Leukemia, Lymphoma
Conditions
Keywords
B-cell chronic lymphocytic leukemia, stage I small lymphocytic lymphoma, stage II small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia
Brief summary
RATIONALE: Pentostatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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. Monoclonal antibodies, such as 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 cyclophosphamide and rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying the side effects and how well giving pentostatin together with cyclophosphamide and rituximab works in treating patients with previously untreated chronic lymphocytic leukemia.
Detailed description
OBJECTIVES: * To determine the frequency of response in patients with previously untreated, intermediate- or high-risk B-cell chronic lymphocytic leukemia (CLL) treated with pentostatin, cyclophosphamide, and rituximab. * To characterize the toxicity of this regimen in these patients. OUTLINE: Patients receive cyclophosphamide IV followed by pentostatin IV on day 1 in course 1. Beginning in course 2 and in all subsequent courses, patients receive cyclophosphamide IV on day 1, pentostatin IV on day 1, and rituximab IV on day 1 or on days 1 and 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at least every 3 months for 1 year.
Interventions
BIOLOGICALrituximab
DRUGcyclophosphamide
DRUGpentostatin
Sponsors
National Cancer Institute (NCI)
Astex Pharmaceuticals, Inc.
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of chronic lymphocytic leukemia (CLL), as evidenced by an absolute lymphocytosis in the blood of at least 5,000 lymphocytes per microliter OR bone marrow lymphocytosis ≥ 30% of all nucleated cells * Previously untreated disease * Meets 1 of the following risk criteria as defined by the three-stage Rai system * Intermediate-risk disease * Must meet the criteria for active disease as defined by the NCI Working Group guidelines including the following: * Weight loss * Fatigue * Fevers * Evidence of progressive marrow failure * Splenomegaly * Progressive lymphadenopathy * Progressive lymphocytosis with a rapid doubling time * High-risk disease * Malignant lymphocytes must demonstrate B-cells via immunophenotypic or immunohistochemical analysis * Patients with small lymphocytic lymphoma (CLL type) are eligible PATIENT CHARACTERISTICS: Inclusion criteria: * Karnofsky performance status 60-100% * Total bilirubin ≤ 2.0 mg/dL (patients with Gilbert disease or autoimmune hemolytic anemia should have an evaluation for other causes of hyperbilirubinemia, but if none are found they may be enrolled regardless of serum bilirubin) * Total creatinine ≤ 2.0 mg/dL OR creatinine clearance \> 50 mL/min * Not pregnant or nursing * Fertile patients must use effective contraception * Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia are eligible for treatment on this protocol regardless of disease stage
Exclusion criteria
* Significant active infections * Ongoing hepatitis B infection, specifically hepatitis B antigen or surface antigen positivity * Patients who are hepatitis B antibody positive are eligible for this protocol PRIOR CONCURRENT THERAPY: * Concurrent prednisone allowed provided it is used as brief courses (≤ 7 days) for inflammatory conditions unrelated to CLL * No prior cytotoxic therapy or rituximab for this cancer * No concurrent radiotherapy or other chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Objective Response | 2 years | The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Radiographic studies are not required but those that were abnormal pre-treatment, will be repeated to document the degree of maximal response. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Patients All patients who received cyclophosphamide, pentostatin and rituximab | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Non-Compliance | 3 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 18 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 49 / 49 |
| serious Total, serious adverse events | 18 / 49 |
Outcome results
Primary
Overall Objective Response
The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Radiographic studies are not required but those that were abnormal pre-treatment, will be repeated to document the degree of maximal response.
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Patients | Overall Objective Response | Complete Response (CR) | 10 Participants |
| All Patients | Overall Objective Response | Nodular Response | 5 Participants |
| All Patients | Overall Objective Response | Partial Response (PR) | 26 Participants |
| All Patients | Overall Objective Response | Stable Disease (SD) | 4 Participants |
| All Patients | Overall Objective Response | Progression of Disease (POD) | 1 Participants |