follow-up Days 28 and 56, and Follow-up Visits at Months 3, 6, 9, 12, 15, and 18 and Withdrawal Visit

Title

Part 2: Percentage of Participants With Total B-Cell Depletion by Visit

Description

Time Frame

Cycle 1 Pre-dose, 60 minutes post-dose, Days 2 and 3 in Cycle 2, day 1 in Cycles 3, 4, 5 and 6, Follow-up Days 28 and 56, and Follow-up Visits at Months 3, 6, 9, 12, 15, and 18 and Withdrawal Visit

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

Fundaleu; Haematology

City

Buenos Aires

ZIP/Postal Code

C1114AAN

Country

Argentina

Facility Name

Cemic; Haematology

City

Buenos Aires

ZIP/Postal Code

C1431FWO

Country

Argentina

Facility Name

HOSPITAL PRIVADO - CENTRO MEDICO DE CÓRDOBA; Dpto Oncología

City

Córdoba

ZIP/Postal Code

5016

Country

Argentina

Facility Name

St George Hospital; Department of Haematology

City

Kogarah

State/Province

New South Wales

ZIP/Postal Code

2217

Country

Australia

Facility Name

Royal Brisbane and Women'S Hospital; Haematology

City

Herston

State/Province

Queensland

ZIP/Postal Code

4029

Country

Australia

Facility Name

Ashford Cancer Center Research

City

Kurralta Park

State/Province

South Australia

ZIP/Postal Code

5037

Country

Australia

Facility Name

Queen Elizabeth Hospital; Haematology

City

Woodville South

State/Province

South Australia

ZIP/Postal Code

5011

Country

Australia

Facility Name

St Vincent'S Hospital; Haematology

City

Fitzroy

State/Province

Victoria

ZIP/Postal Code

3065

Country

Australia

Facility Name

Frankston Hospital; Oncology/Haematology

City

Frankston

State/Province

Victoria

ZIP/Postal Code

3199

Country

Australia

Facility Name

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

City

Passo Fundo

State/Province

ZIP/Postal Code

99010-260

Country

Brazil

Facility Name

Hospital Mae de Deus

City

Porto Alegre

State/Province

ZIP/Postal Code

90470-340

Country

Brazil

Facility Name

Hospital Sirio Libanes; Centro de Oncologia

City

Sao Paulo

State/Province

ZIP/Postal Code

01308-050

Country

Brazil

Facility Name

Hospital das Clinicas - FMUSP

City

Sao Paulo

State/Province

ZIP/Postal Code

05403-000

Country

Brazil

Facility Name

Queen Elizabeth II Health Sciences Centre; Oncology

City

Halifax

State/Province

Nova Scotia

ZIP/Postal Code

B3H 2Y9

Country

Canada

Facility Name

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

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H3T 1E2

Country

Canada

Facility Name

Centre de sante et de services sociaux Rimouski Neigette

City

Rimouski

State/Province

Quebec

ZIP/Postal Code

G5L 5T1

Country

Canada

Facility Name

Centre Hospitalier Universitaire de Sherbrooke

City

Sherbrooke

State/Province

Quebec

ZIP/Postal Code

J1H 5N4

Country

Canada

Facility Name

Instituto Nacional del Cancer

City

Santiago

ZIP/Postal Code

8380000

Country

Chile

Facility Name

Centro Internacional de Estudios Clínicos (CIEC)

