A Study of MabThera (Rituximab) Plus Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia.
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT00738374
Collaborator
(none)
97
20
1
50.4
4.9
0.1
Study Details
Study Description
Brief Summary
This single arm study will assess the efficacy and safety of MabThera + chlorambucil as induction therapy, followed in responders by maintenance therapy or observation in elderly patients with previously untreated chronic lymphocytic leukemia. During the induction phase patients will receive 2 x 4 weekly courses of chlorambucil followed by 8 x 4 weekly courses of chlorambucil + MabThera. Subsequently, responders will be randomized to receive 12 doses of MabThera given every 8 weeks, or no further treatment. The anticipated time on study treatment is 2+ years, and the target sample size is <100 individuals.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
97 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Study of Chlorambucil Plus MabThera as Induction Therapy Followed in Responders by Maintenance Therapy Versus Observation on Response Rate in Patients >=60 Years With Previously Untreated Chronic Lymphocytic Leukemia
Actual Study Start Date
:
Nov 3, 2008
Actual Primary Completion Date
:
Jan 14, 2013
Actual Study Completion Date
:
Jan 14, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1
|
Drug: rituximab [MabThera/Rituxan]
375mg/m2 iv on day 1 of course 3; 500mg/m2 iv on day 1 of courses 4-8 (induction phase); 375mg/m2 iv every 8 weeks (maintenance phase).
Drug: chlorambucil
8mg/m2 po on days 1-7 of courses 1-8
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Documented CR, CRi, or PR at the End of Induction Treatment [Month 10]
CR defined as: 1) laboratory CR: peripheral blood lymphocytes (PBL) less than (<) 4000/microliter (μL), neutrophils (PMN) greater than (>) 1500/μL, platelets >100,000/μL, and hemoglobin (Hb) >11 grams per deciliter (g/dL); 2) clinical CR: lymph nodes (LN) <1.5 centimeter (cm), and no constitutional symptoms, hepatomegaly (HM) or splenomegaly (SM); 3) instrumental CR: LN <1.5 cm and no HM/SM, and 4) bone marrow (BM) CR: normocellular aspirate/biopsy for participant age <30 percent (%) lymphocytes, and no B cell lymphoid nodules. CRi was defined as CR with anemia, thrombocytopenia, or neutropenia not related to chronic lymphocytic leukemia (CLL), with no clonal infiltrate in aspirate or biopsy. PR defined as: a 50% decrease in PBL, a 50% decrease in LN size, no increase in LN size, no new enlarged LN, a 50% reduction from baseline (BL) in the HM/SM, and 1 of the following: PMN >1500/μL, platelets >100,000/μL or >50% improvement from BL, and Hb >11.0 g/dL or >50% improvement from BL.
Secondary Outcome Measures
- Percentage of Participants With Documented CR, CRi, or PR at the End of Study [Month 35]
CR defined as: 1) laboratory CR: PBL <4000/μL, PMN > 1500/μL, platelets > 100,000/μL, and Hb > 11 g/dL; 2) clinical CR: LN < 1.5 cm, and no constitutional symptoms, HM or SM; 3) instrumental CR: LN < 1.5 cm and no HM/SM, and 4) bone marrow CR: normocellular aspirate/biopsy for participant age < 30% lymphocytes, and no B cell lymphoid nodules. CRi was defined as CR with anemia, thrombocytopenia, or neutropenia not related to CLL, with no clonal infiltrate in aspirate or biopsy. PR defined as: a 50% decrease in PBL, a 50% decrease in LN size, no increase in LN size, no new enlarged LN, a 50% reduction from BL in the HM/SM, and 1 of the following: PMN > 1500/μL, platelets > 100,000/μL or > 50% improvement from BL, and Hb >11.0 g/dL or > 50% improvement from BL.
- Percentage of Participants With CR, CRi, PR, Stable Disease (SD), Progressive Disease (PD), Relapse, or Nodular PR at the End of Induction Treatment [Month 10]
CR, CRi, and PR as previously defined. PD was defined by 1 of the following: 1) lymphadenopathy: any new lesion, HM/SM, or other organ infiltrates, or a greater than or equal to (≥) 50% increase in greatest diameter of any previously noted lesion; 2) a ≥ 50% increase in previously noted HM/SM, or new appearance of HM/SM; 3) a ≥ 50% increase in blood lymphocyte count with at least 5000 B lymphocytes/μL; 4) transformation to a more aggressive histology, e.g., Richter's syndrome; or 5) occurrence of cytopenia attributable to CLL. SD was defined by the absence of necessary criteria to achieve CR or PR, but no advancement to PD. Relapse was defined by a previously noted CR or PR with advancement to PD after a period of ≥ 6 months. Nodular PR was defined by the presence of residual lymphoid nodules.
- Percentage of Participants With CR, PR, SD, PD, Relapse, or Nodular PR at the End of Study [Month 35]
CR, and PR as previously defined. PD was defined by 1 of the following: 1) lymphadenopathy: any new lesion, HM/SM, or other organ infiltrates, or a ≥ 50% increase in greatest diameter of any previously noted lesion; 2) a ≥50% increase in previously noted HM/SM, or new appearance of HM/SM; 3) a ≥50% increase in blood lymphocyte count with at least 5000 B lymphocytes/μL; 4) transformation to a more aggressive histology, e.g., Richter's syndrome; or 5) occurrence of cytopenia attributable to CLL. SD was defined by the absence of necessary criteria to achieve CR or PR, but no advancement to PD. Relapse was defined by a previously noted CR or PR with advancement to PD after a period of ≥6 months. Nodular PR was defined by the presence of residual lymphoid nodules.
