Rituximab and Alemtuzumab in Treating Older Patients With... | NCT01013961

ID	Type	Description	Link
E1908	Other Identifier	ECOG-ACRIN Cancer Research Group
U10CA180794	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

OBJECTIVES:

Primary

To compare the rate of complete and overall response in elderly patients with progressive chronic lymphocytic leukemia (CLL) treated with one of two doses of rituximab combined with alemtuzumab to determine if the use of modified-dose rituximab significantly affects outcome.

Secondary

To monitor and assess toxicity of these regimens.
To determine the overall and progression-free survival, time to clinical response, time to next treatment, and duration of response in patients treated with these regimens
To assess the correlation between risk stratification prognostic markers (i.e., CD38, ZAP-70, fluorescent in situ hybridization (FISH), and IgVH mutation) and clinical outcome.
To assess response to these regimens using both the 1996 National Cancer Institute Working Group (NCI-WG 96) criteria and an expanded definition of response for patients in complete remission, including immunohistochemical examination of the bone marrow and sensitive flow cytometry (4-6 color) of blood for minimal residual disease and computed tomography (CT) scans for residual adenopathy.
To determine the mechanism of action of rituximab and alemtuzumab and to determine mechanisms of resistance of a subpopulation of CLL cells to these drugs.

OUTLINE: This is a multicenter study. Patients are stratified according to FISH risk (low [13q14-] vs intermediate [12+, no abnormality, all other abnormalities] vs high [17p13-,11q22-]). Patients are randomized to 1 of 2 treatment arms.

Arm A: 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 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.
Arm B: Patients receive alemtuzumab as in arm A. Patients also receive low-dose rituximab IV on days 6, 8, 10, 13, 15, 17, 20, 22, 24, 27, 29, and 31 in cycle 1 and on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 in cycless 2 and 3. Treatment repeats every 28 days for up to 3 cycles.

Blood and bone marrow samples are collected periodically for cytogenetic and biomarker analysis.

Alemtuzumab dose for Cycle 1 Week 1 of both Arms A and B requires a 'dose ramp' (3 mg day 1, 10 mg day2, and 30 mg day 3 of cycle 1).

After completion of study therapy, patients are followed up periodically for 5 years.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A (standard dose)	Active Comparator	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.	Biological: alemtuzumab Biological: rituximab
Arm B (low dose)	Experimental	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.	Biological: alemtuzumab Biological: rituximab

Name	Type	Description	Arm Group Labels	Other Names
alemtuzumab	Biological	Given IV	Arm A (standard dose) Arm B (low dose)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Proportion of Patients With Complete Response (CR)	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	Assessed after 2 cycles of treatment and 2 months after completion of therapy
Proportion of Patients With Overall Response (OR)	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	Assessed after 2 cycles of treatment and 2 months after completion of therapy

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	OS is defined to be time from randomization to death from any cause. Those still alive are censored at the date of last contact.	Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years
Progression-free Survival (PFS)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis of chronic lymphocytic leukemia (CLL) meeting the following criteria:
- Minimum threshold peripheral lymphocyte count of 5 x 10^9/L (CLL variant) OR palpable adenopathy > 1 cm or palpable splenomegaly 9small lymphocytic lymphoma [SLL] variant)
- Immunophenotypic demonstrations of a population of B-lymphocytes (as defined by CD19+) that are monoclonal (by light-chain exclusion) AND have ≥ 3 of the following characteristics:
  - CD5+
  - CD23+
  - Dim surface light chain expression
  - Dim surface CD20 expression
- FISH analysis is negative for immunoglobulin heavy chain/cyclin D1 gene (IGH/CCND1) and/or immunostaining is negative for cyclin D1 expression (to exclude mantle cell lymphoma)
Progressive, symptomatic CLL, defined by at least one of the following:
- Weight loss > 10% within the past 6 months attributable to progressive CLL (grade 2 or higher)
- Extreme fatigue attributable to progressive CLL (grade 3 or higher)
- Fevers > 100.5° F for 2 weeks without evidence of infection (grade 1 or higher)
- Night sweats without evidence of infection (drenching)
- Evidence of progressive bone marrow failure with hemoglobin < 11 g/dL or platelet count < 100 x 10^9/L
- Rapidly progressive lymphadenopathy for which the largest node is ≤ 5 cm in any dimension
  - Largest lymph nodes involved in the neck, axilla, and groin need to be measured and followed for response