City

Santiago

ZIP/Postal Code

8420383

Country

Chile

Facility Name

Clinical Hospital Merkur; Dept of Haematology

City

Zagreb

ZIP/Postal Code

10000

Country

Croatia

Facility Name

University Hospital Center Zagreb; Haematology Department

City

Zagreb

ZIP/Postal Code

10000

Country

Croatia

Facility Name

Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika

City

Brno

ZIP/Postal Code

625 00

Country

Czechia

Facility Name

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

City

Hradec Kralove

ZIP/Postal Code

500 05

Country

Czechia

Facility Name

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

City

Praha 2

ZIP/Postal Code

128 08

Country

Czechia

Facility Name

Centre Francois Baclesse

City

Caen

ZIP/Postal Code

14076

Country

France

Facility Name

Institut J Paolii Calmettes; Onco Hematologie 1

City

Marseille

ZIP/Postal Code

13273

Country

France

Facility Name

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

City

Paris

ZIP/Postal Code

75475

Country

France

Facility Name

Hopital Robert Debre; Hematologie Clinique

City

Reims

ZIP/Postal Code

51092

Country

France

Facility Name

Hopitaux De Brabois; Hematologie Medecine Interne

City

Vandoeuvre Les Nancy

ZIP/Postal Code

54511

Country

France

Facility Name

Onkologische Schwerpunktpraxis Kurfürstendamm

City

Berlin

ZIP/Postal Code

10707

Country

Germany

Facility Name

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

City

Berlin

ZIP/Postal Code

14195

Country

Germany

Facility Name

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

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Klinikum Frankfurt; Medizinische Klinik I

City

Frankfurt an der Oder

ZIP/Postal Code

15236

Country

Germany

Facility Name

Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik

City

Greifswald

ZIP/Postal Code

17475

Country

Germany

Facility Name

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

City

Hannover

ZIP/Postal Code

30171

Country

Germany

Facility Name

Gemeinschaftspraxis Dr. Siehl & Dr. Soeling

City

Kassel

ZIP/Postal Code

34119

Country

Germany

Facility Name

Klinik der Uni zu Köln; Klinik für Innere Medizin

City

Köln

ZIP/Postal Code

50924

Country

Germany

Facility Name

K&K Studien GbR

City

Landshut

ZIP/Postal Code

84028

Country

Germany

Facility Name

Onkologische Schwerpunktpraxis Lübeck

City

Lübeck

ZIP/Postal Code

23562

Country

Germany

Facility Name

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

City

Marburg

ZIP/Postal Code

35037

Country

Germany

Facility Name

Klinikum Grosshadern der LMU

City

Muenchen

ZIP/Postal Code

81377

Country

Germany

Facility Name

Medizinisches Versorgungszentrum MOP

City

München

ZIP/Postal Code

80335

Country

Germany

Facility Name

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

City

Neunkirchen/Saar

ZIP/Postal Code

66538

Country

Germany

Facility Name

Prosper-Hospital, Medizinische Klinik I

City

Recklinghausen

ZIP/Postal Code

45659

Country

Germany

Facility Name

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

City

Athens

ZIP/Postal Code

115 27

Country

Greece

Facility Name

Papageorgiou General Hospital of Thessaloniki; Hematology Clinic

City

Thessaloniki

ZIP/Postal Code

54629

Country

Greece

Facility Name

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

City

Meldola

State/Province

Emilia-Romagna

ZIP/Postal Code

47014

Country

Italy

Facility Name

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

City

Ravenna

State/Province

Emilia-Romagna

ZIP/Postal Code

48100

Country

Italy

Facility Name

Ospedale Infermi Di Rimini; Unità Operativa di Oncologia e Oncoematologia

City

Rimini

State/Province

Emilia-Romagna

ZIP/Postal Code

47900

Country

Italy

Facility Name

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

City

Udine

State/Province

Friuli-Venezia Giulia

ZIP/Postal Code

33100

Country

Italy

Facility Name

Istituto S. Raffaele Monte Tabor; Divisione Ematologia E Utmo

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20132

Country

Italy

Facility Name

ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Struttura Complessa di Ematologia

