Trial Outcomes & Findings for A Study of MabThera (Rituximab) Plus Chlorambucil in Participants With Chronic Lymphocytic Leukemia. (NCT NCT00532129)
NCT ID: NCT00532129
Last Updated: 2016-04-06
Results Overview
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 56 days from the beginning of the last treatment cycle that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs as well as non-serious AEs.
COMPLETED
PHASE2
100 participants
First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
2016-04-06
Participant Flow
Participant milestones
| Measure |
Rituximab + Chlorambucil
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles (28 day cycles). Participants who did not achieve complete response (CR) after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 milligrams per square meter per day (mg/m\^2/day) oral administration (PO) on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Treatment Period
STARTED
|
100
|
|
Treatment Period
COMPLETED
|
51
|
|
Treatment Period
NOT COMPLETED
|
49
|
|
Follow-up Period
STARTED
|
98
|
|
Follow-up Period
COMPLETED
|
33
|
|
Follow-up Period
NOT COMPLETED
|
65
|
Reasons for withdrawal
| Measure |
Rituximab + Chlorambucil
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles (28 day cycles). Participants who did not achieve complete response (CR) after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 milligrams per square meter per day (mg/m\^2/day) oral administration (PO) on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Treatment Period
Adverse event/Serious adverse event
|
25
|
|
Treatment Period
Physician Decision
|
15
|
|
Treatment Period
Disease progression
|
3
|
|
Treatment Period
Protocol Violation
|
1
|
|
Treatment Period
Other
|
5
|
|
Follow-up Period
Adverse event/Serious adverse event
|
1
|
|
Follow-up Period
Disease progression
|
57
|
|
Follow-up Period
Lost to Follow-up
|
1
|
|
Follow-up Period
Other
|
6
|
Baseline Characteristics
A Study of MabThera (Rituximab) Plus Chlorambucil in Participants With Chronic Lymphocytic Leukemia.
Baseline characteristics by cohort
| Measure |
Rituximab + Chlorambucil
n=100 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Age, Continuous
|
69.5 years
STANDARD_DEVIATION 8.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
66 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)Population: FAS.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 56 days from the beginning of the last treatment cycle that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs as well as non-serious AEs.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=100 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Percentage of Participants With Treatment-Emergent Adverse Events (AEs)
|
99 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS.
Clinical CR was achieved if all of the following criteria were met: a)Absence of lymphadenopathy (LD) by physical examination (PE) and Computed Tomography (CT) scan (all lymph nodes less than \[\<\] 1.5 centimeters \[cm\] in diameter), b)No hepatomegaly (HM)/splenomegaly (SM) by PE/CT scan, c)Absence of B symptoms (unexplained fever greater than \[\>\] 38 degrees \[°\] Centigrade \[C\], drenching night sweats/\>10 percent \[%\] body weight loss in the last 6 months), d)Normal Complete Blood Count (CBC) (i. Leukocytes (Leuk) greater than or equal to \[≥\] 1.5×10\^9 per liter (/L), ii. Platelets (Plat) \>100×10\^9/L, and iii. Haemoglobin (Hb) \>11.0 grams per deciliter \[g/dL\]) and e)Once clinical, radiological and laboratory evaluations demonstrated CR, bone marrow (BM) biopsy and aspirate were performed 8 weeks later for confirmation; BM sample: normocellular for age, \<30% of the cells being lymphocytes (Lym) and lymphoid nodules (LN) absent was considered as a confirmed CR.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=100 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Percentage of Participants With Best Overall Response (BOR) of Clinical CR or Confirmed CR
Clinical CR
|
37.0 percentage of participants
|
|
Percentage of Participants With Best Overall Response (BOR) of Clinical CR or Confirmed CR
Confirmed CR
|
10.0 percentage of participants
|
|
Percentage of Participants With Best Overall Response (BOR) of Clinical CR or Confirmed CR
Clinical CR or Confirmed CR
|
47.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS.
PR was achieved if all of the following criteria were met: a)≥50% decrease in Lym count from the baseline value, b)≥50% reduction in LD by CT scan, c)≥50% reduction in size of liver/spleen by PE/CT scan and at least 1 of the following for a minimum of 8 weeks: i. Leuk ≥1.5×10\^9/L or 50% improvement over baseline, ii. Plat \>100×10\^9/L or 50% improvement over baseline and iii. Hb \>11.0 g/dL or 50% improvement over baseline without transfusion. Participants who fulfilled criteria for CR with persistent anemia/thrombocytopenia were considered in PRs. CR was achieved if all of the criteria were fulfilled for ≥8 weeks: a)Absence of LD by PE and CT scan, b)No HM/SM by PE/CT, c)Absence of B symptoms, d)Normal CBC, and e)BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=100 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Percentage of Participants With BOR of Partial Response (PR)
|
68.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS.
