Lymphoma
Conditions
Keywords
contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma
Brief summary
RATIONALE: Monoclonal antibodies, such as epratuzumab and 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, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibody therapy together with chemotherapy may kill more cancer cells.\> PURPOSE: This phase II trial is studying how well giving monoclonal antibody therapy together with combination chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large B-cell lymphoma.
Detailed description
OBJECTIVES:\> Primary\> * Assess the efficacy of epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (CHOP), as measured by 12-month, event-free survival, in patients with previously untreated stage II, III, or IV diffuse large B-cell lymphoma.\> * Assess the use of positron emission tomography (PET) scan routinely early in treatment and after completion of treatment.\> * Assess the functional response rate (complete response, partial response, or stable disease by CT scan and PET negative) in patients treated with this regimen.\> * Assess the safety of this treatment regimen.\> Secondary\> * Correlate laboratory prognostic factors for large cell lymphoma with clinical response to this regimen.\> OUTLINE: This is a multicenter study.\> Patients receive epratuzumab IV over 1 hour on day 1, rituximab IV over 4-8 hours on day 1 or days 1 and 2, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 or 2, and oral prednisone on days 1-5 or 2-6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.\> After completion of study treatment, patients are followed periodically for up to 5 years.\> PROJECTED ACCRUAL: A total of 86 patients will be accrued for this study.\>
Interventions
BIOLOGICALepratuzumab
BIOLOGICALrituximab
DRUGcyclophosphamide
DRUGdoxorubicin hydrochloride
DRUGprednisone
DRUGvincristine sulfate
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed diffuse large B-cell lymphoma * B-cell phenotype (CD20+) as determined by immunohistochemistry (IHC) or flow cytometry * Stage II, III, or IV disease * CD22+ tumor by IHC\* NOTE: \*CD22 status may be determined after study enrollment * Measurable disease, defined as at least 1 lesion ≥ 1.5 cm by CT scan or physical exam * No relapsed or refractory non-Hodgkin's lymphoma * No history of transformed lymphoma * No CNS lymphoma * CNS symptoms or bone marrow or sinus involvement must have absence of CNS lymphoma confirmed by lumbar puncture PATIENT CHARACTERISTICS: * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-3 \- For patients with ECOG PS 3, the PS must be disease related * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Total bilirubin ≤ 2 mg/dL (if total bilirubin \> 2 mg/dL, direct bilirubin should be within normal limits) * AST ≤ 3 times upper limit of normal (ULN) (5 times ULN if there is liver involvement) * Creatinine ≤ 2 times ULN * Life expectancy ≥ 12 weeks * Negative pregnancy test * Not pregnant or nursing * Fertile patients must use effective contraception during and for 12 months after completion of study treatment * No active serious infection requiring antibiotics * No New York Heart Association class III or IV heart disease * No other primary malignancy within the past 5 years, except for squamous cell or basal cell carcinoma of the skin, in situ carcinoma of the cervix, or previously treated prostate cancer with a stable prostate-specific antigen * No known HIV positivity * No known hepatitis B or C infection * Ejection fraction ≥ 45% by MUGA or echocardiogram (required if patients has a history of heart disease or is ≥ 50 years old) * Willing to provide blood and tissue samples for mandatory translational research component of study PRIOR CONCURRENT THERAPY: * No prior therapy for diffuse large B-cell lymphoma, including the following: * Chemotherapy * Immunotherapy * Biologic therapy * Radiotherapy * Prior short course (≤ 14 days) of corticosteroids allowed * Prior splenectomy allowed * No prior pelvic irradiation * No other concurrent investigational agents * No concurrent chemotherapy, immunotherapy, or radiotherapy * No concurrent enrollment on another treatment study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival After 12 Months | From Baseline to 12 months | The primary endpoint of the trial was the percentage of the eligible patients who were alive and event-free 12 months after enrollment to the study (EFS12). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | time from study entry to 36 months | Percentage of participants alive at different time points |
| Progression-free Survival (PFS) | the time from study entry to 36 months | Percentage of participants Progression-free at different time points. Response was assessed using International Workshop Response Criteria.38 Response is based on CT alone. Relapse or progression is defined as Enlarging liver/spleen, new sites, New or increased lymph nodes, New or Increased lymph node masses, bone marrow reappearance. |
| Overall Response Rate (ORR) | Baseline to first 6 cycles of treatment | Overall response rate will be estimated by the number of patients with objective status of partial response (PR), unconfirmed complete response (CRu), or complete response (CR) during the first 6 cycles of treatment divided by number of evaluable patients (met eligibility criteria, signed consent form, and started treatment). Response was assessed using International Workshop Response Criteria.38 Response is based on CT alone. Relapse or progression is defined as Enlarging liver/spleen, new sites, New or increased lymph nodes, New or Increased lymph node masses, bone marrow reappearance. |
Countries
United States
Participant flow
Recruitment details
For this study 107 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) were enrolled. Twenty-six (24%) patients were declared ineligible based on pathology review; 1 patient canceled before beginning treatment.
Participants by arm
| Arm | Count |
|---|---|
| Epratuzumab + Rituximab + CHOP One arm, open label. Epratuzumab, Rituximab, Cyclophosphamide, Doxorubicin hydrochloride, Prednisone, Vincristine sulfate. | 107 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Cancel | 1 |
| Overall Study | Ineligible | 25 |
Baseline characteristics
| Characteristic | Epratuzumab + Rituximab + CHOP |
|---|---|
| Age, Continuous | 62 years |
| Region of Enrollment United States | 107 participants |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 105 / 106 |
| serious Total, serious adverse events | 72 / 106 |
Outcome results
Primary
Event-free Survival After 12 Months
The primary endpoint of the trial was the percentage of the eligible patients who were alive and event-free 12 months after enrollment to the study (EFS12).
Time frame: From Baseline to 12 months
Population: First 76 eligible participants were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epratuzumab + Rituximab + CHOP | Event-free Survival After 12 Months | 78 percentage of participants |
Secondary
Overall Response Rate (ORR)
Overall response rate will be estimated by the number of patients with objective status of partial response (PR), unconfirmed complete response (CRu), or complete response (CR) during the first 6 cycles of treatment divided by number of evaluable patients (met eligibility criteria, signed consent form, and started treatment). Response was assessed using International Workshop Response Criteria.38 Response is based on CT alone. Relapse or progression is defined as Enlarging liver/spleen, new sites, New or increased lymph nodes, New or Increased lymph node masses, bone marrow reappearance.
Time frame: Baseline to first 6 cycles of treatment
Population: Out of the 107 patients enrolled, Twenty-five patients were declared ineligible based on pathology review; 1 patient canceled before beginning treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epratuzumab + Rituximab + CHOP | Overall Response Rate (ORR) | 95 percentage of participants |
Secondary
Overall Survival
Percentage of participants alive at different time points
Time frame: time from study entry to 36 months
Population: Intent To Treat (All Patients)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Epratuzumab + Rituximab + CHOP | Overall Survival | Overall Survival at 12 months | 89 percentage of Participants |
| Epratuzumab + Rituximab + CHOP | Overall Survival | Overall Survival at 24 months | 81 percentage of Participants |
| Epratuzumab + Rituximab + CHOP | Overall Survival | Overall Survival at 36 months | 80 percentage of Participants |
Secondary
Progression-free Survival (PFS)
Percentage of participants Progression-free at different time points. Response was assessed using International Workshop Response Criteria.38 Response is based on CT alone. Relapse or progression is defined as Enlarging liver/spleen, new sites, New or increased lymph nodes, New or Increased lymph node masses, bone marrow reappearance.
Time frame: the time from study entry to 36 months
Population: Intent To Treat (All Patients)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Epratuzumab + Rituximab + CHOP | Progression-free Survival (PFS) | Progression Free Survival at 12 months | 85 percentage of participants |
| Epratuzumab + Rituximab + CHOP | Progression-free Survival (PFS) | Progression Free Survival at 24 months | 77 percentage of participants |
| Epratuzumab + Rituximab + CHOP | Progression-free Survival (PFS) | Progression Free Survival at 36 months | 76 percentage of participants |