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20162

Country

Italy

Facility Name

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

City

Novara

State/Province

Piemonte

ZIP/Postal Code

28100

Country

Italy

Facility Name

Policlinico G. B. Rossi; Divisione Di Ematologia

City

Verona

State/Province

Veneto

ZIP/Postal Code

37134

Country

Italy

Facility Name

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

City

Chihuahua

ZIP/Postal Code

31000

Country

Mexico

Facility Name

Hospital General De Culiacan; Servicio De Hematologia

City

Culiacan

ZIP/Postal Code

80230

Country

Mexico

Facility Name

Hospital Universitario Dr. Jose E. Gonzalez; Haematology

City

Monterrey

ZIP/Postal Code

64460

Country

Mexico

Facility Name

Canterbury Health Laboratories; Haematology

City

Christchurch

ZIP/Postal Code

8011

Country

New Zealand

Facility Name

Wellington Hospital; Wellington Blood and Cancer Centre

City

Newtown

ZIP/Postal Code

6021

Country

New Zealand

Facility Name

Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii

City

Gdansk

ZIP/Postal Code

80-952

Country

Poland

Facility Name

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

City

Lublin

ZIP/Postal Code

20-081

Country

Poland

Facility Name

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

City

Warszawa

ZIP/Postal Code

02-781

Country

Poland

Facility Name

Medical Uni of Wroclaw; Hematology

City

Wroclaw

ZIP/Postal Code

50-367

Country

Poland

Facility Name

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

City

Lisboa

ZIP/Postal Code

1600

Country

Portugal

Facility Name

IPO do Porto; Servico de Onco-Hematologia

City

Porto

ZIP/Postal Code

4200-072

Country

Portugal

Facility Name

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

City

Moscow

ZIP/Postal Code

115478

Country

Russian Federation

Facility Name

City Clinical Hospital After Botkin; Hematology

City

Moscow

ZIP/Postal Code

125101

Country

Russian Federation

Facility Name

Haematology Research Center; Haematology

City

Moscow

ZIP/Postal Code

125167

Country

Russian Federation

Facility Name

Penza Regional Oncology Dispensary

City

Penza

ZIP/Postal Code

440071

Country

Russian Federation

Facility Name

Clinical MSCh No1

City

Perm

ZIP/Postal Code

614077

Country

Russian Federation

Facility Name

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

City

Saint-Petersburg

ZIP/Postal Code

197022

Country

Russian Federation

Facility Name

National Oncology Inst. ; Dept. of Haematology

City

Bratislava

ZIP/Postal Code

833 10

Country

Slovakia

Facility Name

University Hospital; Clinic of Hematology & Transfusiology

City

Bratislava

ZIP/Postal Code

851 07

Country

Slovakia

Facility Name

Hospital Universitari Vall d'Hebron; Servicio de Hematologia

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Hospital Universitario de la Princesa; Servicio de Hematologia

City

Madrid

ZIP/Postal Code

28006

Country

Spain

Facility Name

Hospital Universitario Puerta de Hierro; Servicio de Hematologia

City

Madrid

ZIP/Postal Code

28222

Country

Spain

Facility Name

Hospital Clinico Universitario de Salamanca;Servicio de Hematologia

City

Salamanca

ZIP/Postal Code

37007

Country

Spain

Facility Name

Hospital Universitario Virgen del Rocio; Servicio de Hematologia

City

Sevilla

ZIP/Postal Code

41013

Country

Spain

Facility Name

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

City

Toledo

ZIP/Postal Code

45004

Country

Spain

Facility Name

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

City

Valencia

ZIP/Postal Code

46010

Country

Spain

Facility Name

Hacettepe Uni Medical Faculty; Hematology

City

Ankara

ZIP/Postal Code

06100

Country

Turkey

Facility Name

Istanbul University Cerrahpasa Medical Faculty; Hematology Department

City

Istanbul

ZIP/Postal Code

34098

Country

Turkey

Facility Name

Dokuz Eylul Uni ; Hematology

City

Izmir

ZIP/Postal Code

35100

Country

Turkey

Facility Name

Ege University ARGEFAR

City

Izmir

ZIP/Postal Code

35100

Country

Turkey

12. IPD Sharing Statement

Citations:

PubMed Identifier

26947201

Citation

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.

Results Reference

derived

PubMed Identifier

25900065

Citation

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.

Results Reference

derived

PubMed Identifier

24265828

Citation

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.

Results Reference

derived

PubMed Identifier

24002601

Citation

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.

Results Reference

derived

Learn more about this trial

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

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