Pentostatin, Alemtuzumab, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00669318
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 41
• Locations: 3
• Arm: 1
• Duration (Months): 70
• Patients Per Site: 13.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as pentostatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as alemtuzumab and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving pentostatin together with alemtuzumab and rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving pentostatin together with alemtuzumab and rituximab works in treating patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Lymphoma	Biological: alemtuzumab; Biological: rituximab; Drug: pentostatin; Drug: sargramostim	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To assess the rate of complete and overall response in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma treated with pentostatin, alemtuzumab, and low-dose rituximab.

• To monitor and assess toxicity of this treatment regimen.

Secondary

• To determine the overall and progression-free survival, duration of response, and time to next treatment.

• To assess the correlation between individual prognostic markers (17p-, 11q-, unmutated VH gene, VH3-21, ZAP-70+, CD38+, CD49d, and β2 microglobulin, miRNA profiles, angiogenesis status, and karyotypes of CpG stimulated cells) and clinical outcome.

OUTLINE: This is a multicenter study.

• Course 1: Patients receive pentostatin IV on days 8 and 22; alemtuzumab subcutaneously (SC) on days 3-5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; and sargramostim (GM-CSF) SC on days 10-14 and 24-28. Patients then proceed to course 2.

• Courses 2 and 3: Patients receive pentostatin IV on days 1 and 15; alemtuzumab SC and rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; and GM-CSF SC on days 3-7 and 17-21. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).

Treatment continues in the absence of disease progression or unacceptable toxicity.

Blood is collected on days 1, 3, 8, and 10 of course 1 for monoclonal antibody studies. Samples are analyzed for serum concentration of alemtuzumab and rituximab by ELISA and PCR; CH50 assay; complement activation and cytokine levels by ELISA; NK cell activation; and NK cell phenotype by immunofluorescent staining and flow cytometry.

After completion of study treatment, patients are followed up monthly for 6 months, every 3 months for 6 months, and then every 6-12 months for up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) With Pentostatin, Alemtuzumab, and Low Dose Rituximab: A Phase II Clinical Trial
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (Pentostatin, Alemtuzumab, Rituximab) Course 1: Patients receive: 2 mg/m^2 pentostatin IV on days 8 and 22; 3 mg alemtuzumab subcutaneously (SC) on day 3; 10 mg alemtuzumab SC on day 4; 30 mg alemtuzumab SC on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 6 mg Sargramostim (GM-CSF) SC on days 10-14. Patients then proceed to course 2. Courses 2 and 3: Patients receive: 2 mg/m^2 pentostatin IV on days 1 and 15; 30 mg alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 6 mg GM-CSF SC on days 3-7. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).

Biological: alemtuzumab; Biological: rituximab; Drug: pentostatin; Drug: sargramostim; Other Names: GM-CSF

Outcome Measures

Primary Outcome Measures

1. Complete Response Rate [Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total)]

   A Complete Response (CR) requires the disappearance of all nodes, a non-palpable liver and spleen, no constitutional symptoms, absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, and lymphocytes <4000/uL. In addition, a bone marrow biopsy with evidence of <30% lymphocytes and no nodules. Here we report the rate of complete response as the number of patients attaining a CR status divided by the total number of evaluable patients. The 95% CI is estimated using the binomial distribution.

Secondary Outcome Measures

1. Overall Response Rate (Complete and Partial Response) [Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total)]

   A Complete Response (CR) requires the disappearance of all nodes, a non-palpable liver and spleen, no constitutional symptoms, absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, and lymphocytes <4000/uL. A bone marrow biopsy with evidence of <30% lymphocytes and no nodules. Patients who fulfill all criteria for a CR but have a persistent anemia, thrombocytopenia, or neutropenia related to drug toxicity will be classified as CR with incomplete marrow recovery (CRi). A Partial Response (PR) requires a 50% reduction in nodes and liver/spleen measurements and at least two of the following: absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, or a >50% reduction in lymphocytes. Here we report the rate of overall response as the number of patients attaining a CR, PR, or CRi status divided by the total number of evaluable patients. The 95% CI is estimated using the binomial distribution.

