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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01292603

Collaborator

(none)

240

Enrollment

84

Locations

3

Arms

79

Actual Duration (Months)

2.9

Patients Per Site

0

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphocytic Leukemia, Chronic	Drug: Cyclophosphamide Drug: Fludarabine Drug: rituximab [MabThera] Drug: rituximab [MabThera] Drug: rituximab [MabThera]	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

240 participants

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 18, 2011

Actual Primary Completion Date :

May 7, 2014

Actual Study Completion Date :

Nov 17, 2017

Arms and Interventions

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]

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.

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]

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

Outcome Measures

Primary Outcome Measures

Part 1: Subcutaneous Rituximab Dose Resulting in Trough Concentration (Ctrough) Levels Non-Inferior to Intravenous Rituximab [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]
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 [+/- 25hours around the 28th day post the 5th Cycle of Rituximab administration]
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 [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]
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 [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]
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 [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]
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 [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]
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 [Days 4 to 5 in Cycle 6]
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 [Days 4-5 in Cycle 6]
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 [Days 4-5 in Cycle 6]
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 [Predose at Cycles 5 and 6 and at each follow up visit until 24 months after the last dose]
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 [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.]
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 [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]
CD 19 is a surface antigen (protein) present on B-lymphocytes.
Part 1: Percentage of Participants With Total B-Cell Depletion by Visit [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]
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 [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]
CD 19 is a surface antigen (protein) present on B-lymphocytes.
Part 2: Percentage of Participants With Total B-Cell Depletion by Visit [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]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01292603

Other Study ID Numbers:

BO25341
2010-021380-32

First Posted:

Feb 9, 2011

Last Update Posted:

Dec 19, 2018

Last Verified:

Nov 1, 2018

Additional relevant MeSH terms:

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Cyclophosphamide

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	In Part 1 a single dose of subcutaneous (SC) rituximab was administered at Cycle 6 to select a dose resulting in trough concentration (Ctrough) non-inferior to intravenous (IV) dose. In Part 2, participants were randomized to receive rituximab IV or SC, to demonstrate non-inferiority of rituximab Ctrough levels of SC dose compared with IV dose.

Arm/Group Title	Part 1: Rituximab SC 1400 Milligrams (mg)	Part 1: Rituximab SC 1600 mg	Part 1: Rituximab SC 1870 mg	Part 1: No SC Dose Received	Part 2 : Rituximab IV 500 mg/m^2	Part 2: Rituximab SC 1600 mg
Arm/Group Description	Participant could have been enrolled any time during their treatment with rituximab IV in combination with fludarabine/cyclophosphamide (FC) prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 milligrams per square meter (mg/m^2) on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participant could have been enrolled any time during their treatment with rituximab IV in combination with FC prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participant could have been enrolled any time during their treatment with rituximab IV in combination with FC prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1870 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	These participants were withdrawn prior to SC treatment.	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Period Title: Part 1: Pilot Dose Selection Period
STARTED	16	17	23	8	0	0
COMPLETED	16	17	23	0	0	0
NOT COMPLETED	0	0	0	8	0	0
Period Title: Part 1: Pilot Dose Selection Period
STARTED	16	17	23	8	0	0
COMPLETED	10	10	17	7	0	0
NOT COMPLETED	6	7	6	1	0	0
Period Title: Part 1: Pilot Dose Selection Period
STARTED	0	0	0	0	88	88
COMPLETED	0	0	0	0	72	73
NOT COMPLETED	0	0	0	0	16	15
Period Title: Part 1: Pilot Dose Selection Period
STARTED	0	0	0	0	87	87
COMPLETED	0	0	0	0	68	75
NOT COMPLETED	0	0	0	0	19	12
Period Title: Part 1: Pilot Dose Selection Period
STARTED	16	17	23	8	88	88
COMPLETED	13	16	20	7	72	78
NOT COMPLETED	3	1	3	1	16	10

Baseline Characteristics

Arm/Group Title	Part 1: Rituximab SC 1400 Milligrams (mg)	Part 1: Rituximab SC 1600 mg	Part 1: Rituximab SC 1870 mg	Part 2 : Rituximab IV 500 mg/m^2	Part 2: Rituximab SC 1600 mg	Total
Arm/Group Description	Participant could have been enrolled any time during their treatment with rituximab IV in combination with fludarabine/cyclophosphamide (FC) prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participant could have been enrolled any time during their treatment with rituximab IV in combination with FC prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participant could have been enrolled any time during their treatment with rituximab IV in combination with FC prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1870 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Total of all reporting groups
Overall Participants	16	17	22	89	85	229
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.6 (10.13)	60.4 (8.18)	56.9 (6.79)	58.7 (9.03)	59.1 (8.87)	58.8 (8.8)
Sex: Female, Male (Count of Participants)
Female	6 37.5%	2 11.8%	7 31.8%	36 40.4%	25 29.4%	76 33.2%
Male	10 62.5%	15 88.2%	15 68.2%	53 59.6%	60 70.6%	153 66.8%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description
Enrolled (non-randomized) Pharmacokinetic Evaluable Population (Part 1) included all participants from Part 1 who did not significantly violate the inclusion or exclusion criteria, deviate significantly from the protocol or have unavailable or incomplete data which could influence the pharmacokinetic analysis.