- Number of Participants With Immunophenotypic CR - BM, Immunophenotypic CR - Peripheral Blood (PB), Molecular CR - BM, or Molecular CR - PB at the End of Induction Treatment [Month 10]
Immunophenotypic CR was defined as the absence of minimal residual disease (MRD) evaluated in participants with CR by 4-color flow cytometry of PB and BM B cells to confirm that tissue was comprised of non-CLL cells. Molecular CR was defined as the absence of MRD evaluated in participants with CR by quantitative polymerase chain reaction (PCR) in PB and BM B cells to confirm that tissue was comprised of non-CLL cells.
- Percentage of Participants With CR, CRi, PR, SD, PD, or Relapse at the End of Study [Month 35]
CR, CRi, PR, SD, PD, relapse, and nodular PR as previously defined.
- Percentage of Participants With Immunophenotypic CR - BM or Immunophenotypic CR - PB at the End of Study [Month 35]
Immunophenotypic CR was defined as the absence of MRD evaluated in participants who achieved CR by 4-color flow cytometry of PB and BM B cells to confirm that tissue was comprised of non-CLL cells.
- Percentage of Participants With Molecular CR - BM or Molecular CR - PB at the End of Study [Month 35]
Molecular CR was defined as the absence of MRD evaluated in participants who achieved CR by quantitative PCR in PB and BM B cells to confirm that tissue was comprised of non-CLL cells.
- Number of Participants With Disease Progression, Relapse, Death, Withdrawal Because of an Adverse Event (AE), or New CLL Treatment [Screening, Days 1 and 15 of Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.]
Event-free Survival (EFS) was defined as the time from the first dose of study treatment to the date of first documentation of disease progression, relapse for participants with previous CR, death due to any cause, withdrawal due to AE, or beginning new CLL treatment. CR and PD as previously defined. Participants were censored at the time of data cut-off to the most recent date of disease assessment. Participants without a post-BL disease assessment were censored at the time of first dose of study treatment.
- EFS [Screening, Days 1 and 15 of Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.]
The median time, in days, from the the date of first dose of study treatment to the date of first documentation of disease progression, relapse for participants with CR, death due to any cause, withdrawal due to AE, or new CLL treatment. CR and PD as previously defined. Participants were censored at the time of data cut-off to the most recent date of disease assessment. Participants without a post-BL disease assessment were censored at the time of first dose if study treatment. The 95% CI was determined using Kaplan-Meier methodology.
- Number of Participants With Disease Progression or Death [Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.]
Progression-free survival (PFS) was defined as the time from the first dose of study treatment to the first documentation of disease progression or death. PD as previously defined. Participants who were withdrawn from the study without documented disease progression were censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without a post-BL tumor assessment, but known to be alive, were censored at the time of the first dose of study treatment.
- PFS [Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.]
The median time, in days, from the date of the first dose of study treatment to the date of first documentation of disease progression or death. CR and PD as previously defined. Participants who were withdrawn from the study without documented disease progression were censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without a post-BL tumor assessment, but known to be alive, were censored at the time of the first dose of study treatment. The 95% CI was determined using Kaplan-Meier methodology.
- Number of Participants With New CLL Treatment or Death [Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.]
Time to new CLL treatment (TTNT) was defined as the time from the first dose of study treatment to the date of new CLL treatment received or the date of death from any cause. Participants who did not receive new CLL treatment and were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without a follow-up assessment were censored at the day of last dose of study treatment.
- Time to Next Treatment (TTNT) [Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.]
The mean time, in days, from the date of the first dose of study treatment to the date of new CLL treatment or the date of death from any cause. Participants who did not receive new CLL treatment and were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without a follow-up assessment were censored at the day of last dose of study treatment. Mean survival time and it's standard error (SE) were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
- Number of Participants Who Died [Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.]
Overall Survival (OS) was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. Participants were censored at the date of the last follow-up assessment. Participants without a follow-up assessment were censored at the day of last dose of study treatment.
- OS [Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.]
The mean time, in days, from the date of the first dose of study treatment to the date of death due to any cause. Participants were censored at the date of the last follow-up assessment. Participants without a follow-up assessment were censored at the day of last dose of study treatment. The mean survival time and it's SE were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
- Number of Participants With PD or Death After a Confirmed CR, CRi, or PR [Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.]
Duration of response was defined as the time from the date of the first documented CR, CRi, or PR to the date of disease progression or death. CR, CRi, PR, and PD as previously defined. Participants with no documented PD after CR, CRi, or PR were censored at the last date at which they were known to have had CR, CRi, or PR, respectively.
- Duration of Response [Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.]
The mean time, in days, from the date of first documented CR, CRi or PR to the date disease progression or death. CR, CRi, PR, and PD as previously defined. Participants with no documented PD after CR, CRi, or PR were censored at the last date at which they were known to have had CR, CRi, or PR, respectively.
- Number of Participants With PD or Death After a Confirmed CR/CRi [Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.]
Disease-free survival was defined at the time from the date of first documented CR or CRi to the date of disease progression or death. CR, CRi, and PD as previously defined. Participants with no documented PD after CR or CRi were censored on the last date at which they were known to have had CR or CRi.
- Disease-Free Survival [Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months.]