CR was achieved if all of the following criteria were met for ≥8 weeks: a)Absence of LD by PE and CT scan, b)No HM/SM by PE/CT scan, c)Absence of B symptoms, d)Normal CBC, and e)BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent. Participants with nPR were those who satisfied all of the CR criteria except for the BM, where LN could be identified histologically.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=100 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Percentage of Participants With BOR of Nodular Partial Response (nPR)
|
6.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS.
PD is considered if 1 of the following criteria is met: a)≥50% increase in sum of the products of ≥2 lymph nodes compared to their smallest size (at least one ≥2 cm in diameter) or appearance of new lymph nodes/extranodal lesions, b)≥50% increase in the size of hepatosplenomegaly (HSM) as determined by PE/CT scan; appearance of palpable HM/SM that was not previously present, c)≥50% increase in the absolute number of circulating Lym to ≥5×10\^9/L, d)Transformation to a more aggressive histology. Symptomatic deterioration (evident in clinical symptoms but not supported by tumor assessments), in such cases, the determination of clinical progression was based on symptomatic deterioration.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=100 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Percentage of Participants With BOR of Progressive Disease (PD)
|
4.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS.
Participants without CR/PR or PD were considered having a tumor response of SD. CR: a) Absence of LD by PE and CT, b) No HM/SM by PE/CT, c) Absence of B symptoms, d) Normal CBC, and e) BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent. PR: a) ≥50% decrease in Lym count from baseline, b) ≥50% reduction in LD, c) ≥50% reduction in size of liver/spleen by PE/CT and ≥1 of the following for at least 8 weeks: i. Leuk ≥1.5×10\^9/L or 50% improvement over baseline, ii. Plat \>100×10\^9/L or 50% improvement over baseline and iii. Hb \>11.0 g/dL or 50% improvement over baseline without transfusion. PD: a) ≥50% increase in sum of the products of ≥2 lymph nodes compared to their smallest size or appearance of new lymph nodes/extranodal lesions, or b) ≥50% increase in the size of HSM; new appearance of palpable HM/SM, or c) ≥50% increase in the absolute number of circulating Lym to ≥5×10\^9/L, or d) Transformation to a more aggressive histology.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=100 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Percentage of Participants With BOR of Stable Disease (SD)
|
11.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS.
Objective response was defined as a tumor response of CR or PR. CR was achieved if all of the criteria were met for ≥8 weeks: a)Absence of LD by PE and CT scan, b)No HM/SM by PE/CT scan, c)Absence of B symptoms, d)Normal CBC, and e)BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent. PR was achieved if all of the criteria were met: a)≥50% decrease in Lymp count from the baseline value, b)≥50% reduction in LD by CT scan, c)≥50% reduction in size of liver/spleen by PE/CT scan and at least 1 of the following for a minimum of 8 weeks: i. Leuk ≥1.5×10\^9/L or 50% improvement over baseline, ii. Plat \>100×10\^9/L or 50% improvement over baseline and iii. Hb \>11.0 g/dL or 50% improvement over baseline without transfusion. Participants who fulfilled criteria for CR with persistent anemia/thrombocytopenia were considered PRs.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=100 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Percentage of Participants With Objective Response (CR or PR)
|
84.0 percentage of participants
Interval 75.3 to 90.6
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS.
PD is considered if 1 of the following criteria is met: a)≥50% increase in sum of the products of ≥2 lymph nodes compared to their smallest size (at least one ≥2 cm in diameter) or appearance of new lymph nodes/extranodal lesions, b)≥50% increase in the size of HSM as determined by PE/CT scan; appearance of palpable HM/SM that was not previously present, c)≥50% increase in the absolute number of circulating Lym to ≥5×10\^9/L, d)Transformation to a more aggressive histology. Symptomatic deterioration (evident in clinical symptoms but not supported by tumor assessments), in such cases, the determination of clinical progression was based on symptomatic deterioration.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=100 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Percentage of Participant With Disease Progression or Death
|
68.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS.