Arm/Group Title	Part 1: Rituximab SC
Arm/Group Description	Participant could have been enrolled any time during their treatment with rituximab IV in combination with FC prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400, 1600 or 1870 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	56
Number [mg]	1600

2. Primary Outcome

Title	Part 2: Rituximab C Trough Levels at Cycle 5
Description	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.
Time Frame	+/- 25hours around the 28th day post the 5th Cycle of Rituximab administration

Outcome Measure Data

Analysis Population Description
Only participants who entered Part 2 of the study and had pharmacokinetic (PK) data available were included in the analysis.

Arm/Group Title	Part 2 : Rituximab IV 500 mg/m^2	Part 2: Rituximab SC 1600 mg
Arm/Group Description	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	69	65
Geometric Mean (Geometric Coefficient of Variation) [μg/mL]	61.50 (89.54)	97.53 (55.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Rituximab SC, Part 2: Rituximab SC 1600 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A standard non-inferiority margin of 0.8 for the ratio of Ctrough was used. The non-inferiority limit corresponds to a maximal 20 percent (%) loss in Ctrough which is considered acceptable given the high variability and range of Ctrough data, with an 80% power and a one-sided alpha of 0.05.

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	1.533
	Confidence Interval	(2-Sided) 90% 1.269 to 1.852
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio based on geometric scale and adjusted for the covariate tumor load at baseline.

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Only participants who entered Part 2 of the study and had PK data available were included in the analysis.

Arm/Group Title	Part 2 : Rituximab IV 500 mg/m^2	Part 2: Rituximab SC 1600 mg
Arm/Group Description	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	58	51
Geometric Mean (Geometric Coefficient of Variation) [μg*day/mL]	3630.43 (38.61)	4088.78 (37.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Rituximab SC, Part 2: Rituximab SC 1600 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	1.102
	Confidence Interval	(2-Sided) 90% 0.979 to 1.242
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio based on geometric scale and adjusted for the covariate tumor load at baseline.

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Only participants who entered Part 2 of the study and had PK data available were included in the analysis.

Arm/Group Title	Part 2 : Rituximab IV 500 mg/m^2	Part 2: Rituximab SC 1600 mg
Arm/Group Description	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	58	51
Geometric Mean (Geometric Coefficient of Variation) [μg/mL]	279.78 (23.96)	202.16 (36.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Rituximab SC, Part 2: Rituximab SC 1600 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	0.719
	Confidence Interval	(2-Sided) 90% 0.653 to 0.792
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio based on geometric scale and adjusted for the covariate tumor load at baseline.

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Only participants who entered Part 2 of the study and had PK data available were included in the analysis.

Arm/Group Title	Part 2 : Rituximab IV 500 mg/m^2	Part 2: Rituximab SC 1600 mg
Arm/Group Description	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	58	51
Geometric Mean (Geometric Coefficient of Variation) [days]	0.22 (130.84)	3.14 (87.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Rituximab SC, Part 2: Rituximab SC 1600 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	14.884
	Confidence Interval	(2-Sided) 90% 11.215 to 19.755
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio based on geometric scale and adjusted for the covariate tumor load at baseline.

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Only participants who entered Part 2 of the study and had PK data available were included in the analysis.

Arm/Group Title	Part 2 : Rituximab IV 500 mg/m^2	Part 2: Rituximab SC 1600 mg
Arm/Group Description	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	58	50
Geometric Mean (Geometric Coefficient of Variation) [days]	30.09 (41.86)	30.71 (33.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Rituximab SC, Part 2: Rituximab SC 1600 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Adjusted geometric mean ratio
	Estimated Value	1.010
	Confidence Interval	(2-Sided) 90% 0.895 to 1.139
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio based on geometric scale and adjusted for the covariate tumor load at baseline.

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
All participants in Part 1 were included in this analysis including 8 participants that did not receive SC rituximab.

Arm/Group Title	Part 1: Rituximab SC 1400 mg	Part 1: Rituximab SC 1600 mg	Part 1: Rituximab SC 1870 mg
Arm/Group Description	Participant could have been enrolled any time during treatment with rituximab IV in combination with fludarabine/cyclophosphamide (FC) prior to Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1600 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1870 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	16	17	23
Participants who preferred SC	88.0 550%	100.0 588.2%	91.0 413.6%
Participants who preferred IV	13.0 81.3%	0.0 0%	9.0 40.9%
Nurses who preferred SC	88.0 550%	100.0 588.2%	91.0 413.6%
Nurses who preferred IV	13.0 81.3%	0.0 0%	9.0 40.9%

8. Secondary Outcome

Title	Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV
Description	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.
Time Frame	Days 4-5 in Cycle 6

Outcome Measure Data

Analysis Population Description
All the physicians and nurses who responded to the questionnaire were included in the analysis.

Arm/Group Title	Part 2 : Rituximab IV 500 mg/m^2	Part 2: Rituximab SC 1600 mg
Arm/Group Description	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	78	81
Nurse: 4 or more hours	21.0 131.3%	21.0 123.5%
Nurse: At least 3 hours but less than 4 hours	23.0 143.8%	29.0 170.6%
Nurse: At least 2 hours but less than 3 hours	26.0 162.5%	23.0 135.3%
Nurse: At least 1 hour but less than 2 hours	17.0 106.3%	11.0 64.7%
Nurse: Less than 1 hour	13.0 81.3%	16.0 94.1%
Physician: 4 or more hours	21.0 131.3%	22.0 129.4%
Physician: At least 3 hours but less than 4 hours	18.0 112.5%	21.0 123.5%
Physician: At least 2 hours but less than 3 hours	24.0 150%	26.0 152.9%
Physician: At least 1 hour but less than 2 hours	22.0 137.5%	19.0 111.8%
Physician: Less than 1 hour	10.0 62.5%	7.0 41.2%

9. Secondary Outcome

Title	Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV
Description	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.
Time Frame	Days 4-5 in Cycle 6

Outcome Measure Data

Analysis Population Description
All the physicians and nurses who responded to the questionnaire were included in the analysis.

Arm/Group Title	Part 2 : Rituximab IV 500 mg/m^2	Part 2: Rituximab SC 1600 mg
Arm/Group Description	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	78	81
Nurse: Rituximab SC is much more convenient	81.0 506.3%	77.0 452.9%
Nurse: Rituximab SC is a little more convenient	7.0 43.8%	9.0 52.9%
Nurse: Both formulations are equally convenient	9.0 56.3%	4.0 23.5%
Nurse: Rituximab IV is a little more convenient	3.0 18.8%	10.0 58.8%
Nurse: Rituximab IV is much more convenient	0.0 0%	0.0 0%
Physician: Rituximab SC is much more convenient	78.0 487.5%	80.0 470.6%
Physician: Rituximab SC a little more convenient	15.0 93.8%	14.0 82.4%
Physician: Both formulations equally convenient	6.0 37.5%	6.0 35.3%
Physician: Rituximab IV a little more convenient	0.0 0%	0.0 0%
Physician: Rituximab IV is much more convenient	0.0 0%	0.0 0%

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Safety Analysis Population (SAP): all participants who received at least one dose of study medication, whether prematurely withdrawn from the study or not. This included 8 participants that did not receive SC rituximab. n = number of participants analyzed.

Arm/Group Title	Part 1: Rituximab SC
Arm/Group Description	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400, 1600 or 1870 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	64
Pre-Dose Cycle 5: positive for HACAs (n=59)	0.0 0%
Pre-Dose Cycle 5: negative for HACAs (n=59)	100.0 625%
Post-Dose: positive for HACAs (n=61)	5.0 31.3%
Post-Dose: negative for HACAs (n=61)	95.1 594.4%

11. Secondary Outcome

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.

Outcome Measure Data

Analysis Population Description
SAP; n = number of participants analyzed for the specific parameter.

Arm/Group Title	Part 2 : Rituximab IV 500 mg/m^2	Part 2: Rituximab SC 1600 mg
Arm/Group Description	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	89	85
Baseline pre Cycle 1: positive for HACAs (n=87,85)	0.0 0%	2.4 14.1%
Baseline pre Cycle 1: negative for HACAs (n=87,85)	100.0 625%	97.6 574.1%
Post-Baseline: positive for HACAs (n=89,85)	15.0 93.8%	12.0 70.6%
Post-Baseline: negative for HACAs (n=89,85)	85.0 531.3%	88.0 517.6%

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Part 1 SAP; n = number of participants analyzed at the specified visit.

Arm/Group Title	Part 1: Rituximab SC 1400 Milligrams (mg)	Part 1: Rituximab SC 1600 mg	Part 1: Rituximab SC 1870 mg	Part 1: Rituximab SC 1000 mg	Part 1: No SC Dose Received
Arm/Group Description	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1600 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1870 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	One participant enrolled in the rituximab SC 1870 mg subcohort received 1000 mg rituximab SC during Cycle 6 in error. Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1000 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	These participants were withdrawn prior to SC treatment.
Measure Participants	16	17	22	1	8
Cycle 5 Day 1 (n=15,13,19,1,2)	2	3	0	84	2
Cycle 6 Day 1 (n=15,14,18,1,0)	1	2	1	27	NA
FU 28 Day Visit (n=15,11,19,1,0)	2	2	0	7	NA
FU 56 Day Visit (n=15,9,15,1,0)	1	3	0	14	NA
FU 3 Month Visit (n=16,8,18,0,0)	3	1	1	NA	NA
FU 6 Month Visit (n=15,13,17,1,0)	2	1	2	51	NA
FU 9 Month Visit (n=15,13,15,1,0)	66	19	29	74	NA
FU 12 Month Visit (n=14,14,20,0,0)	126	31	90	NA	NA
FU 15 Month Visit (n=14,11,15,0,0)	175	41	106	NA	NA
FU 18 Month Visit (n=13,14,15,0,0)	175	82	189	NA	NA
FU 21 Month Visit (n=13,12,16,0,0)	128	78	149	NA	NA
FU 24 Month Visit(n=12, 4,16,0,0)	238	110	232	NA	NA