The mean time, in days, from the date of first documented CR or CRi to the date of disease progression or death. CR, CRi, and PD as previously defined. Participants with no documented PD after CR or CRi were censored on the last date at which they were known to have had CR or CRi. In both groups, the mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
Eligibility Criteria
Criteria
Ages Eligible for Study:
60 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
adult patients, >=60 years of age;
-
CD20+ chronic lymphocytic leukemia (CLL);
-
no previous treatment for CLL;
-
ECOG performance status 0-1.
Exclusion Criteria:
-
co-morbid conditions requiring long term use of systemic corticosteroids during study treatment;
-
history of severe cardiac disease;
-
transformation to aggressive B-cell malignancy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Az. Osp. Pugliese; Dh Oncologico | Catanzaro | Calabria | Italy | 88100 |
| 2 | P.O. Annunziata; U.O. Ematologia | Cosenza | Calabria | Italy | 87100 |
| 3 | Ospedale Riuniti; Divisione Di Ematologia | Reggio Calabria | Calabria | Italy | 89100 |
| 4 | Ospedale Cardarelli; Divisione Di Ematologia | Napoli | Campania | Italy | 80131 |
| 5 | A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna | Bologna | Emilia-Romagna | Italy | 40138 |
| 6 | Arcispedale S. Anna; Sezione Di Ematologia | Ferrara | Emilia-Romagna | Italy | 44100 |
| 7 | Ospedale S. Eugenio; Divisione Di Ematologia | Roma | Lazio | Italy | 00144 |
| 8 | Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA | Roma | Lazio | Italy | 00161 |
| 9 | Uni Degli Studi Di Genova; 1A Divisione Di Ematologia | Genova | Liguria | Italy | 16132 |
| 10 | Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora | Milano | Lombardia | Italy | 20122 |
| 11 | Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia | Milano | Lombardia | Italy | 20162 |
| 12 | A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia | Torino | Piemonte | Italy | 10126 |
| 13 | Ospedale Molinette - Universita' Di Torino; Cliniche Universitarie Ematologia I | Torino | Piemonte | Italy | 10126 |
| 14 | Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica | Bari | Puglia | Italy | 70124 |
| 15 | Az. Osp. Papardo; Struttura Complessa Di Ematologia | Messina | Sicilia | Italy | 98165 |
| 16 | Ospedale Ferrarotto; Divisione Di Ematologia | Via S. Sofia 78 | Sicilia | Italy | 95123 |
| 17 | Az. Osp. Di Careggi; Divisione Di Ematologia | Firenze | Toscana | Italy | 50135 |
| 18 | A.O. Universitaria Senese; Ematologia | Siena | Toscana | Italy | 53100 |
| 19 | Uni Degli Studi; Dip.Med.Clinica E Sperim. Ematologia | Padova | Veneto | Italy | 35128 |
| 20 | Policlinico G. B. Rossi; Divisione Di Ematologia | Verona | Veneto | Italy | 37134 |
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:
NCT00738374
Other Study ID Numbers:
- ML21445
- 2008-001612-20
First Posted:
Aug 20, 2008
Last Update Posted:
Aug 15, 2017
Last Verified:
Jun 1, 2017
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Chlorambucil (CLB) Plus (+) Rituximab (R): Induction Treatment | CLB + R: Completed Induction Treament But Not Randomized | CLB + R: Maintenance Treatment | CLB + R: Observation |
|---|---|---|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 milligrams per square meter (mg/m^2), orally (PO) as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, intravenously (IV), on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with complete response (CR), complete response with incomplete bone marrow recovery (CRi), or partial response (PR) were randomized to receive either rituximab, 375 mg/m^2, IV, every 8 weeks for up to 24 months, or to be observed for up to 24 months with no further treatment. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants were not randomized to receive further treatment or observation. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive rituximab, 375 mg/m^2, IV, once every 8 weeks for a total of 12 infusions for up to 24 months. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to be observed for up to 24 months and received no further treatment. |
| Period Title: Induction Treatment Phase | ||||
| STARTED | 97 | 0 | 0 | 0 |
| COMPLETED | 73 | 0 | 0 | 0 |
| NOT COMPLETED | 24 | 0 | 0 | 0 |
| Period Title: Induction Treatment Phase | ||||
| STARTED | 0 | 7 | 34 | 32 |
| COMPLETED | 0 | 0 | 27 | 20 |
| NOT COMPLETED | 0 | 7 | 7 | 12 |
Baseline Characteristics
| Arm/Group Title | CLB + R: Not Randomized | CLB + R: Maintenance Treatment | CLB + R: Observation | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants began a 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants who completed the induction treatment with CR, CRi, or PR were randomized to receive either rituximab, 375 mg/m^2, IV, every 8 weeks for up to 24 months, or to be observed for up to 24 months with no further treatment. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive rituximab, 375 mg/m^2, IV, once every 8 weeks for a total of 12 infusions for up to 24 months. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to be observed for up to 24 months and received no further treatment. | Total of all reporting groups |
| Overall Participants | 31 | 34 | 32 | 97 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
74.7
(6.5)
|
69.8
(5.4)
|
70.2
(5.1)
|
71.7
(6.1)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
13
41.9%
|
10
29.4%
|
9
28.1%
|
32
33%
|
| Male |
18
58.1%
|
24
70.6%
|
23
71.9%
|
65
67%
|
Outcome Measures
| Title | Percentage of Participants With Documented CR, CRi, or PR at the End of Induction Treatment |
|---|---|
| Description | CR defined as: 1) laboratory CR: peripheral blood lymphocytes (PBL) less than (<) 4000/microliter (μL), neutrophils (PMN) greater than (>) 1500/μL, platelets >100,000/μL, and hemoglobin (Hb) >11 grams per deciliter (g/dL); 2) clinical CR: lymph nodes (LN) <1.5 centimeter (cm), and no constitutional symptoms, hepatomegaly (HM) or splenomegaly (SM); 3) instrumental CR: LN <1.5 cm and no HM/SM, and 4) bone marrow (BM) CR: normocellular aspirate/biopsy for participant age <30 percent (%) lymphocytes, and no B cell lymphoid nodules. CRi was defined as CR with anemia, thrombocytopenia, or neutropenia not related to chronic lymphocytic leukemia (CLL), with no clonal infiltrate in aspirate or biopsy. PR defined as: a 50% decrease in PBL, a 50% decrease in LN size, no increase in LN size, no new enlarged LN, a 50% reduction from baseline (BL) in the HM/SM, and 1 of the following: PMN >1500/μL, platelets >100,000/μL or >50% improvement from BL, and Hb >11.0 g/dL or >50% improvement from BL. |