Exclusion Criteria:

Prior treatment for CLL
Massive splenomegaly > 6 cm below left costal margin, at rest, on clinical examination
Lymphadenopathy > 5 cm in any diameter
New York Heart Association class III or IV heart disease
Recent myocardial infarction (within the past month)
Uncontrolled infection
Infection with the human immunodeficiency virus (HIV/AIDS)
Serological evidence of active hepatitis B infection (HBsAg or HBeAg positive)
Positive hepatitis C serology
Evidence of active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
Other active primary malignancy requiring treatment or that limits survival to ≤ 2 years, except for in situ carcinoma of the cervix or breast or non-metastatic basal cell or squamous cell carcinoma of the skin
Major surgery within 4 weeks prior to pre-registration
Concomitant use of continuous systemic corticosteroids
- Prior corticosteroids are allowed but not at time of pre-registration to the study

Name	Affiliation	Role
Clive S. Zent, MD	University of Rochester	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic Scottsdale		Scottsdale	Arizona	85259-5499	United States
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Proportion of Patients With Complete Response (CR)

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

All randomized patients

Posted

Number

95% Confidence Interval

proportion of participants

Assessed after 2 cycles of treatment and 2 months after completion of therapy

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00016 OG00115

Title

Denominators

Categories

Title	Measurements
	OG0000.5(0.247 to 0.753) OG0010.4(0.163 to 0.677)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Fisher Exact		0.722						2-Sided								Superiority or Other (legacy)

Primary

Proportion of Patients With Overall Response (OR)

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

All randomized patients

Posted

Number

95% Confidence Interval

proportion of participants

Assessed after 2 cycles of treatment and 2 months after completion of therapy

ID	Title	Description
OG000	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.

Secondary

Overall Survival (OS)

OS is defined to be time from randomization to death from any cause. Those still alive are censored at the date of last contact.

All randomized patients

Posted

Median

95% Confidence Interval

months

Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Progression-free Survival (PFS)

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

All randomized patients

Posted

Median

95% Confidence Interval

months

Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years

ID	Title	Description
OG000	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.

Secondary

Time to Response

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.

All randomized patients

Posted

Median

95% Confidence Interval

months

Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Duration of Response

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.

All randomized patients

Posted

Median

95% Confidence Interval

months

Assessed after 2 cycles of treatment, 2 months after completion of therapy and then yearly up to 5 years

ID	Title	Description
OG000	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.
OG001	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.			16	16	16	16
EG001	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.			15	15	15	15

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0011 affected15 at risk
Febrile neutropenia	Blood and lymphatic system disorders	CTCAE 4.0	Systematic Assessment	EG0002 affected16 at risk EG0011 affected15 at risk
Fatigue	General disorders	CTCAE 4.0	Systematic Assessment	EG0002 affected16 at risk EG0011 affected15 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0012 affected15 at risk
Mucositis oral	Gastrointestinal disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Serum sickness	Immune system disorders	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
Lung infection	Infections and infestations	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
Tooth infection	Infections and infestations	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Lipase increased	Investigations	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Lymphocyte count decreased	Investigations	CTCAE 4.0	Systematic Assessment	EG00016 affected16 at risk EG00115 affected15 at risk
Lymphocyte count increased	Investigations	CTCAE 4.0	Systematic Assessment	EG0003 affected16 at risk EG0016 affected15 at risk
Neutrophil count decreased	Investigations	CTCAE 4.0	Systematic Assessment	EG00012 affected16 at risk EG0017 affected15 at risk
Platelet count decreased	Investigations	CTCAE 4.0	Systematic Assessment	EG0003 affected16 at risk EG0011 affected15 at risk
Weight loss	Investigations	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
White blood cell decreased	Investigations	CTCAE 4.0	Systematic Assessment	EG00011 affected16 at risk EG0019 affected15 at risk
Investigations - Other, specify	Investigations	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
Hyponatremia	Metabolism and nutrition disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0011 affected15 at risk
Nervous system disorders - Other	Nervous system disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE 4.0	Systematic Assessment	EG00016 affected16 at risk EG00114 affected15 at risk
Atrial fibrillation	Cardiac disorders	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
Chills	General disorders	CTCAE 4.0	Systematic Assessment	EG0003 affected16 at risk EG0011 affected15 at risk
Fatigue	General disorders	CTCAE 4.0	Systematic Assessment	EG0008 affected16 at risk EG0017 affected15 at risk
Fever	General disorders	CTCAE 4.0	Systematic Assessment	EG0003 affected16 at risk EG0012 affected15 at risk
Injection site reaction	General disorders	CTCAE 4.0	Systematic Assessment	EG0002 affected16 at risk EG0011 affected15 at risk
Malaise	General disorders	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	CTCAE 4.0	Systematic Assessment	EG0003 affected16 at risk EG0011 affected15 at risk
Mucositis oral	Gastrointestinal disorders	CTCAE 4.0	Systematic Assessment	EG0002 affected16 at risk EG0010 affected15 at risk
Nausea	Gastrointestinal disorders	CTCAE 4.0	Systematic Assessment	EG0003 affected16 at risk EG0010 affected15 at risk
Vomiting	Gastrointestinal disorders	CTCAE 4.0	Systematic Assessment	EG0002 affected16 at risk EG0010 affected15 at risk
Allergic reaction	Immune system disorders	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
Bladder infection	Infections and infestations	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
Mucosal infection	Infections and infestations	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Sinusitis	Infections and infestations	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Urinary tract infection	Infections and infestations	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Infections and infestations - Other	Infections and infestations	CTCAE 4.0	Systematic Assessment	EG0002 affected16 at risk EG0014 affected15 at risk
Alanine aminotransferase increased	Investigations	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
Aspartate aminotransferase increased	Investigations	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0011 affected15 at risk
Blood bilirubin increased	Investigations	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
CD4 lymphocytes decreased	Investigations	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
Creatinine increased	Investigations	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0011 affected15 at risk
Lymphocyte count decreased	Investigations	CTCAE 4.0	Systematic Assessment	EG0006 affected16 at risk EG00111 affected15 at risk
Lymphocyte count increased	Investigations	CTCAE 4.0	Systematic Assessment	EG0007 affected16 at risk EG0017 affected15 at risk
Neutrophil count decreased	Investigations	CTCAE 4.0	Systematic Assessment	EG0009 affected16 at risk EG0018 affected15 at risk
Platelet count decreased	Investigations	CTCAE 4.0	Systematic Assessment	EG00011 affected16 at risk EG00110 affected15 at risk
Weight loss	Investigations	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
White blood cell decreased	Investigations	CTCAE 4.0	Systematic Assessment	EG00013 affected16 at risk EG00115 affected15 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE 4.0	Systematic Assessment	EG0002 affected16 at risk EG0013 affected15 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0011 affected15 at risk
Myalgia	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0012 affected15 at risk
Dizziness	Nervous system disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0011 affected15 at risk
Dysgeusia	Nervous system disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Headache	Nervous system disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Presyncope	Nervous system disorders	CTCAE 4.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected15 at risk
Tremor	Nervous system disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Confusion	Psychiatric disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0011 affected15 at risk
Chronic kidney disease	Renal and urinary disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk
Hypotension	Vascular disorders	CTCAE 4.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected15 at risk

ID	Term
D015448	Leukemia, B-Cell
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D058846	Antibodies, Monoclonal, Murine-Derived