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Part 1 SAP; n = number of participants analyzed at the specified visit.

Arm/Group Title	Part 1: Rituximab SC 1400 mg	Part 1: Rituximab SC 1600 mg	Part 1: Rituximab SC 1870 mg	Rituximab SC 1000 mg	Part 1: No SC Dose Received
Arm/Group Description	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1600 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1870 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1000 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	These participants were withdrawn prior to SC treatment.
Measure Participants	16	17	22	1	8
Cycle 5 Day 1 (n=15,1319,1,2)	93.3 583.1%	92.3 542.9%	100.0 454.5%	0.0 0%	100.0 117.6%
Cycle 6 Day 1(n= 15,14,18,1,0)	93.3 583.1%	100.0 588.2%	100.0 454.5%	100.0 112.4%	NA NaN
FU 28 Day Visit (n=15,11,19,1,0)	93.3 583.1%	100.0 588.2%	100.0 454.5%	100.0 112.4%	NA NaN
FU 56 Day Visit (n=15,9,15,1,0)	93.3 583.1%	100.0 588.2%	100.0 454.5%	100.0 112.4%	NA NaN
FU 3 Month Visit (n=16,8,18,0,0)	93.8 586.3%	100.0 588.2%	100.0 454.5%	NA NaN	NA NaN
FU 6 Month Visit (n=15,13,17,1,0)	86.7 541.9%	92.3 542.9%	94.1 427.7%	100.0 112.4%	NA NaN
FU 9 Month Visit (n=15,13,15,1,0)	53.3 333.1%	84.6 497.6%	60.0 272.7%	100.0 112.4%	NA NaN
FU 12 Month Visit (n=14,14,20,0,0)	28.6 178.8%	85.7 504.1%	45.0 204.5%	NA NaN	NA NaN
FU 15 Month Visit (n=14,11,15,0,0)	35.7 223.1%	54.5 320.6%	40.0 181.8%	NA NaN	NA NaN
FU 18 Month Visit (n=13,14,15,0,0)	30.8 192.5%	50.0 294.1%	26.7 121.4%	NA NaN	NA NaN
FU 21 Month Visit (n=13,12,16,0,0)	30.8 192.5%	50.0 294.1%	18.8 85.5%	NA NaN	NA NaN
FU 24 Month Visit (n=12,14,16,0,0)	25.0 156.3%	21.4 125.9%	18.8 85.5%	NA NaN	NA NaN

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Part 2 SAP; n = number of participants analyzed at the specified visit.

Arm/Group Title	Part 2 : Rituximab IV 500 mg/m^2	Part 2: Rituximab SC 1600 mg
Arm/Group Description	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	89	85
Cycle 1 - Baseline (n=80,80)	68905	50565
Cycle 2 - Pre-dose (n=71,74)	338	253
Cycle 2 - Post-dose (n=65, 66)	163	168
Cycle 2 Day 2 (n=54, 59)	154	266
Cycle 2 Day 3 (n=48, 54)	87	125
Cycle 3 Day 1 (n=67,68)	12	8
Cycle 4 Day 1 (n=71,69)	4	4
Cycle 5 Day 1 (n=68,67)	2	2
Cycle 6 Day 1 (n=71,64)	3	3
FU 28 Day Visit (n=66,64)	2	2
FU 56 Day Visit (n=63,67)	2	2
FU 3 Month Visit (n=67,67)	2	2
FU 6 Month Visit (n=60,69)	3	3
FU 9 Month Visit (n=65,64)	35	30
FU 12 Month Visit (n=60,61)	91	104
FU 15 Month Visit (n=59,60)	135	171
FU 18 Month Visit (n=57,58)	134	223
FU 21 Month Visit (n=55,52)	171	277
FU 24 Month Visit (n=56,51)	214	256
Withdrawn/Termination (n=17,15)	150	6

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Part 2 SAP; n= number of participants analyzed at the specified visit.

Arm/Group Title	Part 2 : Rituximab IV 500 mg/m^2	Part 2: Rituximab SC 1600 mg
Arm/Group Description	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).	Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
Measure Participants	89	85
Cycle 1 - Baseline (n=80,80))	0.0 0%	0.0 0%
Cycle 2 - Pre-dose (n=71, 74)	23.9 149.4%	31.1 182.9%
Cycle 2 - Post-dose (n=65, 66)	32.3 201.9%	37.9 222.9%
Cycle 2 Day 2 (n=54, 59)	35.2 220%	30.5 179.4%
Cycle 2 Day 3 (n=48, 54)	50.0 312.5%	37.0 217.6%
Cycle 3 Day 1 (n=67,68)	73.1 456.9%	76.5 450%
Cycle 4 Day 1 (n=71,69)	83.1 519.4%	84.1 494.7%
Cycle 5 Day 1 (n=68,67)	88.2 551.3%	89.6 527.1%
Cycle 6 Day 1 (n=71,64)	95.8 598.8%	95.3 560.6%
FU 28 Day Visit (n=66,64)	95.5 596.9%	96.9 570%
FU 56 Day Visit (n=63,67)	92.1 575.6%	97.0 570.6%
FU 3 Month Visit (n=67,67)	95.5 596.9%	92.5 544.1%
FU 6 Month Visit (n=60,69)	88.3 551.9%	91.3 537.1%
FU 9 Month Visit (n=65,64)	66.2 413.8%	70.3 413.5%
FU 12 Month Visit (n=60,61)	43.3 270.6%	42.6 250.6%
FU 15 Month Visit (n=59,60)	33.9 211.9%	30.0 176.5%
FU 18 Month Visit (n=57,58)	24.6 153.8%	25.9 152.4%
FU 21 Month Visit (n=55,52)	14.5 90.6%	19.2 112.9%
FU 24 Month Visit (n=56,51)	10.7 66.9%	15.7 92.4%
Withdrawn/Termination (n=17,15)	41.2 257.5%	73.3 431.2%

Adverse Events

	Part 1: Rituximab SC 1400 mg		Part 1: Rituximab SC 1600 mg		Part 1: Rituximab SC 1870 mg		Part 1: Rituximab SC 1000 mg		Part 1: No SC Dose Received		Part 2 : Rituximab IV 500 mg/m^2		Part 2: Rituximab SC 1600 mg
Time Frame	Adverse Events were recorded from the time of initiation of treatment until 28 days after completion of study treatment in Cycle 6.
Adverse Event Reporting Description	New infections and all unrelated SAEs were reported until 9 months after the last dose of study treatment. All related SAEs were reported indefinitely. Secondary malignancies were reported until the end of the study or initiation of a new anti-leukemia treatment, whichever was earlier.