| Time Frame | Month 10 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat (ITT) population: all consented participants who received at least 1 dose of rituximab. |
| Arm/Group Title | CLB + R: All Participants |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive either rituximab, 375 mg/m^2, IV, once every 8 weeks for up to 24 months (up to 12 infusions), or to be observed for up to 24 months with no further treatment. |
| Measure Participants | 85 |
| Number (95% Confidence Interval) [percentage of participants] |
82.4
265.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CLB + R: All Participants |
|---|---|---|
| Comments | Analysis compared responders and non-responders. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0008 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Title | Percentage of Participants With Documented CR, CRi, or PR at the End of Study |
|---|---|
| Description | CR defined as: 1) laboratory CR: PBL <4000/μL, PMN > 1500/μL, platelets > 100,000/μL, and Hb > 11 g/dL; 2) clinical CR: LN < 1.5 cm, and no constitutional symptoms, HM or SM; 3) instrumental CR: LN < 1.5 cm and no HM/SM, and 4) bone marrow CR: normocellular aspirate/biopsy for participant age < 30% lymphocytes, and no B cell lymphoid nodules. CRi was defined as CR with anemia, thrombocytopenia, or neutropenia not related to CLL, with no clonal infiltrate in aspirate or biopsy. PR defined as: a 50% decrease in PBL, a 50% decrease in LN size, no increase in LN size, no new enlarged LN, a 50% reduction from BL in the HM/SM, and 1 of the following: PMN > 1500/μL, platelets > 100,000/μL or > 50% improvement from BL, and Hb >11.0 g/dL or > 50% improvement from BL. |
| Time Frame | Month 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. |
| Arm/Group Title | CLB + R: Maintenance Treatment | CLB + R: Observation |
|---|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive rituximab, 375 mg/m^2, IV, once every 8 weeks for a total of 12 infusions for up to 24 months. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to be observed for up to 24 months and received no further treatment. |
| Measure Participants | 34 | 32 |
| Number (95% Confidence Interval) [percentage of participants] |
55.9
180.3%
|
34.4
101.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CLB + R: All Participants, CLB + R: Observation |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0795 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Title | Percentage of Participants With CR, CRi, PR, Stable Disease (SD), Progressive Disease (PD), Relapse, or Nodular PR at the End of Induction Treatment |
|---|---|
| Description | CR, CRi, and PR as previously defined. PD was defined by 1 of the following: 1) lymphadenopathy: any new lesion, HM/SM, or other organ infiltrates, or a greater than or equal to (≥) 50% increase in greatest diameter of any previously noted lesion; 2) a ≥ 50% increase in previously noted HM/SM, or new appearance of HM/SM; 3) a ≥ 50% increase in blood lymphocyte count with at least 5000 B lymphocytes/μL; 4) transformation to a more aggressive histology, e.g., Richter's syndrome; or 5) occurrence of cytopenia attributable to CLL. SD was defined by the absence of necessary criteria to achieve CR or PR, but no advancement to PD. Relapse was defined by a previously noted CR or PR with advancement to PD after a period of ≥ 6 months. Nodular PR was defined by the presence of residual lymphoid nodules. |
| Time Frame | Month 10 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | CLB + R: Induction Treatment |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. |
| Measure Participants | 85 |
| CR |
16.5
53.2%
|
| CRi |
2.4
7.7%
|
| PR |
60.0
193.5%
|
| SD |
4.7
15.2%
|
| PD |
3.5
11.3%
|
| Relapse |
0.0
0%
|
| Nodular PR |
3.5
11.3%
|
| Unknown |
9.4
30.3%
|
| Title | Percentage of Participants With CR, PR, SD, PD, Relapse, or Nodular PR at the End of Study |
|---|---|
| Description | CR, and PR as previously defined. PD was defined by 1 of the following: 1) lymphadenopathy: any new lesion, HM/SM, or other organ infiltrates, or a ≥ 50% increase in greatest diameter of any previously noted lesion; 2) a ≥50% increase in previously noted HM/SM, or new appearance of HM/SM; 3) a ≥50% increase in blood lymphocyte count with at least 5000 B lymphocytes/μL; 4) transformation to a more aggressive histology, e.g., Richter's syndrome; or 5) occurrence of cytopenia attributable to CLL. SD was defined by the absence of necessary criteria to achieve CR or PR, but no advancement to PD. Relapse was defined by a previously noted CR or PR with advancement to PD after a period of ≥6 months. Nodular PR was defined by the presence of residual lymphoid nodules. |
| Time Frame | Month 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who were assessed at Month 35 were included in the analysis. |
| Arm/Group Title | CLB + R: Maintenance Treatment | CLB + R: Observation |
|---|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive rituximab, 375 mg/m^2, IV, once every 8 weeks for a total of 12 infusions for up to 24 months. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to be observed for up to 24 months and received no further treatment. |
| Measure Participants | 31 | 28 |
| CR |
32.3
104.2%
|
21.4
62.9%
|
| PR |
29.0
93.5%
|
14.3
42.1%
|
| SD |
3.2
10.3%
|
7.1
20.9%
|
| PD |
29.0
93.5%
|
39.3
115.6%
|
| Relapse |
6.5
21%
|
14.3
42.1%
|
| Nodular PR |
0.0
0%
|
3.6
10.6%
|
| Title | Number of Participants With Immunophenotypic CR - BM, Immunophenotypic CR - Peripheral Blood (PB), Molecular CR - BM, or Molecular CR - PB at the End of Induction Treatment |
|---|---|
| Description | Immunophenotypic CR was defined as the absence of minimal residual disease (MRD) evaluated in participants with CR by 4-color flow cytometry of PB and BM B cells to confirm that tissue was comprised of non-CLL cells. Molecular CR was defined as the absence of MRD evaluated in participants with CR by quantitative polymerase chain reaction (PCR) in PB and BM B cells to confirm that tissue was comprised of non-CLL cells. |
| Time Frame | Month 10 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | CLB + R: Induction Treatment |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. |
| Measure Participants | 85 |
| Immunophenotypic CR - BM |
2
6.5%
|
| Immunophenotypic CR - PB |
3
9.7%
|
| Molecular CR - BM |
0
0%
|
| Molecular CR - PB |
0
0%
|
| Title | Percentage of Participants With CR, CRi, PR, SD, PD, or Relapse at the End of Study |
|---|---|