PFS was defined as the interval (in days) from trial treatment start date to earlier of the date of first tumor response assessment of PD or date of death by any cause. Participants who experienced none of these events or who were lost to follow-up at the time of analysis were censored on last date when they were assessed for tumor response. PD is considered if 1 of the following criteria is met: a)≥50% increase in sum of products of ≥2 lymph nodes compared to their smallest size (at least one ≥2 cm in diameter) or appearance of new lymph nodes/extranodal lesions, b)≥50% increase in the size of HSM as determined by PE/CT; appearance of palpable HM/SM that was not previously present, c)≥50% increase in the number of circulating Lym to ≥5×10\^9/L, d)Transformation to a more aggressive histology. Symptomatic deterioration (evident in clinical symptoms but not supported by tumor assessments), in such cases, the determination of clinical progression was based on symptomatic deterioration.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=100 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Progression Free Survival (PFS) Time
|
716.5 days
Interval 500.0 to 784.0
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS population participants who achieved confirmed CR.
DFS time was defined as interval (in days) from first tumor response of CR to date of first tumor response of PD, or date of death by any cause. Participants who experienced none of these events or who were lost to follow-up at the time of analysis were censored on last date when they were assessed for tumor response. CR: a) Absence of LD by PE and CT, b) No HM/SM by PE/CT, c) Absence of B symptoms, d) Normal CBC, and e) BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent. PD: a) ≥50% increase in sum of the products of ≥2 lymph nodes compared to their smallest size or appearance of new lymph nodes/extranodal lesions, or b) ≥50% increase in the size of HSM; new appearance of palpable HM/SM, or c) ≥50% increase in the absolute number of circulating Lym to ≥5×10\^9/L, or d) Transformation to a more aggressive histology.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=10 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Disease Free Survival (DFS) Time
|
855.0 days
Interval 290.0 to 855.0
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS population participants who achieved confirmed CR, PR or nPR.
DoR: defined as interval (in days) from first tumor response (of CR/PR/nPR) to earlier of date of PD/death. Participants without PD/death or who were lost to follow-up were censored. CR: a)Absence of LD by PE and CT, b)No HM/SM by PE/CT, c)Absence of B symptoms, d)Normal CBC, and e)BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent. PR: a)≥50% decrease in Lym count from baseline value, b)≥50% reduction in LD, c)≥50% reduction in size of liver/spleen by PE/CT scan and d)Leuk, Plat and Hb ≥1.5×10\^9/L, \>100×10\^9/L and \>11.0 g/dL, respectively or 50% improvement (of all the 3) over baseline value. nPR: participants who satisfied all of CR criteria except for BM, where LN could be identified. PD: a)≥50% increase in sum of the products of ≥2 lymph nodes or appearance of new lymph nodes/extranodal lesions, or b)≥50% increase in size of HSM; new appearance of palpable HM/SM, or c)≥50% increase in number of Lym, or d)Transformation to a more aggressive histology.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=84 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Duration of Response (DoR)
|
645.0 days
Interval 561.0 to 758.0
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=100 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Percentage of Participants Who Died
|
15.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS.
This was defined as the interval (number of days) from the trial treatment start date to the date of death by any cause. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=100 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Overall Survival (OS) Time
|
NA percentage of participants
Median and 95% confidence interval of OS time not available due to insufficient follow-up to allow estimation.
|
SECONDARY outcome
Timeframe: Baseline until disease progression or death up to approximately 2.5 years (assessed at Baseline, Cycle 4 Day 1, Day 1 of Cycles 7-12, and thereafter every 3 months up to approximately 2.5 years; cycle length = 28 days)Population: FAS population participants who achieved confirmed CR.
MRD negativity was defined by the absence of tumor cells in bone marrow, using 4-color flow cytometry. MRD was assessed in participants with a confirmed CR. CR was achieved if all of the following criteria were met for ≥8 weeks: a)Absence of LD by PE and CT scan, b)No HM/SM by PE/CT scan, c)Absence of B symptoms, d)Normal CBC, and e)BM biopsy: normocellular for age, \<30% of the cells being Lym and LN absent.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=10 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Percentage of Participants Who Achieved Minimal Residual Disease (MRD) Negativity
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Day 1 of Cycles 5 and 11, end of follow-up (FU) (24 month [m] FU visit, up to approximately 3 years)Population: FAS. Number of participants analyzed = number of participants evaluable for this outcome and n=number of participants evaluable at the specified time point.
EORTC QLQ-C30: included global health status (GHS)/quality of life (QOL), functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Most questions used a 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used a 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; a higher score for Global Qol/functional scales=better level of QoL/functioning, or a higher score for symptom scale=greater degree of symptoms.
