Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
This phase I trial is studying the side effects and the best dose of alvocidib when given together with cyclophosphamide and rituximab in treating patients with high risk B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Alvocidib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can also block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Other find cancer cells and help kill them or carry cancer-killing substances to them. Giving cyclophosphamide, alvocidib, and rituximab together may kill more cancer cells.
B-cell Chronic Lymphocytic Leukemia
Contiguous Stage II Small Lymphocytic Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Stage I Chronic Lymphocytic Leukemia
Stage I Small Lymphocytic Lymphoma
Stage II Chronic Lymphocytic Leukemia
Stage III Chronic Lymphocytic Leukemia
Stage III Small Lymphocytic Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Small Lymphocytic Lymphoma
Other: diagnostic laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Feasibility Trial of Cyclophosphamide, Alvocidib (Flavopiridol) and Rituximab (CAR) in Patients With High Risk B-cell CLL/SLL|
- Treatment related adverse events assessed using the CTEP Active Version of the CTCAE [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
- Maximum-tolerated dose of combination therapy with Cyclophosphamide, Alvocidib, and Rituximab [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]Determined using the CTEP Active Version of the CTCAE.
|Study Start Date:||April 2010|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment (rituximab, cyclophosphamide, alvocidib)
Patients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1).
Other Names:Other: diagnostic laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studiesBiological: rituximab
Other Names:Drug: cyclophosphamide
I. To determine the dose-limiting toxicity and maximum-tolerated dose of treatment with cyclophosphamide, alvocidib, and rituximab in patients with high-risk B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.
II. To determine the feasibility of administering this regimen as an outpatient regimen in these patients.
I. To determine the complete response rate, partial response rate, and minimal-residual disease-negative response rate in patients treated with this regimen.
II. To determine the pharmacokinetics of alvocidib and dexamethasone as part of this regimen.
III. To determine the immunologic effects of this regimen as measured by serial T-cell and NK-cell number, T-cell function, and immunoglobulin levels.
OUTLINE: This is a dose-escalation study of alvocidib.
Patients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for pharmacokinetic and pharmacodynamic studies.
After completion of study treatment, patients are followed up for up to 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01076556
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Joseph Flynn||Ohio State University|