Pentostatin, Cyclophosphamide, and Rituximab With or Without Bevacizumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Study Details
Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as pentostatin and cyclophosphamide, 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 rituximab and bevacizumab, 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. It is not yet known whether giving pentostatin and cyclophosphamide together with rituximab is more effective with or without bevacizumab in treating patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.
PURPOSE: This randomized phase II trial is studying the side effects of giving pentostatin and cyclophosphamide together with rituximab with or without bevacizumab and to see how well it works in treating patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
Primary
-
To assess the rate of complete and overall response in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma treated with pentostatin, cyclophosphamide, and rituximab with or without bevacizumab.
-
To assess the proportion of patients who achieve a negative minimal residual disease state after treatment with these regimens.
-
To monitor and assess the adverse events of these regimens.
Secondary
-
To determine if molecular prognostic parameters (ZAP-70, CD38, cytogenetic abnormalities identified by FISH, and IgVH mutation status) relate to response in these patients.
-
To determine the progression-free survival of patients treated with these regimens.
-
To complete additional correlative studies to gain insight into disease biology and how it influences drug sensitivity.
OUTLINE: Patients are stratified according to Rai risk group (high [Rai stage III or IV] vs low [Rai stage 0] or intermediate [Rai stage I or II]) and FISH prognosis group (favorable [normal, +12, 13q-, or other] vs unfavorable [17p- or 11q-]). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 1 of courses 1-5 and on days 1, 22, and 43 of course 6; rituximab IV over 2-4 hours on days 2 and 3 of course 1 and on day 1 of courses 2-6; and pentostatin IV over 30 minutes and cyclophosphamide IV over 30 minutes on day 2 of course 1 and on day 1 of courses 2-6. Patients also receive pegfilgrastim subcutaneously (SC) on day 3 of course 1 and on day 2 of courses 2-6. Treatment repeats every 21 days* for 6 courses in the absence of disease progression or unacceptable toxicity.
NOTE: *Course 6 is 56 days in duration
- Arm II: Patients receive rituximab IV over 2-4 hours on days 1 and 2 of course 1 and on day 1 of courses 2-6 and pentostatin IV over 30 minutes and cyclophosphamide IV over 30 minutes on day 1. Patients also receive pegfilgrastim SC on day 2. Treatment repeats every 21 days* for 6 courses in the absence of disease progression or unacceptable toxicity.
NOTE: *Course 6 is 56 days in duration
Patients undergo blood sample collection and bone marrow biopsy/aspiration periodically for translational research studies. Samples are analyzed by flow cytometry for assessment of minimal residual disease. Molecular prognostic markers (including CD38, ZAP-70, IgVH gene mutation status, and cytogenetic abnormalities by FISH), Tcl-1 and CD49d protein expression, and immunoglobulin heavy chain D and J family gene usage are also analyzed. Plasma samples are stored for future studies evaluating levels of VEGF, bFGF, and thrombospondin by ELISA.
After completion of study therapy, patients are followed periodically for up to 5 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin Patients receive 15 mg/kg bevacizumab IV over 30-90 minutes on day 1 of courses 1-5 and on days 1, 22, and 43 of course 6; 375 mg/m^2 rituximab IV over 2-4 hours on days 2 and 3 of course 1 and on day 1 of courses 2-6; and 2 mg/m^3 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 2 of course 1 and on day 1 of courses 2-6. Patients also receive 6 mg pegfilgrastim subcutaneously (SC) on day 3 of course 1 and on day 2 of courses 2-6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. |
Biological: bevacizumab
Given IV
Other Names:
Biological: pegfilgrastim
Given subcutaneously
Biological: rituximab
Given IV
Drug: cyclophosphamide
Given IV
Drug: pentostatin
Given IV
|
| Experimental: Arm B: Pentostatin, Cyclophosphamide, and Rituximab Patients receive 100 mg rituximab IV over 2-4 hours on day 1 and 375 mg/m^2 on day 2 of course 1 and 375 mg/m^2 on day 1 of courses 2-6. They receive 2 mg/m^2 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 1. Patients also receive 6 mg pegfilgrastim SC on day 2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. |
Biological: pegfilgrastim
Given subcutaneously
Biological: rituximab
Given IV
Drug: cyclophosphamide
Given IV
Drug: pentostatin
Given IV
|
Outcome Measures
Primary Outcome Measures
- Complete and Overall Response Rate [Evaluated after 6 cycles (up to 196 days)]
A Complete Response (CR) requires all of the following for 2 months: Absence of lymphadenopathy by physical examination (PE) No hepato- or splenomegaly by PE Neutrophils >1500/ul, Platelets >100,000/ul. Hemoglobin >11.0 gm/dl, Peripheral blood lymphocytes <4000/uL Nodular Partial Response (nPR) is defined as a patient qualified for a CR, but regenerative nodules are histologically present on bone marrow samples. A Clinical Complete Response (CCR) is defined as a patient qualified for a CR, but bone marrow samples are not available. A Partial Response (PR) requires 50% reduction in 2 of the following: peripheral blood lymphocytes, or the sum of the products of the maximal perpendicular diameters, or the size of liver and/or spleen; and a 50% increase in neutrophils, platelets, or hemoglobin. Overall response rate is calculated as the number of patients receiving CR, CCR, nPR, or PR as their objective status divided by the total number of evaluable patients.
Secondary Outcome Measures
- Overall Survival [Assessed up to 5 years from registration]
The Kaplan-Meier method will be used to estimate overall survival distributions Overall survival is measured as the time from registration to the time of death due to any cause.
- Progression-free Survival [Assessed up to 5 years from registration]
The Kaplan-Meier method will be used to estimate progression-free survival distribution. Progression-free survival is defined as the time from registration to the time of progression or death, whichever occurs first.
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Diagnosis of 1 of the following:
-
Biopsy proven small lymphocytic lymphoma (SLL)
-
Chronic lymphocytic leukemia (CLL)* as evidenced by the following criteria:
-
Peripheral blood lymphocyte count > 5,000/mm³ consisting of small to moderate size lymphocytes
-
Immunophenotyping consistent with CLL, defined by the following:
-
The predominant population of lymphocytes share both B-cell antigens (CD19, CD20, or CD23) as well as CD-5 in the absence of other pan-T-cell markers (CD-3 or CD-2)
-
Dim surface immunoglobulin expression
-
Exclusively kappa and lambda light chains
-
Negative FISH analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy samples NOTE: *Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL
-
Has ≥ 1 of the following indications** for chemotherapy:
-
Evidence of progressive marrow failure as manifested by the development of or worsening anemia (hemoglobin ≤ 11 g/dL) and/or thrombocytopenia (platelet count ≤ 100,000/mm³)
-
Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly
-
Has ≥ 1 of the following disease-related symptoms:
-
Weight loss > 10% within the past 6 months
-
Extreme fatigue attributed to CLL
-
Fevers > 100.5^oF for 2 weeks without evidence of infection
-
Night sweats without evidence of infection
-
Progressive lymphocytosis (not due to the effects of corticosteroids) with an increase of > 50% over a 2-month period or an anticipated doubling time of < 6 months NOTE: **Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not sufficient indications for study treatment
PATIENT CHARACTERISTICS:
-
Eastern Cooperative Oncology Group performance status 0-3
-
Life expectancy ≥ 12 months
-
Total bilirubin ≤ 3.0 times upper limit of normal (ULN) (unless due to Gilbert's disease)
-
Direct bilirubin < 1.5 mg/dL (in patients with Gilbert's disease)
-
Serum glutamate oxaloacetate transaminase ≤ 3.0 times ULN (unless due to hepatic involvement by CLL)
-
Creatinine ≤ 1.5 times ULN
-
Urine protein:creatinine ratio < 1.0 OR < 1 g of protein by 24-hour urine collection
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception during and for 12 months after completion of study treatment
-
Willing to provide mandatory blood and tissue samples
-
None of the following cardiovascular conditions:
-
NYHA class III-IV heart disease
-
Myocardial infarction within the past 6 months
-
Unstable angina
-
Stroke, cerebrovascular accident, or transient ischemic attack within the past 6 months
-
Arterial thromboembolic events within the past 12 months
-
Clinically significant peripheral vascular disease
-
Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg
-
Hypertension allowed provided it is controlled with a stable anti-hypertensive regimen
-
History of hypertensive crises or hypertensive encephalopathy
-
Deep venous thromboses or pulmonary embolism within the past 12 months
-
No evidence of bleeding diathesis or coagulopathy
-
No uncontrolled or active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment
-
No active or recent history (within the past 30 days) of hemoptysis (≥ ½ teaspoon of bright red blood per episode)
-
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
-
No active peptic ulcer disease
-
No serious non-healing wound, ulcer, or bone fracture
-
No significant traumatic injury within the past 28 days
-
No uncontrolled infection
-
No active HIV infection
-
No other active primary malignancy (except nonmelanoma skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting survival to ≤ 2 years
-
No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude study participation
PRIOR CONCURRENT THERAPY:
-
Prior corticosteroids allowed
-
More than 4 weeks since prior radiotherapy
-
More than 28 days since prior and no concurrent major surgical procedure or open biopsy
-
More than 7 days since prior minor surgical procedure, fine needle aspiration, or core biopsy (other than bone marrow biopsy)
-
No concurrent therapeutic doses of coumadin-derivative anticoagulants (e.g., warfarin)
-
Doses of ≤ 2 mg daily allowed for prophylaxis of thrombosis
-
Prophylactic doses of low molecular weight heparin allowed
-
No other concurrent investigational agents for treatment of CLL or SLL
-
No other concurrent specific anticancer treatment except hormonal therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic in Arizona | Scottsdale | Arizona | United States | 85259 |
| 2 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
Sponsors and Collaborators
- Mayo Clinic
- National Cancer Institute (NCI)
Investigators
- Study Chair: Tait D. Shanafelt, MD, Mayo Clinic
- Principal Investigator: Jose F. Francisco, M.D., Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000630491
- P30CA015083
- RC0783
- 08-002080
- AVF4491s
- NCI-2009-01225
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin | Arm B: Pentostatin, Cyclophosphamide, and Rituximab |
|---|---|---|
| Arm/Group Description | Patients receive 15 mg/kg bevacizumab IV over 30-90 minutes on day 1 of courses 1-5 and on days 1, 22, and 43 of course 6; 375 mg/m^2 rituximab IV over 2-4 hours on days 2 and 3 of course 1 and on day 1 of courses 2-6; and 2 mg/m^3 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 2 of course 1 and on day 1 of courses 2-6. Patients also receive 6 mg pegfilgrastim subcutaneously (SC) on day 3 of course 1 and on day 2 of courses 2-6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. bevacizumab: Given IV pegfilgrastim: Given subcutaneously rituximab: Given IV cyclophosphamide: Given IV pentostatin: Given IV | Patients receive 100 mg rituximab IV over 2-4 hours on day 1 and 375 mg/m^2 on day 2 of course 1 and 375 mg/m^2 on day 1 of courses 2-6. They receive 2 mg/m^2 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 1. Patients also receive 6 mg pegfilgrastim SC on day 2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. pegfilgrastim: Given subcutaneously rituximab: Given IV cyclophosphamide: Given IV pentostatin: Given IV |
| Period Title: Overall Study | ||
| STARTED | 35 | 33 |
| COMPLETED | 33 | 33 |
| NOT COMPLETED | 2 | 0 |
Baseline Characteristics
| Arm/Group Title | Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin | Arm B: Pentostatin, Cyclophosphamide, and Rituximab | Total |
|---|---|---|---|
| Arm/Group Description | Patients receive 15 mg/kg bevacizumab IV over 30-90 minutes on day 1 of courses 1-5 and on days 1, 22, and 43 of course 6; 375 mg/m^2 rituximab IV over 2-4 hours on days 2 and 3 of course 1 and on day 1 of courses 2-6; and 2 mg/m^3 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 2 of course 1 and on day 1 of courses 2-6. Patients also receive 6 mg pegfilgrastim subcutaneously (SC) on day 3 of course 1 and on day 2 of courses 2-6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. | Patients receive 100 mg rituximab IV over 2-4 hours on day 1 and 375 mg/m^2 on day 2 of course 1 and 375 mg/m^2 on day 1 of courses 2-6. They receive 2 mg/m^2 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 1. Patients also receive 6 mg pegfilgrastim SC on day 2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. | Total of all reporting groups |
| Overall Participants | 33 | 33 | 66 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
65
|
63
|
63.5
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
13
39.4%
|
9
27.3%
|
22
33.3%
|
| Male |
20
60.6%
|
24
72.7%
|
44
66.7%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
33
100%
|
33
100%
|
66
100%
|
Outcome Measures
| Title | Complete and Overall Response Rate |
|---|---|
| Description | A Complete Response (CR) requires all of the following for 2 months: Absence of lymphadenopathy by physical examination (PE) No hepato- or splenomegaly by PE Neutrophils >1500/ul, Platelets >100,000/ul. Hemoglobin >11.0 gm/dl, Peripheral blood lymphocytes <4000/uL Nodular Partial Response (nPR) is defined as a patient qualified for a CR, but regenerative nodules are histologically present on bone marrow samples. A Clinical Complete Response (CCR) is defined as a patient qualified for a CR, but bone marrow samples are not available. A Partial Response (PR) requires 50% reduction in 2 of the following: peripheral blood lymphocytes, or the sum of the products of the maximal perpendicular diameters, or the size of liver and/or spleen; and a 50% increase in neutrophils, platelets, or hemoglobin. Overall response rate is calculated as the number of patients receiving CR, CCR, nPR, or PR as their objective status divided by the total number of evaluable patients. |
| Time Frame | Evaluated after 6 cycles (up to 196 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| One patient on Arm A was treated at an incorrect dose level and was not evaluable for this endpoint. On Arm B, one patient did not have correct eligibility reported, one patient did not complete an assessment, and one patient was incorrectly treated. The primary endpoint is based on 32 Arm A and 30 Arm B patients. |
| Arm/Group Title | Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin | Arm B: Pentostatin, Cyclophosphamide, and Rituximab |
|---|---|---|
| Arm/Group Description | Patients receive 15 mg/kg bevacizumab IV over 30-90 minutes on day 1 of courses 1-5 and on days 1, 22, and 43 of course 6; 375 mg/m^2 rituximab IV over 2-4 hours on days 2 and 3 of course 1 and on day 1 of courses 2-6; and 2 mg/m^3 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 2 of course 1 and on day 1 of courses 2-6. Patients also receive 6 mg pegfilgrastim subcutaneously (SC) on day 3 of course 1 and on day 2 of courses 2-6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. | Patients receive 100 mg rituximab IV over 2-4 hours on day 1 and 375 mg/m^2 on day 2 of course 1 and 375 mg/m^2 on day 1 of courses 2-6. They receive 2 mg/m^2 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 1. Patients also receive 6 mg pegfilgrastim SC on day 2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. |
| Measure Participants | 32 | 30 |
| Complete Response (CR) Rate |
50.0
|
33.3
|
| Overall Response Rate |
93.8
|
96.7
|
| Title | Overall Survival |
|---|---|
| Description | The Kaplan-Meier method will be used to estimate overall survival distributions Overall survival is measured as the time from registration to the time of death due to any cause. |
| Time Frame | Assessed up to 5 years from registration |
Outcome Measure Data
| Analysis Population Description |
|---|
| One patient on Arm A was treated at an incorrect dose level and was not evaluable for this endpoint. On Arm B, one patient did not have correct eligibility reported, one patient did not complete an assessment, and one patient was incorrectly treated. The primary endpoint is based on 32 Arm A and 30 Arm B patients. |
| Arm/Group Title | Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin | Arm B: Pentostatin, Cyclophosphamide, and Rituximab |
|---|---|---|
| Arm/Group Description | Patients receive 15 mg/kg bevacizumab IV over 30-90 minutes on day 1 of courses 1-5 and on days 1, 22, and 43 of course 6; 375 mg/m^2 rituximab IV over 2-4 hours on days 2 and 3 of course 1 and on day 1 of courses 2-6; and 2 mg/m^3 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 2 of course 1 and on day 1 of courses 2-6. Patients also receive 6 mg pegfilgrastim subcutaneously (SC) on day 3 of course 1 and on day 2 of courses 2-6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. | Patients receive 100 mg rituximab IV over 2-4 hours on day 1 and 375 mg/m^2 on day 2 of course 1 and 375 mg/m^2 on day 1 of courses 2-6. They receive 2 mg/m^2 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 1. Patients also receive 6 mg pegfilgrastim SC on day 2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. |
| Measure Participants | 32 | 30 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
| Title | Progression-free Survival |
|---|---|
| Description | The Kaplan-Meier method will be used to estimate progression-free survival distribution. Progression-free survival is defined as the time from registration to the time of progression or death, whichever occurs first. |
| Time Frame | Assessed up to 5 years from registration |
Outcome Measure Data
| Analysis Population Description |
|---|
| One patient on Arm A was treated at an incorrect dose level and was not evaluable for this endpoint. On Arm B, one patient did not have correct eligibility reported, one patient did not complete an assessment, and one patient was incorrectly treated. The primary endpoint is based on 32 Arm A and 30 Arm B patients. |
| Arm/Group Title | Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin | Arm B: Pentostatin, Cyclophosphamide, and Rituximab |
|---|---|---|
| Arm/Group Description | Patients receive 15 mg/kg bevacizumab IV over 30-90 minutes on day 1 of courses 1-5 and on days 1, 22, and 43 of course 6; 375 mg/m^2 rituximab IV over 2-4 hours on days 2 and 3 of course 1 and on day 1 of courses 2-6; and 2 mg/m^3 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 2 of course 1 and on day 1 of courses 2-6. Patients also receive 6 mg pegfilgrastim subcutaneously (SC) on day 3 of course 1 and on day 2 of courses 2-6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. bevacizumab: Given IV pegfilgrastim: Given subcutaneously rituximab: Given IV cyclophosphamide: Given IV pentostatin: Given IV | Patients receive 100 mg rituximab IV over 2-4 hours on day 1 and 375 mg/m^2 on day 2 of course 1 and 375 mg/m^2 on day 1 of courses 2-6. They receive 2 mg/m^2 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 1. Patients also receive 6 mg pegfilgrastim SC on day 2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. pegfilgrastim: Given subcutaneously rituximab: Given IV cyclophosphamide: Given IV pentostatin: Given IV |
| Measure Participants | 32 | 30 |
| Median (95% Confidence Interval) [months] |
NA
|
34.1
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin | Arm B: Pentostatin, Cyclophosphamide, and Rituximab | ||
| Arm/Group Description | Patients receive 15 mg/kg bevacizumab IV over 30-90 minutes on day 1 of courses 1-5 and on days 1, 22, and 43 of course 6; 375 mg/m^2 rituximab IV over 2-4 hours on days 2 and 3 of course 1 and on day 1 of courses 2-6; and 2 mg/m^3 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 2 of course 1 and on day 1 of courses 2-6. Patients also receive 6 mg pegfilgrastim subcutaneously (SC) on day 3 of course 1 and on day 2 of courses 2-6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. bevacizumab: Given IV pegfilgrastim: Given subcutaneously rituximab: Given IV cyclophosphamide: Given IV pentostatin: Given IV | Patients receive 100 mg rituximab IV over 2-4 hours on day 1 and 375 mg/m^2 on day 2 of course 1 and 375 mg/m^2 on day 1 of courses 2-6. They receive 2 mg/m^2 pentostatin IV over 30 minutes and 600 mg/m^2 cyclophosphamide IV over 30 minutes on day 1. Patients also receive 6 mg pegfilgrastim SC on day 2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. pegfilgrastim: Given subcutaneously rituximab: Given IV cyclophosphamide: Given IV pentostatin: Given IV | ||
All Cause Mortality |
||||
| Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin | Arm B: Pentostatin, Cyclophosphamide, and Rituximab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin | Arm B: Pentostatin, Cyclophosphamide, and Rituximab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/33 (33.3%) | 5/33 (15.2%) | ||
| Cardiac disorders | ||||
| Left ventricular dysfunction | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Left ventricular failure | 2/33 (6.1%) | 2 | 0/33 (0%) | 0 |
| Myocardial ischemia | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Myocarditis | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Nausea | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| General disorders | ||||