Outcome measures
| Measure |
Rituximab + Chlorambucil
n=91 Participants
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
Emotional functioning score-baseline (n=91)
|
82.5 units on scale
Standard Deviation 18.1
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in role functioning score-Cycle 5 (n=59)
|
0.0 units on scale
Standard Deviation 28.9
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in role functioning score-Cycle 11 (n=40)
|
3.8 units on scale
Standard Deviation 32.1
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in role functioning score-24m FU (n=17)
|
3.9 units on scale
Standard Deviation 20.0
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in physical functioning score-24m FU (n=17)
|
-2.0 units on scale
Standard Deviation 10.2
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
Role functioning score-baseline (n=91)
|
73.4 units on scale
Standard Deviation 31.6
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
GHS/QoL score-baseline (n=91)
|
65.7 units on scale
Standard Deviation 21.8
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in GHS/QoL Score-Cycle 5 (n=59)
|
6.4 units on scale
Standard Deviation 21.7
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in GHS/QoL Score-Cycle 11 (n=40)
|
6.2 units on scale
Standard Deviation 16.9
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in GHS/QoL Score-24m FU (n=17)
|
2.0 units on scale
Standard Deviation 15.2
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
Physical functioning score-baseline (n=91)
|
77.0 units on scale
Standard Deviation 22.3
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in physical functioning score-Cycle 5 (n=59)
|
1.0 units on scale
Standard Deviation 15.3
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in physical functioning score-Cycle 11 (n=40)
|
3.4 units on scale
Standard Deviation 22.0
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in emotional functioning score-Cycle 5 (n=59)
|
1.0 units on scale
Standard Deviation 16.5
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in emotional functioning score-Cycle 11 (n=40)
|
-0.1 units on scale
Standard Deviation 18.1
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in emotional functioning score-24m FU (n=17)
|
0.5 units on scale
Standard Deviation 17.3
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
Cognitive functioning score-baseline (n=91)
|
84.1 units on scale
Standard Deviation 19.1
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in cognitive functioning score-Cycle 5 (n=59)
|
-1.9 units on scale
Standard Deviation 15.4
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in cognitive functioning-Cycle 11 (n=40)
|
-0.4 units on scale
Standard Deviation 18.8
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in cognitive functioning-24m FU (n=17)
|
5.2 units on scale
Standard Deviation 18.0
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
Social functioning score-baseline (n=91)
|
82.2 units on scale
Standard Deviation 24.2
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in social functioning score-Cycle 5 (n=59)
|
2.5 units on scale
Standard Deviation 22.5
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in social functioning score-Cycle 11 (n=40)
|
0.0 units on scale
Standard Deviation 27.9
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in social functioning score-at 24m FU (n=17)
|
5.2 units on scale
Standard Deviation 19.9
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
Fatigue score-baseline (n=91)
|
33.4 units on scale
Standard Deviation 25.7
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in fatigue score-Cycle 5 (n=59)
|
-1.4 units on scale
Standard Deviation 24.9
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in fatigue score-Cycle 11 (n=40)
|
-6.1 units on scale
Standard Deviation 27.7
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in fatigue score-24m FU (n=17)
|
-5.6 units on scale
Standard Deviation 22.2
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
Nausea/vomiting score-baseline (n=91)
|
6.2 units on scale
Standard Deviation 16.2
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in nausea/vomiting score-Cycle 5 (n=59)
|
1.7 units on scale
Standard Deviation 20.9
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in nausea/vomiting score-Cycle 11 (n=40)
|
0.4 units on scale
Standard Deviation 20.8
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in nausea/vomiting score-24m FU (n=17)
|
-2.9 units on scale
Standard Deviation 8.8
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
Pain score-baseline (n=91)
|
17.8 units on scale
Standard Deviation 27.0
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in pain score-Cycle 5 (n=59)
|
-3.4 units on scale
Standard Deviation 28.8
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in pain score-Cycle 11 (n=40)
|
-1.3 units on scale
Standard Deviation 33.2
|
|
Mean Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scores
CFB in pain score-24m FU (n=17)
|
0.0 units on scale
Standard Deviation 31.2
|
Adverse Events
Rituximab + Chlorambucil
Serious adverse events
| Measure |
Rituximab + Chlorambucil
n=100 participants at risk
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Infections and infestations
Neutropenic sepsis
|
4.0%
4/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Pneumonia
|
2.0%
2/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Anal infection
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Bacterial sepsis
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Cellulitis
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Encephalitis viral
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Lower respiratory tract infection
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Lung infection
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Oral candidiasis
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Pseudomonal bacteraemia
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Staphylococcal skin infection
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Upper respiratory tract infection
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.0%
5/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Blood and lymphatic system disorders
Anaemia
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Blood and lymphatic system disorders
Haemolytic anaemia
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
General disorders
Infusion related reaction
|
3.0%
3/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
General disorders
Pyrexia
|
2.0%
2/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
General disorders
Oedema peripheral