Arm/Group Title	Part 1: Rituximab SC 1400 mg		Part 1: Rituximab SC 1600 mg		Part 1: Rituximab SC 1870 mg		Part 1: Rituximab SC 1000 mg		Part 1: No SC Dose Received		Part 2 : Rituximab IV 500 mg/m^2		Part 2: Rituximab SC 1600 mg
Arm/Group Description	Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1400 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).		Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1600 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).		PParticipant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1870 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).		One participant enrolled in the rituximab SC 1870 mg subcohort received 1000 mg rituximab SC during Cycle 6 in error. Participant could have been enrolled any time during treatment with rituximab IV in combination with FC before Cycle 5. Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 1 or Day 0 (according to local practice) Cycles 2-5: IV rituximab 500 mg/m^2 on Day 1 Cycle 6: SC rituximab 1000 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).		These participants were withdrawn prior to SC treatment.		Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: IV rituximab 500 mg/m^2 on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).		Participants received the following in 28-day cycles. Cycle 1: IV rituximab 375 mg/m^2 on Day 0 Cycles 2-6: SC rituximab 1600 mg on Day 1 Cycles 1-6: IV fludarabine 25 mg/m^2 on Days 1-3 (or as an oral dose of 24 mg/m^2 on Days 1-5 or 30-40 mg/m^2 on Days 1-3), and IV cyclophosphamide 250 mg/m^2 on Days 1-3 (or as an oral dose of 150 mg/m^2 on Days 1-5 or 200-250 mg/m^2 on Days 1-3).
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part 1: Rituximab SC 1400 mg		Part 1: Rituximab SC 1600 mg		Part 1: Rituximab SC 1870 mg		Part 1: Rituximab SC 1000 mg		Part 1: No SC Dose Received		Part 2 : Rituximab IV 500 mg/m^2		Part 2: Rituximab SC 1600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/16 (31.3%)		8/17 (47.1%)		4/22 (18.2%)		1/1 (100%)		3/8 (37.5%)		35/89 (39.3%)		32/85 (37.6%)
Blood and lymphatic system disorders
Febrile Neutropenia	0/16 (0%)		1/17 (5.9%)		2/22 (9.1%)		1/1 (100%)		1/8 (12.5%)		4/89 (4.5%)		9/85 (10.6%)
Anaemia	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		3/89 (3.4%)		0/85 (0%)
Bone Marrow Failure	0/16 (0%)		0/17 (0%)		0/22 (0%)		1/1 (100%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Neutropenia	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		8/89 (9%)		1/85 (1.2%)
Thrombocytopenia	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Haemolytic Anaemia	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		1/85 (1.2%)
Leukopenia	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		1/85 (1.2%)
Pancytopenia	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Cardiac disorders
Cardiac Failure	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Arrhythmia	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
MYOCARDIAL INFARCTION	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
TACHYCARDIA	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Ear and labyrinth disorders
Vertigo	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Eye disorders
Diabetic Retinal Oedema	0/16 (0%)		0/17 (0%)		1/22 (4.5%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Gastrointestinal disorders
Diarrhoea	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Neutropenic Colitis	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
ENTEROCOLITIS	0/16 (0%)		0/17 (0%)		0/22 (0%)		1/1 (100%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
ANAL ULCER	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
MOUTH ULCERATION	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
General disorders
Pyrexia	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		1/89 (1.1%)		3/85 (3.5%)
Death	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		1/85 (1.2%)
Localised Oedema	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Hepatobiliary disorders
Cholecystitis	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Cholelithiasis	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Hepatitis Toxic	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Immune system disorders
Drug Hypersensitivity	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Hypersensitivity	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		0/89 (0%)		0/85 (0%)
Infections and infestations
Peumonia	1/16 (6.3%)		1/17 (5.9%)		1/22 (4.5%)		0/1 (0%)		1/8 (12.5%)		3/89 (3.4%)		2/85 (2.4%)
Gastroenteritis	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Pelvic Infection	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Skin Infection	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Upper Respiratory Tract Infection	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		2/89 (2.2%)		1/85 (1.2%)
Lower Respiratory Tract Infection	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		2/89 (2.2%)		0/85 (0%)
Cellulitis	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Hepatitis B	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Influenza	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Listeriosis	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Lung Infection	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Meningitis	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Meningitis Cryptococcal	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Oesophageal Infection	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Progressive Multifocal Leukoencephalopathy	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Pulpitis Dental	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Respiratory tract infection	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Tuberculosis	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Wound Infection	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
BACTERIAL SEPSIS	0/16 (0%)		0/17 (0%)		0/22 (0%)		1/1 (100%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
BARTHOLINITIS	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
BRONCHITIS	0/16 (0%)		0/17 (0%)		0/22 (0%)		1/1 (100%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
BRONCHOPULMONARY ASPERGILLOSIS	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
SEPTIC SHOCK	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
STAPHYLOCOCCAL INFECTION	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
VARICELLA ZOSTER VIRUS INFECTION	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Injury, poisoning and procedural complications
Wound Dehiscene	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Meniscus Injury	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Metabolism and nutrition disorders
Tumor Lysis Syndrome	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		0/89 (0%)		0/85 (0%)
Musculoskeletal and connective tissue disorders
Osteitis	0/16 (0%)		0/17 (0%)		1/22 (4.5%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Pain in extremity	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma Gastric	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Brain Neoplasm	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Malignant Melanoma	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Metastases to Peritoneum	0/16 (0%)		0/17 (0%)		1/22 (4.5%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Squamous Cell Carcinoma	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
MYELODYSPLASTIC SYNDROME	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
PROSTATE CANCER	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
BASAL CELL CARCINOMA	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		3/89 (3.4%)		1/85 (1.2%)
BOWEN'S DISEASE	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
BREAST CANCER	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
DIFFUSE LARGE B-CELL LYMPHOMA	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
HODGKIN'S DISEASE	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
METASTATIC SQUAMOUS CELL CARCINOMA	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
PAPILLARY THYROID CANCER	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
REFRACTORY ANAEMIA WITH AN EXCESS OF BLASTS	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
SQUAMOUS CELL CARCINOMA OF SKIN	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
THYROID CANCER	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Nervous system disorders
Guillain- Barre Syndrome	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		0/89 (0%)		0/85 (0%)
Meralgia Paraesthetica	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Syncope	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
ENCEPHALITIS AUTOIMMUNE	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Renal and urinary disorders
Cystitis Haemorrhagic	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Nephrolithiasis	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
ACUTE KIDNEY INJURY	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Respiratory, thoracic and mediastinal disorders
Interstitial Lung Disease	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Pulmonary Embolism	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Bronchitis Chronic	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Dyspnoea	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Hypoxia	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
ACUTE RESPIRATORY FAILURE	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		0/89 (0%)		0/85 (0%)
Skin and subcutaneous tissue disorders
Dermatitis Allergic	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Rash Maculo- Papular	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		1/85 (1.2%)
Vascular disorders
Hypertension	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		0/85 (0%)
Other (Not Including Serious) Adverse Events
	Part 1: Rituximab SC 1400 mg		Part 1: Rituximab SC 1600 mg		Part 1: Rituximab SC 1870 mg		Part 1: Rituximab SC 1000 mg		Part 1: No SC Dose Received		Part 2 : Rituximab IV 500 mg/m^2		Part 2: Rituximab SC 1600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/16 (81.3%)		16/17 (94.1%)		21/22 (95.5%)		1/1 (100%)		7/8 (87.5%)		80/89 (89.9%)		81/85 (95.3%)
Blood and lymphatic system disorders
Neutropenia	7/16 (43.8%)		8/17 (47.1%)		9/22 (40.9%)		1/1 (100%)		3/8 (37.5%)		51/89 (57.3%)		54/85 (63.5%)
Leukopenia	3/16 (18.8%)		6/17 (35.3%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		15/89 (16.9%)		16/85 (18.8%)
Anaemia	2/16 (12.5%)		2/17 (11.8%)		1/22 (4.5%)		1/1 (100%)		2/8 (25%)		21/89 (23.6%)		11/85 (12.9%)
Thrombocytopenia	0/16 (0%)		3/17 (17.6%)		2/22 (9.1%)		1/1 (100%)		1/8 (12.5%)		25/89 (28.1%)		20/85 (23.5%)
Agranulocytosis	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Febrile Neutropenia	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Granulocytopenia	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Cardiac disorders
Palpitations	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Tachycardia	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Eye disorders
Diplopia	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		0/89 (0%)		0/85 (0%)
Ocular hyperaemia	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Gastrointestinal disorders
Nausea	2/16 (12.5%)		6/17 (35.3%)		4/22 (18.2%)		0/1 (0%)		2/8 (25%)		31/89 (34.8%)		32/85 (37.6%)
Vomiting	2/16 (12.5%)		2/17 (11.8%)		7/22 (31.8%)		0/1 (0%)		2/8 (25%)		20/89 (22.5%)		18/85 (21.2%)
Diarrhoea	1/16 (6.3%)		4/17 (23.5%)		3/22 (13.6%)		0/1 (0%)		1/8 (12.5%)		9/89 (10.1%)		10/85 (11.8%)
Abdominal pain upper	0/16 (0%)		2/17 (11.8%)		2/22 (9.1%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Constipation	1/16 (6.3%)		2/17 (11.8%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		7/89 (7.9%)		7/85 (8.2%)
Abdominal pain	2/16 (12.5%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		5/89 (5.6%)		7/85 (8.2%)
Dyspepsia	0/16 (0%)		1/17 (5.9%)		1/22 (4.5%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Gastrooesophageal reflux disease	1/16 (6.3%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Mouth ulceration	0/16 (0%)		2/17 (11.8%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Abdominal discomfort	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Gingival erythema	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Gingival pain	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Haemorrhoids	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Odynophagia	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
DYSCHEZIA	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
General disorders
Pyrexia	1/16 (6.3%)		5/17 (29.4%)		1/22 (4.5%)		0/1 (0%)		1/8 (12.5%)		23/89 (25.8%)		26/85 (30.6%)
Chills	1/16 (6.3%)		3/17 (17.6%)		1/22 (4.5%)		0/1 (0%)		1/8 (12.5%)		9/89 (10.1%)		12/85 (14.1%)
Injection site pain	0/16 (0%)		3/17 (17.6%)		3/22 (13.6%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		14/85 (16.5%)
Injection site erythema	0/16 (0%)		2/17 (11.8%)		4/22 (18.2%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		22/85 (25.9%)
Asthenia	1/16 (6.3%)		2/17 (11.8%)		1/22 (4.5%)		0/1 (0%)		0/8 (0%)		16/89 (18%)		8/85 (9.4%)
Fatigue	0/16 (0%)		3/17 (17.6%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		9/89 (10.1%)		9/85 (10.6%)
Chest discomfort	1/16 (6.3%)		2/17 (11.8%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Chest pain	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Feeling hot	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Injection site discolouration	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Injection site swelling	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Oedema Peripheral	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
GAIT DISTURBANCE	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Hepatobiliary disorders
Hepatotoxicity	1/16 (6.3%)		0/17 (0%)		1/22 (4.5%)		0/1 (0%)		1/8 (12.5%)		0/89 (0%)		0/85 (0%)
Infections and infestations
Sinusitis	0/16 (0%)		2/17 (11.8%)		4/22 (18.2%)		0/1 (0%)		0/8 (0%)		5/89 (5.6%)		3/85 (3.5%)
Nasopharyngitis	1/16 (6.3%)		0/17 (0%)		1/22 (4.5%)		0/1 (0%)		1/8 (12.5%)		6/89 (6.7%)		4/85 (4.7%)
Upper respiratory tract infection	0/16 (0%)		1/17 (5.9%)		3/22 (13.6%)		0/1 (0%)		0/8 (0%)		13/89 (14.6%)		10/85 (11.8%)
Herpes zoster	2/16 (12.5%)		2/17 (11.8%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		5/89 (5.6%)		4/85 (4.7%)
Urinary tract infection	1/16 (6.3%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		7/89 (7.9%)		2/85 (2.4%)
Bronchitis	1/16 (6.3%)		0/17 (0%)		1/22 (4.5%)		0/1 (0%)		0/8 (0%)		8/89 (9%)		7/85 (8.2%)
Rhinitis	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Fungal infection	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Gastroenteritis viral	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Giardiasis	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Laryngitis	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Respiratory tract infection	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		3/89 (3.4%)		7/85 (8.2%)
Upper respiratory tract infection bacterial	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Vulvovaginal candidiasis	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Vulvovaginitis trichomonal	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Pneumonia	0/16 (0%)		0/17 (0%)		2/22 (9.1%)		0/1 (0%)		1/8 (12.5%)		0/89 (0%)		0/85 (0%)
Injury, poisoning and procedural complications
Procedural pain	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Investigations
Weight decreased	0/16 (0%)		1/17 (5.9%)		1/22 (4.5%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Immunoglobulins decreased	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Serum ferritin decreased	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	1/16 (6.3%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		0/89 (0%)		0/85 (0%)
Hypokalaemia	1/16 (6.3%)		1/17 (5.9%)		1/22 (4.5%)		0/1 (0%)		1/8 (12.5%)		5/89 (5.6%)		2/85 (2.4%)
Decreased appetite	0/16 (0%)		2/17 (11.8%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		0/89 (0%)		0/85 (0%)
Diabetes mellitus	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Hypomagnesaemia	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Type 2 Diabetes Mellitus	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Musculoskeletal discomfort	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Myalgia	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Arthralgia	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		1/89 (1.1%)		10/85 (11.8%)
Bone pain	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		2/89 (2.2%)		5/85 (5.9%)
Pain in extremity	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		2/89 (2.2%)		5/85 (5.9%)
Back Pain	0/16 (0%)		1/17 (5.9%)		1/22 (4.5%)		0/1 (0%)		1/8 (12.5%)		0/89 (0%)		0/85 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Haemangioma	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Mycosis fungoides	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Renal oncocytoma	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Nervous system disorders
Headache	2/16 (12.5%)		3/17 (17.6%)		3/22 (13.6%)		0/1 (0%)		0/8 (0%)		10/89 (11.2%)		7/85 (8.2%)
Dizziness	0/16 (0%)		1/17 (5.9%)		1/22 (4.5%)		0/1 (0%)		1/8 (12.5%)		0/89 (0%)		0/85 (0%)
Paraesthesia	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		0/89 (0%)		0/85 (0%)
Psychiatric disorders
Anxiety	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Insomnia	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		1/8 (12.5%)		6/89 (6.7%)		1/85 (1.2%)
Reproductive system and breast disorders
Vaginal discharge	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/16 (6.3%)		1/17 (5.9%)		3/22 (13.6%)		0/1 (0%)		0/8 (0%)		9/89 (10.1%)		13/85 (15.3%)
Dyspnoea	1/16 (6.3%)		3/17 (17.6%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		7/89 (7.9%)		3/85 (3.5%)
Oropharyngeal pain	1/16 (6.3%)		1/17 (5.9%)		1/22 (4.5%)		0/1 (0%)		0/8 (0%)		3/89 (3.4%)		7/85 (8.2%)
Rhinorrhoea	0/16 (0%)		1/17 (5.9%)		1/22 (4.5%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Bronchospasm	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Dysphonia	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Dyspnoea exertional	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Catarrh	0/16 (0%)		0/17 (0%)		2/22 (9.1%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Skin and subcutaneous tissue disorders
Erythema	1/16 (6.3%)		0/17 (0%)		2/22 (9.1%)		0/1 (0%)		0/8 (0%)		6/89 (6.7%)		14/85 (16.5%)
Hyperhidrosis	1/16 (6.3%)		2/17 (11.8%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Pruritus	0/16 (0%)		1/17 (5.9%)		2/22 (9.1%)		0/1 (0%)		0/8 (0%)		4/89 (4.5%)		8/85 (9.4%)
Rash	0/16 (0%)		2/17 (11.8%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		10/89 (11.2%)		10/85 (11.8%)
Panniculitis	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Pityriasis	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Rash erythematous	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Rash pruritic	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Skin lesion	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Urticaria	0/16 (0%)		1/17 (5.9%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Vascular disorders
Hypotension	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		6/89 (6.7%)		1/85 (1.2%)
Thrombophlebitis	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Hot Flush	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Peripheral Venous Disease	1/16 (6.3%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		0/89 (0%)		0/85 (0%)
Hypertension	0/16 (0%)		0/17 (0%)		0/22 (0%)		0/1 (0%)		0/8 (0%)		5/89 (5.6%)		0/85 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

Name/Title	Medical Communications
Organization	Hoffmann- LaRoche
Phone	1-800-821-8590
Email	genentech@druginfo.com

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01292603

Other Study ID Numbers:

BO25341
2010-021380-32

First Posted:

Feb 9, 2011

Last Update Posted:

Dec 19, 2018

Last Verified:

Nov 1, 2018