| Description | CR, CRi, PR, SD, PD, relapse, and nodular PR as previously defined. |
| Time Frame | Month 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. |
| Arm/Group Title | CLB + R: Maintenance Treatment | CLB + R: Observation |
|---|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive rituximab, 375 mg/m^2, IV, once every 8 weeks for a total of 12 infusions for up to 24 months. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to be observed for up to 24 months and received no further treatment. |
| Measure Participants | 34 | 32 |
| CR |
29.4
94.8%
|
18.7
55%
|
| CRi |
0.0
0%
|
0.0
0%
|
| PR |
26.4
85.2%
|
12.5
36.8%
|
| Title | Percentage of Participants With Immunophenotypic CR - BM or Immunophenotypic CR - PB at the End of Study |
|---|---|
| Description | Immunophenotypic CR was defined as the absence of MRD evaluated in participants who achieved CR by 4-color flow cytometry of PB and BM B cells to confirm that tissue was comprised of non-CLL cells. |
| Time Frame | Month 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants, only participants with a confirmed CR were included in the analysis. |
| Arm/Group Title | CLB + R: Maintenance Treatment |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive rituximab, 375 mg/m^2, IV, once every 8 weeks for a total of 12 infusions for up to 24 months. |
| Measure Participants | 10 |
| Immunophenotypic CR - BM |
10.0
32.3%
|
| Immunophenotypic CR - PB |
30.0
96.8%
|
| Title | Percentage of Participants With Molecular CR - BM or Molecular CR - PB at the End of Study |
|---|---|
| Description | Molecular CR was defined as the absence of MRD evaluated in participants who achieved CR by quantitative PCR in PB and BM B cells to confirm that tissue was comprised of non-CLL cells. |
| Time Frame | Month 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants analyzed for the given parameter at the specified timepoint. |
| Arm/Group Title | CLB + R: Maintenance Treatment |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive rituximab, 375 mg/m^2, IV, once every 8 weeks for a total of 12 infusions for up to 24 months. |
| Measure Participants | 3 |
| Molecular CR - BM |
100.0
322.6%
|
| Molecular CR - PB |
33.3
107.4%
|
| Title | Number of Participants With Disease Progression, Relapse, Death, Withdrawal Because of an Adverse Event (AE), or New CLL Treatment |
|---|---|
| Description | Event-free Survival (EFS) was defined as the time from the first dose of study treatment to the date of first documentation of disease progression, relapse for participants with previous CR, death due to any cause, withdrawal due to AE, or beginning new CLL treatment. CR and PD as previously defined. Participants were censored at the time of data cut-off to the most recent date of disease assessment. Participants without a post-BL disease assessment were censored at the time of first dose of study treatment. |
| Time Frame | Screening, Days 1 and 15 of Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | CLB + R: All Participants |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive either rituximab, 375 mg/m^2, IV, once every 8 weeks for up to 24 months (up to 12 infusions), or to be observed for up to 24 months with no further treatment. |
| Measure Participants | 85 |
| Number [participants] |
43
138.7%
|
| Title | EFS |
|---|---|
| Description | The median time, in days, from the the date of first dose of study treatment to the date of first documentation of disease progression, relapse for participants with CR, death due to any cause, withdrawal due to AE, or new CLL treatment. CR and PD as previously defined. Participants were censored at the time of data cut-off to the most recent date of disease assessment. Participants without a post-BL disease assessment were censored at the time of first dose if study treatment. The 95% CI was determined using Kaplan-Meier methodology. |
| Time Frame | Screening, Days 1 and 15 of Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | CLB + R: All Participants |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive either rituximab, 375 mg/m^2, IV, once every 8 weeks for up to 24 months (up to 12 infusions), or to be observed for up to 24 months with no further treatment. |
| Measure Participants | 85 |
| Median (95% Confidence Interval) [days] |
1051
|
| Title | Number of Participants With Disease Progression or Death |
|---|---|
| Description | Progression-free survival (PFS) was defined as the time from the first dose of study treatment to the first documentation of disease progression or death. PD as previously defined. Participants who were withdrawn from the study without documented disease progression were censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without a post-BL tumor assessment, but known to be alive, were censored at the time of the first dose of study treatment. |
| Time Frame | Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | CLB + R: All Participants |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive either rituximab, 375 mg/m^2, IV, once every 8 weeks for up to 24 months (up to 12 infusions), or to be observed for up to 24 months with no further treatment. |
| Measure Participants | 85 |
| Number [participants] |
35
112.9%
|
| Title | PFS |
|---|---|
| Description | The median time, in days, from the date of the first dose of study treatment to the date of first documentation of disease progression or death. CR and PD as previously defined. Participants who were withdrawn from the study without documented disease progression were censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without a post-BL tumor assessment, but known to be alive, were censored at the time of the first dose of study treatment. The 95% CI was determined using Kaplan-Meier methodology. |
| Time Frame | Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | CLB + R: All Participants |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive either rituximab, 375 mg/m^2, IV, once every 8 weeks for up to 24 months (up to 12 infusions), or to be observed for up to 24 months with no further treatment. |
| Measure Participants | 85 |
| Median (95% Confidence Interval) [days] |
1059
|
| Title | Number of Participants With New CLL Treatment or Death |
|---|---|
| Description | Time to new CLL treatment (TTNT) was defined as the time from the first dose of study treatment to the date of new CLL treatment received or the date of death from any cause. Participants who did not receive new CLL treatment and were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without a follow-up assessment were censored at the day of last dose of study treatment. |
| Time Frame | Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | CLB + R: All Participants |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive either rituximab, 375 mg/m^2, IV, once every 8 weeks for up to 24 months (up to 12 infusions), or to be observed for up to 24 months with no further treatment. |
| Measure Participants | 85 |
| Number [participants] |
22
71%
|
| Title | Time to Next Treatment (TTNT) |
|---|---|
| Description | The mean time, in days, from the date of the first dose of study treatment to the date of new CLL treatment or the date of death from any cause. Participants who did not receive new CLL treatment and were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without a follow-up assessment were censored at the day of last dose of study treatment. Mean survival time and it's standard error (SE) were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. |
| Time Frame | Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | CLB + R: All Participants |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive either rituximab, 375 mg/m^2, IV, once every 8 weeks for up to 24 months (up to 12 infusions), or to be observed for up to 24 months with no further treatment. |
| Measure Participants | 85 |
| Mean (Standard Error) [days] |
1048.19
(31.86)
|
| Title | Number of Participants Who Died |
|---|---|
| Description | Overall Survival (OS) was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. Participants were censored at the date of the last follow-up assessment. Participants without a follow-up assessment were censored at the day of last dose of study treatment. |
| Time Frame | Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | CLB + R: All Participants |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive either rituximab, 375 mg/m^2, IV, once every 8 weeks for up to 24 months (up to 12 infusions), or to be observed for up to 24 months with no further treatment. |
| Measure Participants | 85 |
| Number [participants] |
8
25.8%
|
| Title | OS |
|---|---|
| Description | The mean time, in days, from the date of the first dose of study treatment to the date of death due to any cause. Participants were censored at the date of the last follow-up assessment. Participants without a follow-up assessment were censored at the day of last dose of study treatment. The mean survival time and it's SE were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. |
| Time Frame | Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | CLB + R: All Participants |
|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive either rituximab, 375 mg/m^2, IV, once every 8 weeks for up to 24 months (up to 12 infusions), or to be observed for up to 24 months with no further treatment. |
| Measure Participants | 85 |
| Mean (Standard Error) [days] |
1135.04
(24.25)
|
| Title | Number of Participants With PD or Death After a Confirmed CR, CRi, or PR |
|---|---|
| Description | Duration of response was defined as the time from the date of the first documented CR, CRi, or PR to the date of disease progression or death. CR, CRi, PR, and PD as previously defined. Participants with no documented PD after CR, CRi, or PR were censored at the last date at which they were known to have had CR, CRi, or PR, respectively. |
| Time Frame | Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. |
| Arm/Group Title | CLB + R: Maintenance Treatment | CLB + R: Observation |
|---|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive rituximab, 375 mg/m^2, IV, once every 8 weeks for a total of 12 infusions for up to 24 months. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to be observed for up to 24 months and received no further treatment. |
| Measure Participants | 34 | 32 |
| Number [participants] |
11
35.5%
|
15
44.1%
|
| Title | Duration of Response |
|---|---|
| Description | The mean time, in days, from the date of first documented CR, CRi or PR to the date disease progression or death. CR, CRi, PR, and PD as previously defined. Participants with no documented PD after CR, CRi, or PR were censored at the last date at which they were known to have had CR, CRi, or PR, respectively. |
| Time Frame | Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. |
| Arm/Group Title | CLB + R: Maintenance Treatment | CLB + R: Observation |
|---|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive rituximab, 375 mg/m^2, IV, once every 8 weeks for a total of 12 infusions for up to 24 months. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to be observed for up to 24 months and received no further treatment. |
| Measure Participants | 34 | 32 |
| Mean (Standard Error) [days] |
840.87
(29.71)
|
747.82
(55.77)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CLB + R: All Participants, CLB + R: Observation |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2712 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Number of Participants With PD or Death After a Confirmed CR/CRi |
|---|---|
| Description | Disease-free survival was defined at the time from the date of first documented CR or CRi to the date of disease progression or death. CR, CRi, and PD as previously defined. Participants with no documented PD after CR or CRi were censored on the last date at which they were known to have had CR or CRi. |
| Time Frame | Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with a confirmed CR or CRi were included in the analysis. |
| Arm/Group Title | CLB + R: Maintenance Treatment | CLB + R: Observation |
|---|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive rituximab, 375 mg/m^2, IV, once every 8 weeks for a total of 12 infusions for up to 24 months. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to be observed for up to 24 months and received no further treatment. |
| Measure Participants | 16 | 15 |
| Number [participants] |
2
6.5%
|
8
23.5%
|
| Title | Disease-Free Survival |
|---|---|
| Description | The mean time, in days, from the date of first documented CR or CRi to the date of disease progression or death. CR, CRi, and PD as previously defined. Participants with no documented PD after CR or CRi were censored on the last date at which they were known to have had CR or CRi. In both groups, the mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. |
| Time Frame | Screening, Day 1 Courses 1-8 (4-week courses) and Day 1 of Courses 10-35 (4-week courses) for up to 35 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. |
| Arm/Group Title | CLB + R: Maintenance Treatment | CLB + R: Observation |
|---|---|---|
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive rituximab, 375 mg/m^2, IV, once every 8 weeks for a total of 12 infusions for up to 24 months. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to be observed for up to 24 months and received no further treatment. |
| Measure Participants | 34 | 32 |
| Mean (Standard Error) [days] |
699.91
(68.89)
|
732.28
(63.37)
|
Adverse Events
| Time Frame | Adverse events (AEs) were recorded from Screening through the Final Visit or withdrawal from study, approximately 35 months. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All participants who received at least 1 dose of chlorambucil or rituximab were included in the analysis. | |||||
| Arm/Group Title | CLB + R: Induction Treatment | CLB + R: Maintenance Treatment | CLB + R: Observation | |||
| Arm/Group Description | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive either rituximab, 375 mg/m^2, IV, once every 8 weeks for up to 24 months (up to 12 infusions), or to be observed for up to 24 months with no further treatment. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to receive rituximab, 375 mg/m^2, IV, once every 8 weeks for a total of 12 infusions for up to 24 months. | Participants completed an 8-month induction treatment phase where they received 8 (4-week) courses of treatment consisting of: CLB, 8 mg/m^2, PO as film-coated tablets, daily (dose could be divided in halves or thirds to prevent nausea), on Days 1-7 of Courses 1 and 2, Days 2-8 of Course 3, and Days 1-7 of Courses 4-8; and rituximab, 375 mg/m^2, IV, on Day 1 of Course 3, and 500 mg/m^2, IV, on Day 1 of Courses 4-8. Participants with CR, CRi, or PR were randomized to be observed for up to 24 months and received no further treatment. | |||
All Cause Mortality |
||||||
| CLB + R: Induction Treatment | CLB + R: Maintenance Treatment | CLB + R: Observation | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| CLB + R: Induction Treatment | CLB + R: Maintenance Treatment | CLB + R: Observation | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/97 (17.5%) | 4/34 (11.8%) | 4/32 (12.5%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 2/97 (2.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Haemorrhagic anaemia | 1/97 (1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Neutropenia | 1/97 (1%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Haemolytic anaemia | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Cardiac failure | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| General disorders | ||||||
| Death | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Pyrexia | 1/97 (1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Infections and infestations | ||||||
| Herpes zoster oticus | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Pneumonia | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Femur fracture | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Hand fracture | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Upper limb fracture | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Endometrial cancer | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Mixed oligo-astrocytoma | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Basal cell carcinoma | 0/97 (0%) | 1/34 (2.9%) | 1/32 (3.1%) | |||
| Porocarcinoma | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Squamous cell carcinoma of skin | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Nervous system disorders | ||||||
| Epilepsy | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Transient ischaemic attack | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pleural effusion | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash erythematous | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Toxic skin eruption | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| CLB + R: Induction Treatment | CLB + R: Maintenance Treatment | CLB + R: Observation | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 73/97 (75.3%) | 25/34 (73.5%) | 17/32 (53.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 14/97 (14.4%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Leukopenia | 5/97 (5.2%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Lymphadenopathy | 2/97 (2.1%) | 2/34 (5.9%) | 4/32 (12.5%) | |||
| Neutropenia | 31/97 (32%) | 5/34 (14.7%) | 1/32 (3.1%) | |||
| Splenomegaly | 1/97 (1%) | 0/34 (0%) | 2/32 (6.3%) | |||
| Thrombocytopenia | 16/97 (16.5%) | 1/34 (2.9%) | 1/32 (3.1%) | |||
| Lymphocytosis | 0/97 (0%) | 0/34 (0%) | 2/32 (6.3%) | |||
| Lymphopenia | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Haemolytic anaemia | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Cardiac disorders | ||||||
| Angina pectoris | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Atrial fibrillation | 1/97 (1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Hypertensive cardiomyopathy | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Sinus tachycardia | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Tachycardia | 1/97 (1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Ear and labyrinth disorders | ||||||
| Vertigo | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Hypoacusis | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Endocrine disorders | ||||||
| Thyroid disorder | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Thyroiditis | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal distension | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Abdominal pain | 3/97 (3.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Abdominal pain upper | 1/97 (1%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Constipation | 2/97 (2.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Diarrhoea | 4/97 (4.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Dyskinesia oesophageal | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Dyspepsia | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Hiatus hernia | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Nausea | 7/97 (7.2%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Reflux oesophagitis | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Vomiting | 4/97 (4.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Colitis | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Flatulence | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Gastritis | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Intestinal obstruction | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Tongue dry | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| General disorders | ||||||
| Asthenia | 4/97 (4.1%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Chest pain | 3/97 (3.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Chills | 2/97 (2.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Face oedema | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Fatigue | 5/97 (5.2%) | 0/34 (0%) | 3/32 (9.4%) | |||
| Hyperpyrexia | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Influenza like illness | 3/97 (3.1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Infusion related reaction | 6/97 (6.2%) | 0/34 (0%) | 0/32 (0%) | |||
| Mucosal inflammation | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Oedema peripheral | 2/97 (2.1%) | 2/34 (5.9%) | 0/32 (0%) | |||
| Pyrexia | 11/97 (11.3%) | 0/34 (0%) | 2/32 (6.3%) | |||
| Cyst | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Pain | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Hepatobiliary disorders | ||||||
| Hepatomegaly | 1/97 (1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Immune system disorders | ||||||
| Hypersensitivity | 1/97 (1%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Multiple allergies | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Infections and infestations | ||||||
| Cellulitis | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Conjunctivitis bacterial | 1/97 (1%) | 2/34 (5.9%) | 0/32 (0%) | |||
| Cystitis | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Fungal infection | 2/97 (2.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Herpes simplex | 3/97 (3.1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Herpes zoster oticus | 1/97 (1%) | 1/34 (2.9%) | 2/32 (6.3%) | |||
| Nasopharyngitis | 2/97 (2.1%) | 1/34 (2.9%) | 1/32 (3.1%) | |||
| Pharyngitis | 2/97 (2.1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Productive cough | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Pyrexia | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Bronchitis | 0/97 (0%) | 4/34 (11.8%) | 1/32 (3.1%) | |||
| Gastroenteritis | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Hepatitis B | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Herpes zoster | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Pilonidal cyst | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Tooth abscess | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Arthropod bite | 1/97 (1%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Spinal compression fracture | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Humerus fracture | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Investigations | ||||||
| Breath sounds abnormal | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Platelet count decreased | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Transaminases increased | 1/97 (1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Blood creatine increased | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Blood lactate dehydrogenase increased | 0/97 (0%) | 2/34 (5.9%) | 0/32 (0%) | |||
| Weight decreased | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Metabolism and nutrition disorders | ||||||
| Anorexia | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Diabetes mellitus | 2/97 (2.1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Dyslipidaemia | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Hyperuricaemia | 1/97 (1%) | 1/34 (2.9%) | 2/32 (6.3%) | |||
| Decreased appetite | 0/97 (0%) | 0/34 (0%) | 2/32 (6.3%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 2/97 (2.1%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Back pain | 4/97 (4.1%) | 2/34 (5.9%) | 0/32 (0%) | |||
| Musculoskeletal pain | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Pain in extremity | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Bone pain | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Pain in jaw | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Nervous system disorders | ||||||
| Headache | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Memory impairment | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Neuropathy peripheral | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Syncope | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Dizziness | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Paraesthesia | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Renal and urinary disorders | ||||||
| Bladder disorder | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Dysuria | 1/97 (1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Micturition urgency | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Reproductive system and breast disorders | ||||||
| Benign prostatic hyperplasia | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Gynaecomastia | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Peyronie's disease | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 5/97 (5.2%) | 3/34 (8.8%) | 1/32 (3.1%) | |||
| Dyspnoea | 3/97 (3.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Nasal septum perforation | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Oropharyngeal discomfort | 2/97 (2.1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Tonsillar hypertrophy | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Erythema | 2/97 (2.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Hyperhidrosis | 1/97 (1%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Pruritus | 5/97 (5.2%) | 0/34 (0%) | 0/32 (0%) | |||
| Rash | 2/97 (2.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Rash erythematous | 2/97 (2.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Skin lesion | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Night sweats | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Pemphigoid | 0/97 (0%) | 1/34 (2.9%) | 0/32 (0%) | |||
| Surgical and medical procedures | ||||||
| Haemorrhoid operation | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Knee operation | 0/97 (0%) | 0/34 (0%) | 1/32 (3.1%) | |||
| Vascular disorders | ||||||
| Deep vein thrombosis | 1/97 (1%) | 0/34 (0%) | 0/32 (0%) | |||
| Hypertension | 2/97 (2.1%) | 2/34 (5.9%) | 1/32 (3.1%) | |||
| Hypotension | 3/97 (3.1%) | 0/34 (0%) | 0/32 (0%) | |||
| Carotid artery stenosis | 0/97 (0%) | 1/34 (2.9%) | 1/32 (3.1%) | |||
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 | Hoffman-LaRoche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00738374
Other Study ID Numbers:
- ML21445
- 2008-001612-20
First Posted:
Aug 20, 2008
Last Update Posted:
Aug 15, 2017
Last Verified:
Jun 1, 2017