Leukemia, Lymphoma
Conditions
Keywords
stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, B-cell chronic lymphocytic leukemia, splenic marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, Waldenstrom macroglobulinemia, prolymphocytic leukemia, stage I marginal zone lymphoma, contiguous stage II adult diffuse small cleaved cell lymphoma, contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, contiguous stage II mantle cell lymphoma, contiguous stage II marginal zone lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage III marginal zone lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, refractory chronic lymphocytic leukemia, stage IV marginal zone lymphoma
Brief summary
RATIONALE: 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. 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. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving rituximab and cyclophosphamide together with pegfilgrastim may be effective in treating leukemia or non-Hodgkin's lymphoma. PURPOSE: This phase II trial is studying how well giving rituximab and cyclophosphamide together with pegfilgrastim works in treating patients with B-cell leukemia, low-grade non-Hodgkin's lymphoma, or mantle cell lymphoma.
Detailed description
OBJECTIVES: * Determine the safety of high-dose cyclophosphamide, rituximab, and pegfilgrastim in patients with B-cell leukemia or low-grade or mantle cell lymphoma. * Determine the molecular response rate in patients treated with this regimen. OUTLINE: This is an open-label study. Patients receive rituximab IV over 30-60 minutes on days 1, 4, 8,11, 45, and 52, cyclophosphamide IV over 1 hour on days 15-18, and pegfilgrastim subcutaneously on day 19 or 20 in the absence of unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study.
Interventions
BIOLOGICALPegfilgrastim
6 mg SQ 24-48 hours after last dose of cyclophosphamide.
BIOLOGICALRituximab
375 mg/m\^2/day on Days 1, 4, 8, 11, 45, and 52.
DRUGCyclophosphamide
50 mg/kg/day on Days 15, 16, 17, and 18.
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * One of the following B-cell leukemias or lymphomas, as defined by World Health Organization criteria: * Chronic lymphocytic leukemia/small lymphocytic lymphoma * B-cell prolymphocytic leukemia * Lymphoplasmacytic leukemia * Marginal zone lymphoma (splenic, extranodal, or nodal) * Follicular lymphoma (grade 1 or 2) * Mantle cell lymphoma * No more than minimal (approximately 10%) morphologically identifiable cancer cells on bone marrow biopsy * When cancer cells are morphologically difficult to distinguish from normal cells, flow cytometry must show no more than 10% identifiable cancer cells * Must have received ≤ 12 months of prior cytotoxic therapy, achieving at least a partial response NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of indolent or aggressive lymphoma will replace the former terminology of low, intermediate, or high grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * WBC ≥ 3,000/mm\^3 * Hemoglobin ≥ 10.0 g/dL * Platelet count ≥ 75,000/mm\^3 * Serum creatinine ≤ 2.0 mg/dL * Total bilirubin ≤ 2 mg/dL unless secondary to tumor * AST or ALT \< 2 times upper limit of normal * Normal (≥ 45%) left ventricular cardiac ejection fraction (determined by echocardiogram or MUGA scan) * DLCO \> 50% predicted * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No known sensitivity to E. coli-derived products (e.g. filgrastim \[G-CSF\], insulin, asparaginase, growth hormone, or recombinant interferon alfa-2b) or any treatment study drugs * No active infections requiring oral or intravenous antibiotics * No other second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix unless the malignancy was localized and treated or resected with \> 90% probability of cure PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Prior anti-CD20 therapy allowed provided patient achieved a partial or complete response * No concurrent steroids during rituximab administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Engraftment | Up to 43 days | Median days to neutrophil and platelet recovery. Neutrophil recovery is defined as absolute neutrophil count \>= 500 cells per microliter; platelet recovery is defined as untransfused platelet count \>= 20 \* 10\^9 cells per liter. |
| Non-relapse Mortality | 5 years | Number of participants who died for reasons related to protocol treatment. |
| Event-free Survival | 5 years | Percentage of participants alive without disease relapse. |
Countries
United States
Participant flow
Pre-assignment details
16 participants were screen failures. IRB allowed 3 of those participants to be analyzed along with the 78 who were treated as part of the study. Because the 3 additional participants received the exact same protocol intervention, the total population for analysis purposes is 81.
Participants by arm
| Arm | Count |
|---|---|
| R-HiCy Rituximab (R) and high-dose cyclophosphamide (HiCy) with pegfilgrastim support.
Pegfilgrastim: 6 mg SQ 24-48 hours after last dose of cyclophosphamide.
Rituximab: 375 mg/m\^2/day on Days 1, 4, 8, 11, 45, and 52.
Cyclophosphamide: 50 mg/kg/day on Days 15, 16, 17, and 18. | 81 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 11 |
Baseline characteristics
| Characteristic | R-HiCy | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 10 Participants | — |
| Age, Categorical Between 18 and 65 years | 71 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex/Gender, Customized Female | 17 Participants | — |
| Sex/Gender, Customized Male | 59 Participants | — |
| Sex/Gender, Customized Unknown | 5 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 81 |
| other Total, other adverse events | 64 / 81 |
| serious Total, serious adverse events | 15 / 81 |
Outcome results
Primary
Engraftment
Median days to neutrophil and platelet recovery. Neutrophil recovery is defined as absolute neutrophil count \>= 500 cells per microliter; platelet recovery is defined as untransfused platelet count \>= 20 \* 10\^9 cells per liter.
Time frame: Up to 43 days
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| R-HiCy | Engraftment | Neutrophil | 15 days |
| R-HiCy | Engraftment | Platelet | 15 days |
Primary
Event-free Survival
Percentage of participants alive without disease relapse.
Time frame: 5 years
Population: Participants were split into two populations for this outcome only: mantle-cell lymphoma and other low-grade B-cell tumors.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| R-HiCy | Event-free Survival | Mantle-cell lymphoma | 39 percentage of participants |
| R-HiCy | Event-free Survival | Other low-grade B-cell tumors | 40 percentage of participants |
Primary
Non-relapse Mortality
Number of participants who died for reasons related to protocol treatment.
Time frame: 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| R-HiCy | Non-relapse Mortality | 0 Participants |