| Chills | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Edema limbs | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Fatigue | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Fever | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Localized edema | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Infections and infestations | ||||
| Pneumonia | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Sepsis | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Investigations | ||||
| Creatinine increased | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Neutrophil count decreased | 4/33 (12.1%) | 5 | 2/33 (6.1%) | 2 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Nervous system disorders | ||||
| Neurological disorder NOS | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Psychiatric disorders | ||||
| Confusion | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Renal and urinary disorders | ||||
| Bladder hemorrhage | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Bladder pain | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Cystitis | 2/33 (6.1%) | 2 | 0/33 (0%) | 0 |
| Protein urine positive | 2/33 (6.1%) | 2 | 0/33 (0%) | 0 |
| Renal failure | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 2/33 (6.1%) | 2 | 0/33 (0%) | 0 |
| Dyspnea | 3/33 (9.1%) | 3 | 0/33 (0%) | 0 |
| Pneumonitis | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Pulmonary hypertension | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Vascular disorders | ||||
| Hypertension | 2/33 (6.1%) | 2 | 0/33 (0%) | 0 |
| Vascular disorder | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Arm A: Pentostatin, Cyclophosphamide, Rituximab, and Avastin | Arm B: Pentostatin, Cyclophosphamide, and Rituximab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 32/33 (97%) | 30/33 (90.9%) | ||
| Blood and lymphatic system disorders | ||||
| Blood disorder | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Hemoglobin decreased | 13/33 (39.4%) | 52 | 16/33 (48.5%) | 24 |
| Cardiac disorders | ||||
| Cardiac disorder | 2/33 (6.1%) | 4 | 0/33 (0%) | 0 |
| Left ventricular failure | 1/33 (3%) | 2 | 0/33 (0%) | 0 |
| Myocardial ischemia | 1/33 (3%) | 1 | 1/33 (3%) | 1 |
| Restrictive cardiomyopathy | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Supraventricular tachycardia | 0/33 (0%) | 0 | 1/33 (3%) | 2 |
| Torsade de pointes | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Ventricular tachycardia | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Endocrine disorders | ||||
| Hyperthyroidism | 2/33 (6.1%) | 2 | 0/33 (0%) | 0 |
| Hypothyroidism | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 4/33 (12.1%) | 7 | 6/33 (18.2%) | 8 |
| Ascites | 2/33 (6.1%) | 2 | 0/33 (0%) | 0 |
| Diarrhea | 3/33 (9.1%) | 3 | 1/33 (3%) | 2 |
| Ear, nose and throat examination abnormal | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Mucositis oral | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Nausea | 9/33 (27.3%) | 16 | 10/33 (30.3%) | 17 |
| Rectal pain | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Vomiting | 7/33 (21.2%) | 12 | 6/33 (18.2%) | 11 |
| General disorders | ||||
| Chest pain | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Death | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Edema limbs | 1/33 (3%) | 1 | 1/33 (3%) | 1 |
| Fatigue | 31/33 (93.9%) | 214 | 29/33 (87.9%) | 152 |
| Fever | 8/33 (24.2%) | 10 | 13/33 (39.4%) | 26 |
| Hypothermia | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Hepatobiliary disorders | ||||
| Cholecystitis | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Immune system disorders | ||||
| Cytokine release syndrome | 1/33 (3%) | 1 | 2/33 (6.1%) | 4 |
| Hypersensitivity | 1/33 (3%) | 1 | 1/33 (3%) | 1 |
| Immune system disorder | 1/33 (3%) | 2 | 0/33 (0%) | 0 |
| Infections and infestations | ||||
| Bronchitis | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Gallbladder infection | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Infection | 0/33 (0%) | 0 | 2/33 (6.1%) | 2 |
| Pharyngitis | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Pneumonia | 3/33 (9.1%) | 5 | 3/33 (9.1%) | 4 |
| Sepsis | 2/33 (6.1%) | 3 | 3/33 (9.1%) | 4 |
| Sinusitis | 2/33 (6.1%) | 2 | 1/33 (3%) | 2 |
| Upper aerodigestive tract infection | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Upper respiratory infection | 3/33 (9.1%) | 4 | 6/33 (18.2%) | 9 |
| Urinary tract infection | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Wound infection | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Investigations | ||||
| Creatinine increased | 10/33 (30.3%) | 28 | 11/33 (33.3%) | 40 |
| Neutrophil count decreased | 18/33 (54.5%) | 26 | 17/33 (51.5%) | 36 |
| Platelet count decreased | 21/33 (63.6%) | 79 | 14/33 (42.4%) | 60 |
| Weight loss | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 5/33 (15.2%) | 9 | 1/33 (3%) | 3 |
| Blood glucose increased | 1/33 (3%) | 1 | 5/33 (15.2%) | 10 |
| Dehydration | 2/33 (6.1%) | 2 | 1/33 (3%) | 1 |
| Serum albumin decreased | 1/33 (3%) | 1 | 1/33 (3%) | 1 |
| Serum calcium decreased | 1/33 (3%) | 1 | 3/33 (9.1%) | 3 |
| Serum sodium decreased | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Serum sodium increased | 1/33 (3%) | 2 | 0/33 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthritis | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Back pain | 1/33 (3%) | 1 | 1/33 (3%) | 1 |
| Joint pain | 1/33 (3%) | 2 | 0/33 (0%) | 0 |
| Pain in extremity | 0/33 (0%) | 0 | 1/33 (3%) | 2 |
| Nervous system disorders | ||||
| Depressed level of consciousness | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Encephalopathy | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Extrapyramidal disorder | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Headache | 19/33 (57.6%) | 48 | 11/33 (33.3%) | 23 |
| Neuralgia | 1/33 (3%) | 1 | 1/33 (3%) | 1 |
| Peripheral motor neuropathy | 1/33 (3%) | 1 | 1/33 (3%) | 1 |
| Peripheral sensory neuropathy | 1/33 (3%) | 2 | 1/33 (3%) | 1 |
| Syncope vasovagal | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Tremor | 0/33 (0%) | 0 | 1/33 (3%) | 5 |
| Psychiatric disorders | ||||
| Agitation | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Depression | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Insomnia | 1/33 (3%) | 4 | 1/33 (3%) | 4 |
| Renal and urinary disorders | ||||
| Cystitis | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Hemorrhage urinary tract | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Protein urine positive | 12/33 (36.4%) | 22 | 3/33 (9.1%) | 3 |
| Renal failure | 1/33 (3%) | 2 | 0/33 (0%) | 0 |
| Urinary frequency | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Urinary incontinence | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Allergic rhinitis | 0/33 (0%) | 0 | 1/33 (3%) | 2 |
| Cough | 1/33 (3%) | 1 | 2/33 (6.1%) | 3 |
| Dyspnea | 1/33 (3%) | 1 | 3/33 (9.1%) | 4 |
| Hypoxia | 1/33 (3%) | 1 | 1/33 (3%) | 1 |
| Pleural effusion | 3/33 (9.1%) | 3 | 0/33 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 1/33 (3%) | 2 | 0/33 (0%) | 0 |
| Dry skin | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Erythema multiforme | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Rash acneiform | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Rash desquamating | 4/33 (12.1%) | 6 | 2/33 (6.1%) | 2 |
| Skin disorder | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Sweating | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
| Vascular disorders | ||||
| Flushing | 0/33 (0%) | 0 | 1/33 (3%) | 2 |
| Hot flashes | 1/33 (3%) | 2 | 0/33 (0%) | 0 |
| Hypertension | 17/33 (51.5%) | 52 | 9/33 (27.3%) | 19 |
| Hypotension | 0/33 (0%) | 0 | 2/33 (6.1%) | 2 |
| Thrombosis | 0/33 (0%) | 0 | 1/33 (3%) | 1 |
| Vascular disorder | 1/33 (3%) | 1 | 0/33 (0%) | 0 |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Tait Shanafelt, M.D. |
|---|---|
| Organization | Mayo Clinic |
| Phone | |
| shanafelt.tait@mayo.edu |
- CDR0000630491
- P30CA015083
- RC0783
- 08-002080
- AVF4491s
- NCI-2009-01225