Rituximab and Combination Chemotherapy in Treating Older Patients With Diffuse Large B-Cell Lymphoma

M.D. Anderson Cancer Center

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Drug: Cyclophosphamide; Drug: Prednisone; Biological: Rituximab; Biological: Filgrastim; Biological: Pegfilgrastim; Drug: Pegylated liposomal doxorubicin hydrochloride; Drug: Vincristine Sulfate

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00101010

MDA-CCOP-2004-0305

CDR0000407533

NCI-6485

2U10CA045809 (U.S. NIH Grant/Contract)

NCI-2009-00064 (Registry Identifier)

2004-0305 (Other Identifier)

Details and patient eligibility

About

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 work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating older patients with diffuse large B-cell lymphoma.

Full description

OBJECTIVES:

Primary

• Determine the clinical response rate in older patients with previously untreated aggressive diffuse large B-cell stage II-IV lymphoma treated with rituximab, cyclophosphamide, pegylated doxorubicin hydrochloride liposome (HCl), vincristine, and prednisone.
• Determine the cardiotoxicity and myelosuppression of this regimen in these patients.

Secondary

• Determine disease-free survival and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive rituximab intravenous (IV), cyclophosphamide IV over 1-1½ hours, pegylated doxorubicin HCl liposome IV over 1 hour, and vincristine IV on day 1, and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 6 and continuing until blood counts recover OR pegfilgrastim SC once on day 6 (24 hours after the completion of chemotherapy). Treatment repeats every 21 days for up to 8 courses in the absence of unacceptable toxicity, disease progression, active hepatitis B virus infection, or hepatitis. Patients with no response OR who achieve less than a partial response after 4 courses are removed from the study.

Patients are followed at 1 month, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A maximum of 80 patients will be accrued for this study within 27 months.

Enrollment: 80 patients

Sex: All

Ages: 61+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large B-cell lymphoma

  • Stage II, III, or IV disease
  • Previously untreated disease

• Measurable or evaluable disease

• No primary central nervous system (CNS) lymphoma or follicular B-cell lymphoma

PATIENT CHARACTERISTICS:

Age

• 61 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3*
• Platelet count > 100,000/mm^3* NOTE: * Unless due to lymphoma-related hypersplenism or bone marrow infiltration

Hepatic

• Bilirubin < 2 mg/dL
• Hepatitis B surface antigen negative
• Hepatitis B core antibody negative
• Hepatitis C Virus antibody negative

Renal

• Creatinine < 2 mg/dL

Cardiovascular

• left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or ple gated acquisition (MUGA) scan

• No uncontrolled hypertension or cardiac symptoms

• Cardiologist consultation required for patients with stage A cardiac failure or any of the following known heart diseases:

  • Diastolic dysfunction
  • Prior coronary artery bypass graft
  • Prior percutaneous transluminal coronary angioplasty
  • Prior stent insertion
  • Prior radiotherapy to the chest

• No myocardial infarction within the past 6 months

• No New York Heart Association class II-IV heart failure

• No uncontrolled angina

• No severe uncontrolled ventricular arrhythmias

• No clinically significant pericardial disease

• No acute ischemic or active conduction system abnormality by electrocardiogram (EKG)

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No psychiatric illness that would preclude study compliance or giving informed consent
• No other major life-threatening illness that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• See Cardiovascular

Surgery

• See Cardiovascular

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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80 participants in 1 patient group

Rituximab - Combination Chemotherapy

Experimental group

Description:

Rituximab 375 mg/m\^2 intravenous (IV), Cyclophosphamide IV over 1-1½ hours, Pegylated doxorubicin HCl liposome 40 mg/m\^2 IV over 1 hour, Vincristine 2 mg IV, day 1, \& oral Prednisone 40 mg/m\^2 days 1 - 5; Filgrastim (G-CSF) 5 mcg/kg subcutaneously (SC) once daily beginning day 6 continuing until blood counts recover OR Pegfilgrastim 6 mg SC once on day 6 (24 hours after chemotherapy). Treatment repeats every 21 days for up to 8 courses.

Treatment:

Biological: Pegfilgrastim

Drug: Pegylated liposomal doxorubicin hydrochloride

Drug: Cyclophosphamide

Biological: Filgrastim

Drug: Vincristine Sulfate

Drug: Prednisone

Biological: Rituximab