2. Overall Survival [Follow-up status and retreatment information will be collected up to 5 years from registration]

   Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

3. Progression-free Survival [Follow-up status and retreatment information will be collected up to 5 years from registration]

   The progression-free survival (PFS) time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

4. Time to Retreatment [Follow-up status and retreatment information will be collected up to 5 years from registration]

   Time to subsequent therapy is defined to be the time from the registration to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) meeting the following criteria:

• Minimum threshold peripheral blood lymphocyte count of 5 x 10^9/L (CLL variant) OR adenopathy > 1 cm or palpable splenomegaly (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 IGH/CCND1 and/or immunostaining is negative for cyclin D1 expression

• Must have progressive disease as indicated by any of the following characteristics (based on standard criteria for treatment):

• Symptomatic CLL characterized by any of the following:

• Weight loss > 10% within the past 6 months

• Extreme fatigue

• Fevers > 38.5° C (not due to infection)

• Drenching night sweats without evidence of infection

• Evidence of progressive bone marrow failure with hemoglobin < 11 g/dL or platelet count < 100 x 10^9/L

• Massive and progressive splenomegaly (> 6 cm below left costal margin)

• Massive (> 10 cm) or rapidly progressive lymphadenopathy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3

• Creatinine ≤ 2 times upper limit of normal (ULN)

• Total bilirubin ≤ 3.0 times ULN OR direct bilirubin ≤ 1.5 times ULN

• AST ≤ 3.0 times ULN (unless due to hemolysis or CLL)

• Willing to provide mandatory blood samples for research studies

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for up to 12 months after completion of study treatment

• No other active primary malignancy that requires treatment or limits survival to ≤ 2 years

• No active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia

• No New York Heart Association class III or IV heart disease

• No myocardial infarction within the past month

• No uncontrolled infection

• No HIV infection or AIDS

• No active hepatitis B infection (i.e., HBsAg or HBeAg positivity) or hepatitis C infection by serology

• No other comorbid condition

PRIOR CONCURRENT THERAPY:

• No more than 3 prior treatment regimens for CLL that included purine analogue drugs (e.g., fludarabine, pentostatin, or cladribine) OR previously untreated CLL in patients with high-risk disease due to 17p13 deletion on FISH analysis

• More than 4 weeks since prior major surgery

• More than 2 months since prior alemtuzumab

• Prior corticosteroids allowed

• No concurrent continuous systemic corticosteroids

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1002
2	Mayo Clinic	Rochester	Minnesota	United States	55905
3	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

• Mayo Clinic
• National Cancer Institute (NCI)

Investigators

• Study Chair: Clive S. Zent, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00669318
• Other Study ID Numbers: LS0881; LS0881; 08-000673
• First Posted: Apr 30, 2008
• Last Update Posted: Jul 1, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by Mayo Clinic: refractory chronic lymphocytic leukemia; recurrent small lymphocytic lymphoma; B-cell chronic lymphocytic leukemia
• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Rituximab; Alemtuzumab; Pentostatin; Sargramostim

Study Results

Participant Flow

Recruitment Details	Forty-one patients were enrolled from July 2008 to February 2013 and 39 were evaluable. Two patients did not start treatment. One patient was found to have concomitant Hodgkin lymphoma and the other a serious systemic infection during pre-treatment evaluation. The characteristics of the 39 evaluable patients are summarized

Arm/Group Title	Treatment (Pentostatin, Alemtuzumab, Rituximab)
Arm/Group Description	Course 1: Patients receive: 2 mg/m^2 pentostatin IV on days 8 and 22; 3 mg alemtuzumab subcutaneously (SC) on day 3; 10 mg alemtuzumab SC on day 4; 30 mg alemtuzumab SC on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 6 mg Sargramostim (GM-CSF) SC on days 10-14. Patients then proceed to course 2. Courses 2 and 3: Patients receive: 2 mg/m^2 pentostatin IV on days 1 and 15; 30 mg alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 6 mg GM-CSF SC on days 3-7. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).
Period Title: Overall Study
STARTED	41
COMPLETED	39
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment (Pentostatin, Alemtuzumab, Rituximab)
Arm/Group Description	Course 1: Patients receive: 2 mg/m^2 pentostatin IV on days 8 and 22; 3 mg alemtuzumab subcutaneously (SC) on day 3; 10 mg alemtuzumab SC on day 4; 30 mg alemtuzumab SC on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 6 mg Sargramostim (GM-CSF) SC on days 10-14. Patients then proceed to course 2. Courses 2 and 3: Patients receive: 2 mg/m^2 pentostatin IV on days 1 and 15; 30 mg alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 6 mg GM-CSF SC on days 3-7. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).
Overall Participants	39
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	9 23.1%
Male	30 76.9%
Region of Enrollment (participants) [Number]
United States	39 100%

Outcome Measures

1. Primary Outcome

Title	Complete Response Rate
Description	A Complete Response (CR) requires the disappearance of all nodes, a non-palpable liver and spleen, no constitutional symptoms, absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, and lymphocytes <4000/uL. In addition, a bone marrow biopsy with evidence of <30% lymphocytes and no nodules. Here we report the rate of complete response as the number of patients attaining a CR status divided by the total number of evaluable patients. The 95% CI is estimated using the binomial distribution.
Time Frame	Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Pentostatin, Alemtuzumab, Rituximab)
Arm/Group Description	Course 1: Patients receive: 2 mg/m^2 pentostatin IV on days 8 and 22; 3 mg alemtuzumab subcutaneously (SC) on day 3; 10 mg alemtuzumab SC on day 4; 30 mg alemtuzumab SC on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 6 mg Sargramostim (GM-CSF) SC on days 10-14. Patients then proceed to course 2. Courses 2 and 3: Patients receive: 2 mg/m^2 pentostatin IV on days 1 and 15; 30 mg alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 6 mg GM-CSF SC on days 3-7. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).
Measure Participants	39
Number (95% Confidence Interval) [percentage of participants]	10 25.6%

2. Secondary Outcome

Title	Overall Response Rate (Complete and Partial Response)
Description	A Complete Response (CR) requires the disappearance of all nodes, a non-palpable liver and spleen, no constitutional symptoms, absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, and lymphocytes <4000/uL. A bone marrow biopsy with evidence of <30% lymphocytes and no nodules. Patients who fulfill all criteria for a CR but have a persistent anemia, thrombocytopenia, or neutropenia related to drug toxicity will be classified as CR with incomplete marrow recovery (CRi). A Partial Response (PR) requires a 50% reduction in nodes and liver/spleen measurements and at least two of the following: absolute neutrophil counts >1500/uL, platelets >100000/uL, Hemoglobin >11.0 g/dL, or a >50% reduction in lymphocytes. Here we report the rate of overall response as the number of patients attaining a CR, PR, or CRi status divided by the total number of evaluable patients. The 95% CI is estimated using the binomial distribution.
Time Frame	Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Pentostatin, Alemtuzumab, Rituximab)
Arm/Group Description	Course 1: Patients receive: 2 mg/m^2 pentostatin IV on days 8 and 22; 3 mg alemtuzumab subcutaneously (SC) on day 3; 10 mg alemtuzumab SC on day 4; 30 mg alemtuzumab SC on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 6 mg Sargramostim (GM-CSF) SC on days 10-14. Patients then proceed to course 2. Courses 2 and 3: Patients receive: 2 mg/m^2 pentostatin IV on days 1 and 15; 30 mg alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 6 mg GM-CSF SC on days 3-7. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).
Measure Participants	39
Number (95% Confidence Interval) [percentage of patients]	56

3. Secondary Outcome

Title	Overall Survival
Description	Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time Frame	Follow-up status and retreatment information will be collected up to 5 years from registration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Pentostatin, Alemtuzumab, Rituximab)
Arm/Group Description	Course 1: Patients receive: 2 mg/m^2 pentostatin IV on days 8 and 22; 3 mg alemtuzumab subcutaneously (SC) on day 3; 10 mg alemtuzumab SC on day 4; 30 mg alemtuzumab SC on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 6 mg Sargramostim (GM-CSF) SC on days 10-14. Patients then proceed to course 2. Courses 2 and 3: Patients receive: 2 mg/m^2 pentostatin IV on days 1 and 15; 30 mg alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 6 mg GM-CSF SC on days 3-7. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).
Measure Participants	39
Median (95% Confidence Interval) [months]	34.1

4. Secondary Outcome

Title	Progression-free Survival
Description	The progression-free survival (PFS) time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
Time Frame	Follow-up status and retreatment information will be collected up to 5 years from registration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Pentostatin, Alemtuzumab, Rituximab)
Arm/Group Description	Course 1: Patients receive: 2 mg/m^2 pentostatin IV on days 8 and 22; 3 mg alemtuzumab subcutaneously (SC) on day 3; 10 mg alemtuzumab SC on day 4; 30 mg alemtuzumab SC on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 6 mg Sargramostim (GM-CSF) SC on days 10-14. Patients then proceed to course 2. Courses 2 and 3: Patients receive: 2 mg/m^2 pentostatin IV on days 1 and 15; 30 mg alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 6 mg GM-CSF SC on days 3-7. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).
Measure Participants	39
Median (95% Confidence Interval) [months]	7.2

5. Secondary Outcome

Title	Time to Retreatment
Description	Time to subsequent therapy is defined to be the time from the registration to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier
Time Frame	Follow-up status and retreatment information will be collected up to 5 years from registration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Pentostatin, Alemtuzumab, Rituximab)
Arm/Group Description	Course 1: Patients receive: 2 mg/m^2 pentostatin IV on days 8 and 22; 3 mg alemtuzumab subcutaneously (SC) on day 3; 10 mg alemtuzumab SC on day 4; 30 mg alemtuzumab SC on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; 6 mg Sargramostim (GM-CSF) SC on days 10-14. Patients then proceed to course 2. Courses 2 and 3: Patients receive: 2 mg/m^2 pentostatin IV on days 1 and 15; 30 mg alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 20 mg/m^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; 6 mg GM-CSF SC on days 3-7. After completion of course 2, patients with a complete response proceed to observation. Patients with a partial response or stable disease receive another course of therapy (course 3).
Measure Participants	39
Median (95% Confidence Interval) [months]	9.1

Adverse Events

Arm/Group Title	Treatment (Pentostatin, Alemtuzumab, Rituximab)
Arm/Group Description	sargramostim
All Cause Mortality
	Treatment (Pentostatin, Alemtuzumab, Rituximab)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Pentostatin, Alemtuzumab, Rituximab)
	Affected / at Risk (%)	# Events
Total	4/39 (10.3%)
Infections and infestations
Pneumonia	1/39 (2.6%)	1
Skin infection	1/39 (2.6%)	1
Investigations
Neutrophil count decreased	2/39 (5.1%)	2
Other (Not Including Serious) Adverse Events
	Treatment (Pentostatin, Alemtuzumab, Rituximab)
	Affected / at Risk (%)	# Events
Total	38/39 (97.4%)
Blood and lymphatic system disorders
Blood disorder	1/39 (2.6%)	1
Febrile neutropenia	3/39 (7.7%)	3
Hemoglobin decreased	22/39 (56.4%)	44
Hemolysis	2/39 (5.1%)	2
Cardiac disorders
Palpitations	1/39 (2.6%)	1
Gastrointestinal disorders
Diarrhea	2/39 (5.1%)	2
Ear, nose and throat examination abnormal	1/39 (2.6%)	1
Gastric hemorrhage	1/39 (2.6%)	1
Gastrointestinal disorder	1/39 (2.6%)	1
Gastrointestinal pain	1/39 (2.6%)	1
Ileus	1/39 (2.6%)	1
Mucositis oral	1/39 (2.6%)	1
Nausea	4/39 (10.3%)	4
General disorders
Chills	9/39 (23.1%)	12
Edema limbs	1/39 (2.6%)	2
Fatigue	10/39 (25.6%)	14
Fever	24/39 (61.5%)	40
Hepatobiliary disorders
Cholecystitis	1/39 (2.6%)	1
Hepatobiliary disease	1/39 (2.6%)	1
Immune system disorders
Cytokine release syndrome	1/39 (2.6%)	1
Infections and infestations
Bladder infection	1/39 (2.6%)	1
Bronchitis	1/39 (2.6%)	1
Gingival infection	1/39 (2.6%)	1
Infection	4/39 (10.3%)	6
Mucosal infection	1/39 (2.6%)	1
Opportunistic infection	11/39 (28.2%)	14
Pneumonia	3/39 (7.7%)	7
Sepsis	2/39 (5.1%)	2
Sinusitis	2/39 (5.1%)	4
Skin infection	5/39 (12.8%)	6
Soft tissue infection	1/39 (2.6%)	1
Upper respiratory infection	3/39 (7.7%)	4
Investigations
Alanine aminotransferase increased	1/39 (2.6%)	1
Alkaline phosphatase increased	1/39 (2.6%)	2
Aspartate aminotransferase increased	1/39 (2.6%)	1
Bilirubin increased	2/39 (5.1%)	2
Creatinine increased	1/39 (2.6%)	1
Leukocyte count decreased	30/39 (76.9%)	89
Lymphocyte count decreased	10/39 (25.6%)	31
Neutrophil count decreased	27/39 (69.2%)	58
Platelet count decreased	16/39 (41%)	34
Metabolism and nutrition disorders
Anorexia	2/39 (5.1%)	2
Blood glucose increased	1/39 (2.6%)	1
Blood uric acid increased	1/39 (2.6%)	2
Dehydration	1/39 (2.6%)	1
Serum albumin decreased	1/39 (2.6%)	1
Serum sodium decreased	5/39 (12.8%)	5
Musculoskeletal and connective tissue disorders
Back pain	1/39 (2.6%)	1
Myalgia	2/39 (5.1%)	3
Nervous system disorders
Seizure	1/39 (2.6%)	1
Speech disorder	1/39 (2.6%)	1
Taste alteration	1/39 (2.6%)	1
Renal and urinary disorders
Protein urine positive	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/39 (7.7%)	3
Dyspnea	3/39 (7.7%)	3
Hemorrhage nasal	1/39 (2.6%)	1
Hypoxia	2/39 (5.1%)	2
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/39 (2.6%)	1
Rash desquamating	17/39 (43.6%)	34
Skin disorder	1/39 (2.6%)	1
Sweating	2/39 (5.1%)	2
Vascular disorders
Hypotension	2/39 (5.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.