Monoclonal Antibody Therapy and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

Alliance for Clinical Trials in Oncology

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Treatments

Drug: vincristine sulfate

Drug: prednisone

Drug: doxorubicin hydrochloride

Biological: rituximab

Biological: epratuzumab

Drug: cyclophosphamide

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00301821

CDR0000459932 (Registry Identifier)

NCCTG-N0489

NCI-2012-02685 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.>

Enrollment

107 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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)