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Gastrointestinal disorders
Vomiting
|
2.0%
2/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Gastrointestinal disorders
Diarrhoea
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Gastrointestinal disorders
Nausea
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Gastrointestinal disorders
Neutropenic colitis
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.0%
2/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
2.0%
2/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Nervous system disorders
Autonomic nervous system imbalance
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Nervous system disorders
Cerebral infarction
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Nervous system disorders
Dizziness
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Nervous system disorders
Loss of consciousness
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Nervous system disorders
Myoclonus
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Nervous system disorders
Syncope
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Immune system disorders
Cytokine release syndrome
|
2.0%
2/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Immune system disorders
Anaphylactic reaction
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Metabolism and nutrition disorders
Dehydration
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Metabolism and nutrition disorders
Malnutrition
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Hepatobiliary disorders
Cholecystitis acute
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Investigations
Staphylococcal indentification test positive
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Reproductive system and breast disorders
Scrotal oedema
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Vascular disorders
Ischaemia
|
1.0%
1/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
Other adverse events
| Measure |
Rituximab + Chlorambucil
n=100 participants at risk
Participants received combination therapy of rituximab plus chlorambucil for first 6 cycles. Participants who did not achieve CR after Cycle 6 then received chlorambucil alone from Cycle 7 onwards until either they achieved a CR or for a maximum of 6 additional cycles. Rituximab: 375 mg/m\^2 IV infusion on Day 1 of Cycle 1; 500 mg/m\^2 on Day 1 of Cycles 2-6. Chlorambucil: 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 1-6; 10 mg/m\^2/day PO on Days 1 to 7 of Cycles 7-12, if applicable.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
20.0%
20/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Blood and lymphatic system disorders
Leukopenia
|
23.0%
23/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Blood and lymphatic system disorders
Lymphopenia
|
41.0%
41/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Blood and lymphatic system disorders
Neutropenia
|
41.0%
41/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
19.0%
19/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Gastrointestinal disorders
Abdominal pain
|
7.0%
7/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Gastrointestinal disorders
Constipation
|
15.0%
15/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Gastrointestinal disorders
Diarrhoea
|
19.0%
19/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Gastrointestinal disorders
Dyspepsia
|
8.0%
8/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Gastrointestinal disorders
Mouth ulceration
|
5.0%
5/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Gastrointestinal disorders
Nausea
|
51.0%
51/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Gastrointestinal disorders
Vomiting
|
22.0%
22/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
General disorders
Chills
|
17.0%
17/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
General disorders
Fatigue
|
31.0%
31/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
General disorders
Infusion related reaction
|
5.0%
5/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
General disorders
Mucosal inflammation
|
6.0%
6/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
General disorders
Oedema peripheral
|
10.0%
10/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
General disorders
Pyrexia
|
27.0%
27/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Immune system disorders
Hypersensitivity
|
5.0%
5/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Cellulitis
|
5.0%
5/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Lower respiratory tract infection
|
11.0%
11/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Nasopharyngitis
|
9.0%
9/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Upper respiratory tract infection
|
16.0%
16/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Infections and infestations
Urinary tract infection
|
5.0%
5/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Metabolism and nutrition disorders
Anorexia
|
7.0%
7/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.0%
5/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
6.0%
6/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
5.0%
5/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.0%
9/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.0%
12/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.0%
6/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Nervous system disorders
Dizziness
|
15.0%
15/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Nervous system disorders
Headache
|
15.0%
15/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Nervous system disorders
Lethargy
|
7.0%
7/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Nervous system disorders
Paraesthesia
|
6.0%
6/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Nervous system disorders
Syncope
|
5.0%
5/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Psychiatric disorders
Insomnia
|
7.0%
7/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
20/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.0%
13/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
8.0%
8/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
6.0%
6/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.0%
13/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Vascular disorders
Flushing
|
8.0%
8/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Vascular disorders
Hypertension
|
6.0%
6/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
|
Vascular disorders
Hypotension
|
11.0%
11/100 • First administration of study treatment up to 56 days after the beginning of the last treatment cycle (up to 365 days)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER