Trial Outcomes & Findings for Rituximab and Alemtuzumab in Treating Older Patients With Progressive Chronic Lymphocytic Leukemia (NCT NCT01013961)
NCT ID: NCT01013961
Last Updated: 2023-06-28
Results Overview
Response was evaluated using NCI-WG96 criteria. A CR requires all of the following for \>= 2 months: * Absence of lymphadenopathy \> 1 cm in diameter by physical examination * No hepatomegaly or splenomegaly on physical exam * No constitutional symptoms * Normal complete blood count (CBC) * Patients achieving a clinical CR with negative CT scan after 2 cycles of therapy are re-evaluated using immunohistochemical examination of bone marrow biopsy for residual CLL cells. Patients with no evidence of residual disease and no radiological evidence of residual CLL on CT scan of chest-abdomen-pelvis and no clinical evidence of CLL on clinical evaluation after completion of 2 cycles of therapy will be considered to have a CR with no evidence of residual disease
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
31 participants
Primary outcome timeframe
Assessed after 2 cycles of treatment and 2 months after completion of therapy
Results posted on
2023-06-28
Participant Flow
This study was activated on October 8, 2010 and closed on October 31, 2013 with a total of 31 patients accrued. The first patient was accrued on April 27, 2011.
Peripheral blood (preferred) or bone marrow must be submitted at pre-registration for FISH risk analysis to determine stratification factor before randomization.
Participant milestones
| Measure |
Arm A (Standard Dose)
Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab 375 mg/m\^2/week intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
Arm B (Low Dose)
Patients receive alemtuzumab SC on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and low-dose rituximab at 20 mg/m\^2 IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC and low-dose rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
15
|
|
Overall Study
COMPLETED
|
13
|
12
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
| Measure |
Arm A (Standard Dose)
Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab 375 mg/m\^2/week intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
Arm B (Low Dose)
Patients receive alemtuzumab SC on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and low-dose rituximab at 20 mg/m\^2 IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC and low-dose rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
Rituximab and Alemtuzumab in Treating Older Patients With Progressive Chronic Lymphocytic Leukemia
Baseline characteristics by cohort
| Measure |
Arm A (Standard Dose)
n=16 Participants
Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab 375 mg/m\^2/week intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
Arm B (Low Dose)
n=15 Participants
Patients receive alemtuzumab SC on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and low-dose rituximab at 20 mg/m\^2 IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC and low-dose rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
Total
n=31 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
77 years
n=5 Participants
|
76 years
n=7 Participants
|
76 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Assessed after 2 cycles of treatment and 2 months after completion of therapyPopulation: All randomized patients
Response was evaluated using NCI-WG96 criteria. A CR requires all of the following for \>= 2 months: * Absence of lymphadenopathy \> 1 cm in diameter by physical examination * No hepatomegaly or splenomegaly on physical exam * No constitutional symptoms * Normal complete blood count (CBC) * Patients achieving a clinical CR with negative CT scan after 2 cycles of therapy are re-evaluated using immunohistochemical examination of bone marrow biopsy for residual CLL cells. Patients with no evidence of residual disease and no radiological evidence of residual CLL on CT scan of chest-abdomen-pelvis and no clinical evidence of CLL on clinical evaluation after completion of 2 cycles of therapy will be considered to have a CR with no evidence of residual disease
Outcome measures
| Measure |
Arm A (Standard Dose)
n=16 Participants
Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab 375 mg/m\^2/week intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
Arm B (Low Dose)
n=15 Participants
Patients receive alemtuzumab SC on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and low-dose rituximab at 20 mg/m\^2 IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC and low-dose rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
|---|---|---|
|
Proportion of Patients With Complete Response (CR)
|
0.5 proportion of participants
Interval 0.247 to 0.753
|
0.4 proportion of participants
Interval 0.163 to 0.677
|
PRIMARY outcome
Timeframe: Assessed after 2 cycles of treatment and 2 months after completion of therapyPopulation: All randomized patients
OR is defined as either CR, clinical CR, or partial response (PR) evaluated by NCI-WG96 criteria. CR has been defined in the other primary endpoint. A clinical CR requires all of the following: * Absence of lymphadenopathy by physical examination * No hepatomegaly or splenomegaly. Spleen and/or liver, if considered enlarged at baseline, should not be palpable, due to disease, on physical exam * Absence of constitutional symptoms * Normal CBC as exhibited by: A PR requires all the following for ≥2 months: * ≥50% decrease in peripheral blood lymphocyte count from baseline * ≥50% reduction in lymphadenopathy * ≥50% reduction in size of liver and/or spleen * Polymorphonuclear leukocytes ≥1.5x10\^9/L or 50% improvement over baseline * Platelets \>100x10\^9/L or 50% improvement over baseline * Hemoglobin \>11.0 gm/dl or 50% improvement over baseline without transfusions * Any constitutional symptoms
Outcome measures
| Measure |
Arm A (Standard Dose)
n=16 Participants
Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab 375 mg/m\^2/week intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
Arm B (Low Dose)
n=15 Participants
Patients receive alemtuzumab SC on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and low-dose rituximab at 20 mg/m\^2 IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC and low-dose rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
|---|---|---|
|
Proportion of Patients With Overall Response (OR)
|
0.875 proportion of participants
Interval 0.617 to 0.985
|
0.933 proportion of participants
Interval 0.681 to 0.998
|
SECONDARY outcome
Timeframe: Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 yearsPopulation: All randomized patients
OS is defined to be time from randomization to death from any cause. Those still alive are censored at the date of last contact.
Outcome measures
| Measure |
Arm A (Standard Dose)
n=16 Participants
Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab 375 mg/m\^2/week intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
Arm B (Low Dose)
n=15 Participants
Patients receive alemtuzumab SC on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and low-dose rituximab at 20 mg/m\^2 IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC and low-dose rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
|---|---|---|
|
Overall Survival (OS)
|
NA months
Interval 22.3 to
Median OS was not reached. The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
NA months
Interval 32.8 to
Median OS was not reached. The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
SECONDARY outcome
Timeframe: Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 yearsPopulation: All randomized patients
PFS is defined to be time from randomization to progression (PD) or to death without documentation of progression. For patients without PD, follow-up is censored at the date of last disease assessment without PD, unless death occurs within three months following the date last known progression free. PD is characterized by at least one of the following: * ≥50% increase in the sum of the products of at least 2 lymph nodes on 2 consecutive examinations 2 weeks apart (at least 1 node must be \>2 cm). Appearance of new palpable lymph nodes (\>1 cm in diameter). * ≥50% increase in the size of liver and/or spleen as determined by measurement below the respective costal margin; appearance of palpable hepatomegaly or splenomegaly which was not previously present. * Absolute number of circulating lymphocytes with a count of \>5x10\^9/L * Transformation to a more aggressive histology
Outcome measures
| Measure |
Arm A (Standard Dose)
n=16 Participants
Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab 375 mg/m\^2/week intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
Arm B (Low Dose)
n=15 Participants
Patients receive alemtuzumab SC on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and low-dose rituximab at 20 mg/m\^2 IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC and low-dose rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
|---|---|---|
|
Progression-free Survival (PFS)
|
12.8 months
Interval 11.7 to
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
23.3 months
Interval 14.8 to
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
SECONDARY outcome
Timeframe: Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 yearsPopulation: All randomized patients
Time to response is defined to be time from randomization to first confirmed CR, PR or clinical CR. Those without confirmed CR, PR or clinical CR are censored at the date of last disease assessment.
Outcome measures
| Measure |
Arm A (Standard Dose)
n=16 Participants
Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab 375 mg/m\^2/week intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
Arm B (Low Dose)
n=15 Participants
Patients receive alemtuzumab SC on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and low-dose rituximab at 20 mg/m\^2 IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC and low-dose rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
|---|---|---|
|
Time to Response
|
4.8 months
Interval 4.6 to 5.7
|
4.7 months
Interval 2.7 to 6.5
|
SECONDARY outcome
Timeframe: Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 yearsPopulation: All randomized patients
Duration of response is defined to be time from first confirmed CR, PR or clinical CR to progression or to death without documentation of progression. Patients without confirmed CR, PR or clinical CR are censored at time 0. Those without documentation of progression are censored at the date of last disease assessment without progression, unless death occurs within three months following the date last known progression free.
Outcome measures
| Measure |
Arm A (Standard Dose)
n=16 Participants
Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab 375 mg/m\^2/week intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
Arm B (Low Dose)
n=15 Participants
Patients receive alemtuzumab SC on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and low-dose rituximab at 20 mg/m\^2 IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC and low-dose rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
|---|---|---|
|
Duration of Response
|
9.8 months
Interval 7.7 to
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
16.8 months
Interval 10.1 to
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
Adverse Events
Arm A (Standard Dose)
Serious events: 16 serious events
Other events: 16 other events
Deaths: 0 deaths
Arm B (Low Dose)
Serious events: 15 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm A (Standard Dose)
n=16 participants at risk
Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab 375 mg/m\^2/week intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
Arm B (Low Dose)
n=15 participants at risk
Patients receive alemtuzumab SC on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and low-dose rituximab at 20 mg/m\^2 IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC and low-dose rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
12.5%
2/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
General disorders
Fatigue
|
12.5%
2/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
13.3%
2/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Mucositis oral
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Immune system disorders
Serum sickness
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Lung infection
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Tooth infection
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Lipase increased
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Lymphocyte count decreased
|
100.0%
16/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
100.0%
15/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Lymphocyte count increased
|
18.8%
3/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
40.0%
6/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Neutrophil count decreased
|
75.0%
12/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
46.7%
7/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Platelet count decreased
|
18.8%
3/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Weight loss
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
White blood cell decreased
|
68.8%
11/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
60.0%
9/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Investigations - Other, specify
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hyponatremia
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Nervous system disorders - Other
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
Other adverse events
| Measure |
Arm A (Standard Dose)
n=16 participants at risk
Patients receive alemtuzumab subcutaneously (SC) on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and standard-dose rituximab 375 mg/m\^2/week intravenously (IV) on days 8, 15, 22, and 29 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and standard-dose rituximab IV on days 3, 10, 17, and 24. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
Arm B (Low Dose)
n=15 participants at risk
Patients receive alemtuzumab SC on days 1-3, 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 and low-dose rituximab at 20 mg/m\^2 IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 (33-day cycle). In cycle 2 and subsequent cycles (28-day cycle), patients receive alemtuzumab SC and low-dose rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 3 cycles.
Alemtuzumab dose for cycle 1 week 1 requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1) and then is 30 mg 3 times a week.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
13.3%
2/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Dizziness
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Dysgeusia
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Headache
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Presyncope
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Tremor
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Psychiatric disorders
Confusion
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Blood and lymphatic system disorders
Anemia
|
100.0%
16/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
93.3%
14/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
General disorders
Chills
|
18.8%
3/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
General disorders
Fatigue
|
50.0%
8/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
46.7%
7/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
General disorders
Fever
|
18.8%
3/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
13.3%
2/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
General disorders
Injection site reaction
|
12.5%
2/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
General disorders
Malaise
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
18.8%
3/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Mucositis oral
|
12.5%
2/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Nausea
|
18.8%
3/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
2/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Immune system disorders
Allergic reaction
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Bladder infection
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Mucosal infection
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Sinusitis
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Urinary tract infection
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Infections and infestations - Other
|
12.5%
2/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
26.7%
4/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Aspartate aminotransferase increased
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
CD4 lymphocytes decreased
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Creatinine increased
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Lymphocyte count decreased
|
37.5%
6/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
73.3%
11/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Lymphocyte count increased
|
43.8%
7/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
46.7%
7/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Neutrophil count decreased
|
56.2%
9/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
53.3%
8/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Platelet count decreased
|
68.8%
11/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
66.7%
10/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Weight loss
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
White blood cell decreased
|
81.2%
13/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
100.0%
15/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Anorexia
|
12.5%
2/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
20.0%
3/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
6.7%
1/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Renal and urinary disorders
Chronic kidney disease
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
|
Vascular disorders
Hypotension
|
6.2%
1/16 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
0.00%
0/15 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
|
Additional Information
Study Statistician
ECOG-ACRIN Statistical Office
Phone: 617-632-3012
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60