Trial Outcomes & Findings for Pentostatin, Alemtuzumab, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (NCT NCT00669318)
NCT ID: NCT00669318
Last Updated: 2014-07-01
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
41 participants
Primary outcome timeframe
Up to 3 cycles of treatment and 2 cycles of observation (up to 5 months total)
Results posted on
2014-07-01
Participant Flow
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
Participant milestones
| Measure |
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).
|
|---|---|
|
Overall Study
STARTED
|
41
|
|
Overall Study
COMPLETED
|
39
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
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).
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
Baseline Characteristics
Pentostatin, Alemtuzumab, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Baseline characteristics by cohort
| Measure |
Treatment (Pentostatin, Alemtuzumab, Rituximab)
n=39 Participants
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).
|
|---|---|
|
Age, Continuous
|
61 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
39 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Treatment (Pentostatin, Alemtuzumab, Rituximab)
n=39 Participants
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).
|
|---|---|
|
Complete Response Rate
|
10 percentage of participants
Interval 2.9 to 24.2
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Treatment (Pentostatin, Alemtuzumab, Rituximab)
n=39 Participants
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 Response Rate (Complete and Partial Response)
|
56 percentage of patients
Interval 40.0 to 72.0
|
SECONDARY outcome
Timeframe: Follow-up status and retreatment information will be collected up to 5 years from registrationSurvival 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.
Outcome measures
| Measure |
Treatment (Pentostatin, Alemtuzumab, Rituximab)
n=39 Participants
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).
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|---|---|
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Overall Survival
|
34.1 months
Interval 13.6 to
A sufficient number of events has not occurred to accurately estimate the 95% confidence interval.
|
SECONDARY outcome
Timeframe: Follow-up status and retreatment information will be collected up to 5 years from registrationThe 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.
Outcome measures
| Measure |
Treatment (Pentostatin, Alemtuzumab, Rituximab)
n=39 Participants
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).
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|---|---|
|
Progression-free Survival
|
7.2 months
Interval 5.3 to 18.3
|
SECONDARY outcome
Timeframe: Follow-up status and retreatment information will be collected up to 5 years from registrationTime 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
Outcome measures
| Measure |
Treatment (Pentostatin, Alemtuzumab, Rituximab)
n=39 Participants
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).
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|---|---|
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Time to Retreatment
|
9.1 months
Interval 5.7 to 27.0
|
Adverse Events
Treatment (Pentostatin, Alemtuzumab, Rituximab)
Serious events: 4 serious events
Other events: 38 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment (Pentostatin, Alemtuzumab, Rituximab)
n=39 participants at risk
sargramostim
|
|---|---|
|
Infections and infestations
Pneumonia
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Skin infection
|
2.6%
1/39 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
5.1%
2/39 • Number of events 2
|
Other adverse events
| Measure |
Treatment (Pentostatin, Alemtuzumab, Rituximab)
n=39 participants at risk
sargramostim
|
|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
2.6%
1/39 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
2.6%
1/39 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
12.8%
5/39 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.6%
1/39 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.1%
2/39 • Number of events 3
|
|
Nervous system disorders
Seizure
|
2.6%
1/39 • Number of events 1
|
|
Nervous system disorders
Speech disorder
|
2.6%
1/39 • Number of events 1
|
|
Blood and lymphatic system disorders
Blood disorder
|
2.6%
1/39 • Number of events 1
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
7.7%
3/39 • Number of events 3
|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
56.4%
22/39 • Number of events 44
|
|
Blood and lymphatic system disorders
Hemolysis
|
5.1%
2/39 • Number of events 2
|
|
Cardiac disorders
Palpitations
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
5.1%
2/39 • Number of events 2
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Ileus
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis oral
|
2.6%
1/39 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
10.3%
4/39 • Number of events 4
|
|
General disorders
Chills
|
23.1%
9/39 • Number of events 12
|
|
General disorders
Edema limbs
|
2.6%
1/39 • Number of events 2
|
|
General disorders
Fatigue
|
25.6%
10/39 • Number of events 14
|
|
General disorders
Fever
|
61.5%
24/39 • Number of events 40
|
|
Hepatobiliary disorders
Cholecystitis
|
2.6%
1/39 • Number of events 1
|
|
Hepatobiliary disorders
Hepatobiliary disease
|
2.6%
1/39 • Number of events 1
|
|
Immune system disorders
Cytokine release syndrome
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Bladder infection
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Bronchitis
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Gingival infection
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Infection
|
10.3%
4/39 • Number of events 6
|
|
Infections and infestations
Mucosal infection
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Opportunistic infection
|
28.2%
11/39 • Number of events 14
|
|
Infections and infestations
Pneumonia
|
7.7%
3/39 • Number of events 7
|
|
Infections and infestations
Sepsis
|
5.1%
2/39 • Number of events 2
|
|
Infections and infestations
Sinusitis
|
5.1%
2/39 • Number of events 4
|
|
Infections and infestations
Skin infection
|
12.8%
5/39 • Number of events 6
|
|
Infections and infestations
Soft tissue infection
|
2.6%
1/39 • Number of events 1
|
|
Infections and infestations
Upper respiratory infection
|
7.7%
3/39 • Number of events 4
|
|
Investigations
Alanine aminotransferase increased
|
2.6%
1/39 • Number of events 1
|
|
Investigations
Alkaline phosphatase increased
|
2.6%
1/39 • Number of events 2
|
|
Investigations
Aspartate aminotransferase increased
|
2.6%
1/39 • Number of events 1
|
|
Investigations
Bilirubin increased
|
5.1%
2/39 • Number of events 2
|
|
Investigations
Creatinine increased
|
2.6%
1/39 • Number of events 1
|
|
Investigations
Leukocyte count decreased
|
76.9%
30/39 • Number of events 89
|
|
Investigations
Lymphocyte count decreased
|
25.6%
10/39 • Number of events 31
|
|
Investigations
Neutrophil count decreased
|
69.2%
27/39 • Number of events 58
|
|
Investigations
Platelet count decreased
|
41.0%
16/39 • Number of events 34
|
|
Metabolism and nutrition disorders
Anorexia
|
5.1%
2/39 • Number of events 2
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
2.6%
1/39 • Number of events 1
|
|
Metabolism and nutrition disorders
Blood uric acid increased
|
2.6%
1/39 • Number of events 2
|
|
Nervous system disorders
Taste alteration
|
2.6%
1/39 • Number of events 1
|
|
Renal and urinary disorders
Protein urine positive
|
2.6%
1/39 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.7%
3/39 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.7%
3/39 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage nasal
|
2.6%
1/39 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.1%
2/39 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
2.6%
1/39 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
43.6%
17/39 • Number of events 34
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
2.6%
1/39 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Sweating
|
5.1%
2/39 • Number of events 2
|
|
Vascular disorders
Hypotension
|
5.1%
2/39 • Number of events 2
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place