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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphocytic Leukemia, Chronic
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: rituximab [MabThera]; Drug: rituximab [MabThera]; Drug: rituximab [MabThera]

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1114AAN
    • Fundaleu; Haematology
  • Buenos Aires, Argentina, C1431FWO
    • Cemic; Haematology
  • Córdoba, Argentina, 5016
    • HOSPITAL PRIVADO - CENTRO MEDICO DE CÓRDOBA; Dpto Oncología
• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital; Department of Haematology
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women'S Hospital; Haematology
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Ashford Cancer Center Research
    • Woodville South, South Australia, Australia, 5011
      • Queen Elizabeth Hospital; Haematology
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent'S Hospital; Haematology
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital; Oncology/Haematology
• Brazil
  • RS
    • Passo Fundo, RS, Brazil, 99010-260
      • Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia
    • Porto Alegre, RS, Brazil, 90470-340
      • Hospital Mae de Deus
  • SP
    • Sao Paulo, SP, Brazil, 01308-050
      • Hospital Sirio Libanes; Centro de Oncologia
    • Sao Paulo, SP, Brazil, 05403-000
      • Hospital das Clinicas - FMUSP
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Sciences Centre; Oncology
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
    • Rimouski, Quebec, Canada, G5L 5T1
      • Centre De Sante Et De Services Sociaux Rimouski Neigette
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
• Chile
  • Santiago, Chile, 8420383
    • Centro Internacional de Estudios Clinicos (CIEC)
  • Santiago, Chile, 8380000
    • Instituto Nacional del Cancer
• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital Center Zagreb; Haematology Department
  • Zagreb, Croatia, 10000
    • Clinical Hospital Merkur; Dept of Haematology
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
  • Hradec Kralove, Czechia, 500 05
    • University Hospital and Medical School; IV.Dept. of Internal Medicine and Hematology
  • Praha 2, Czechia, 128 08
    • Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK
• France
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Marseille, France, 13273
    • Institut J Paolii Calmettes; Onco Hematologie 1
  • Paris, France, 75475
    • Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)
  • Reims, France, 51092
    • Hopital Robert Debre; Hematologie Clinique
  • Vandoeuvre Les Nancy, France, 54511
    • Hopitaux De Brabois; Hematologie Medecine Interne
• Germany
  • Berlin, Germany, 10707
    • Onkologische Schwerpunktpraxis Kurfürstendamm
  • Berlin, Germany, 14195
    • Onkologischer Schwerpunkt am Oskar-Helene-Heim; Dres. Herrenberger, Keitel-Wittig u. Kirsch
  • Dresden, Germany, 01307
    • BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie
  • Frankfurt an der Oder, Germany, 15236
    • Klinikum Frankfurt; Medizinische Klinik I
  • Greifswald, Germany, 17475
    • Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik
  • Hannover, Germany, 30171
    • Onkologische Schwerpunktpraxis Dres. Bernd Gaede, Hans-Ulrich Ehlers, Ulrike Rodewig u.w.
  • Kassel, Germany, 34119
    • Gemeinschaftspraxis Dr. Siehl & Dr. Soeling
  • Köln, Germany, 50924
    • Klinik der Uni zu Köln; Klinik für Innere Medizin
  • Landshut, Germany, 84028
    • K&K Studien GbR
  • Lübeck, Germany, 23562
    • Onkologische Schwerpunktpraxis Lübeck
  • Marburg, Germany, 35037
    • Gemeinschaftspraxis Fr. Dr. med. Balser & Hr. Dr. med. Weidenbach
  • Muenchen, Germany, 81377
    • Klinikum Grosshadern der LMU
  • München, Germany, 80335
    • Medizinisches Versorgungszentrum MOP
  • Neunkirchen/Saar, Germany, 66538
    • Gemeinschaftspraxis Dr. med. Holger Klaproth / Dr. med. Anca Astrid Cura
  • Recklinghausen, Germany, 45659
    • Prosper-Hospital, Medizinische Klinik I
• Greece
  • Athens, Greece, 115 27
    • Laiko General Hospital of Athens; A Propedeutical Clinic of Internal Medicine
  • Thessaloniki, Greece, 54629
    • Papageorgiou General Hospital of Thessaloniki; Hematology Clinic
• Italy
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
    • Ravenna, Emilia-Romagna, Italy, 48100
      • Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia
    • Rimini, Emilia-Romagna, Italy, 47900
      • Ospedale Infermi Di Rimini; Unità Operativa di Oncologia e Oncoematologia
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
      • A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Ematologica
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • Istituto S. Raffaele Monte Tabor; Divisione Ematologia E Utmo
    • Milano, Lombardia, Italy, 20162
      • ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Struttura Complessa di Ematologia
  • Piemonte
    • Novara, Piemonte, Italy, 28100
      • Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad
  • Veneto
    • Verona, Veneto, Italy, 37134
      • Policlinico G. B. Rossi; Divisione Di Ematologia
• Mexico
  • Chihuahua, Mexico, 31000
    • Centro Estatal De Cancerologia De Chihuahua; Servicio De Hematologia Banco De Sangre
  • Culiacan, Mexico, 80230
    • Hospital General De Culiacan; Servicio De Hematologia
  • Monterrey, Mexico, 64460
    • Hospital Universitario Dr. Jose E. Gonzalez; Haematology
• New Zealand
  • Christchurch, New Zealand, 8011
    • Canterbury Health Laboratories; Haematology
  • Newtown, New Zealand, 6021
    • Wellington Hospital; Wellington Blood and Cancer Centre
• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne; Klinika Hematologii i Transplantologii
  • Lublin, Poland, 20-081
    • Katedra i Klinika Hematoonkologii i Transplantacji Szpiku; Uniwersytetu Medycznego w Lublinie
  • Warszawa, Poland, 02-781
    • Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Lymphoma Dept.
  • Wroclaw, Poland, 50-367
    • Medical Uni of Wroclaw; Hematology
• Portugal
  • Lisboa, Portugal, 1600
    • Hospital de Santa Maria; Servico de Hematologia e Transplantacao de Medula
  • Porto, Portugal, 4200-072
    • IPO do Porto; Servico de Onco-Hematologia
• Russian Federation
  • Moscow, Russian Federation, 125101
    • City Clinical Hospital After Botkin; Hematology
  • Moscow, Russian Federation, 115478
    • N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
  • Moscow, Russian Federation, 125167
    • Haematology Research Center; Haematology
  • Penza, Russian Federation, 440071
    • Penza Regional Oncology Dispensary
  • Perm, Russian Federation, 614077
    • Clinical MSCh No1
  • Saint-Petersburg, Russian Federation, 197022
    • St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta
• Slovakia
  • Bratislava, Slovakia, 833 10
    • National Oncology Inst. ; Dept. of Haematology
  • Bratislava, Slovakia, 851 07
    • University Hospital; Clinic of Hematology & Transfusiology
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Servicio de Hematologia
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro; Servicio de Hematologia
  • Madrid, Spain, 28006
    • Hospital Universitario de la Princesa; Servicio de Hematologia
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio; Servicio de Hematologia
  • Toledo, Spain, 45004
    • Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Hematología
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe Uni Medical Faculty; Hematology
  • Istanbul, Turkey, 34098
    • Istanbul University Cerrahpasa Medical Faculty; Hematology Department
  • Izmir, Turkey, 35100
    • Dokuz Eylul Uni ; Hematology
  • Izmir, Turkey, 35100
    • Ege University ARGEFAR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Cyclophosphamide; Days 1-3 or Days 1-5 of cycles 1-6; Drug: Fludarabine; Days 1-3 or Days 1-5 of cycles 1-6; Drug: rituximab [MabThera]; One cycle of intravenous MabThera, followed by 5 cycles of subcutaneous MabThera; 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.; Drug: rituximab [MabThera]; 6 cycles of intravenous MabThera
Experimental: 2	Drug: Cyclophosphamide; Days 1-3 or Days 1-5 of cycles 1-6; Drug: Fludarabine; Days 1-3 or Days 1-5 of cycles 1-6; Drug: rituximab [MabThera]; One cycle of intravenous MabThera, followed by 5 cycles of subcutaneous MabThera; 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.; Drug: rituximab [MabThera]; 6 cycles of intravenous MabThera
Experimental: 3	Drug: Cyclophosphamide; Days 1-3 or Days 1-5 of cycles 1-6; Drug: Fludarabine; Days 1-3 or Days 1-5 of cycles 1-6; Drug: rituximab [MabThera]; One cycle of intravenous MabThera, followed by 5 cycles of subcutaneous MabThera; 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.; Drug: rituximab [MabThera]; 6 cycles of intravenous MabThera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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
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.	+/- 25hours around the 28th day post the 5th Cycle of Rituximab administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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
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.	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
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.	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
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.	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
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	Days 4 to 5 in Cycle 6
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.	Days 4-5 in Cycle 6
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.	Days 4-5 in Cycle 6
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.	Predose at Cycles 5 and 6 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.	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.
Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit	CD 19 is a surface antigen (protein) present on B-lymphocytes.	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
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.	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
Part 2: Total CD19+ B-Cell Counts by Visit	CD 19 is a surface antigen (protein) present on B-lymphocytes.	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
Part 2: 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.	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2011
• Primary Completion (Actual): May 7, 2014
• Study Completion (Actual): November 17, 2017

Study Registration Dates

• First Submitted: February 8, 2011
• First Submitted That Met QC Criteria: February 8, 2011
• First Posted (Estimate): February 9, 2011

Study Record Updates

• Last Update Posted (Actual): December 19, 2018
• Last Update Submitted That Met QC Criteria: November 17, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Rituximab; Fludarabine
• Other Study ID Numbers: BO25341; 2010-021380-32 (EudraCT Number)