Ignite Creation Date:
2025-12-24 @ 2:04 PM
Ignite Modification Date:
2025-12-27 @ 9:26 PM
Study NCT ID:
NCT00816595
Status:
COMPLETED
Last Update Posted:
2017-06-15
First Post:
2008-12-31
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Pentostatin, Cyclophosphamide, and Rituximab With or Without Bevacizumab in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Sponsor:
Mayo Clinic
Organization:
Study Overview
Official Title:
Randomized Phase II Trial of Pentostatin, Cyclophosphamide, and Rituximab With or Without Concurrent Avastin® for Previously Untreated B-Chronic Lymphocytic Leukemia (CLL)
Status:
COMPLETED
Status Verified Date:
2017-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
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.
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: