Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Waldenstrom's Macroglobulinemia

Eastern Cooperative Oncology Group

Status and phase: Terminated; Phase 2

Conditions: Lymphoma

Treatments: Drug: Doxorubicin; Drug: cyclophosphamide; Drug: Prednisone; Biological: rituximab; Drug: Vincristine

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00060346

E1A02 (Other Identifier)

CDR0000301634

U10CA021115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining rituximab 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 patients with newly diagnosed Waldenstrom's macroglobulinemia.

Full description

OBJECTIVES:

• Determine the response rate of patients with newly diagnosed Waldenstrom's macroglobulinemia treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
• Determine the associated toxic effects of this regimen, specifically the frequency of febrile neutropenia, in these patients.
• Determine the progression-free survival of patients treated with this regimen.
• Correlate baseline cytogenetic features and gene expression profiles with response in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

Patients receive rituximab intravenously (IV) over approximately 4 hours, cyclophosphamide IV over 5-30 minutes, doxorubicin IV over 5-15 minutes, and vincristine IV over 1 minute on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

ACTUAL ACCRUAL: A total of 16 patients were accrued for this study.

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of Waldenstrom's macroglobulinemia confirmed by the presence of the following:

  • Bone marrow lymphoplasmacytosis with: > 10% lymphoplasmacytic cells OR aggregates or sheets of one of the following: lymphocytes, plasma cells or lymphoplasmacytic cells on the bone marrow biopsy (measured within 4 weeks prior to registration)
  • Measurable disease defined as a quantitative immunoglobulin M (IgM) monoclonal protein of > 1,000 mg/dL obtained within 4 weeks prior to registration
  • Cluster of differentiation 20 (CD20) positive stain of bone marrow or lymph node samples obtained < 8 weeks prior to registration

• Impaired bone marrow function due to infiltration by lymphoplasmacytic lymphoma, defined by 1 of the following:

  • Hemoglobin no greater than 11 g/dL
  • Serum viscosity level relative to water of at least 4.0 centipoise

• Absolute neutrophil count at least 1,000/mm^3

• Platelet count at least 75,000/mm^3

• Bilirubin no greater than 3.0 mg/dL

• Aspartate aminotransferase (AST) no greater than 3 times upper limit of normal

• Creatinine no greater than 3.0 mg/dL

• Age of 18 and over

• ECOG (Eastern Cooperative Oncology Group) performance status 0-1

• Must be symptomatic with 1 of the following:

  • Clinically significant anemia (hemoglobin no greater than 11 g/dL)
  • Bulky lymphadenopathy
  • Symptoms attributable to hyperviscosity (e.g., nose bleeding, gingival bleeding, or retinal hemorrhage)

• History of heart disease allowed only if 1 of the following is demonstrated by echocardiography, multigated acquisition scan (MUGA), exercise MUGA, or coronary catheterization:

  • Ejection fraction of at least 45%
  • Normal fractional shortening of the left ventricle

• Must have been tested for hepatitis B surface antigen within 2 weeks of registration

• Negative pregnancy test

• Fertile patients must use effective contraception

Exclusion criteria

• Prior treatment for Waldenstrom's macroglobulinemia
• Prior anti-CD20 therapy
• Concurrent steroids exceeding 10 mg prednisone (or equivalent) per day
• Prior irradiation if less than 4 weeks had elapsed prior to registration and the date of last treatment
• Prior anthracyclines
• Prior malignancy except curatively treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other cancer curatively treated with surgery alone and from which patient has been disease free for at least 5 years
• Active heart disease
• Pregnant or nursing
• Myocardial infarction within the past 3 months
• Congestive heart failure
• Symptomatic ventricular arrhythmia

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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16 participants in 1 patient group

Rituximab + CHOP

Experimental group

Description:

Rituximab 375 mg/m2 day 1 of a 21-day cycle, followed by: Cyclophosphamide 750 mg/m2 Doxorubicin 50 mg/m2 Vincristine 1.4 mg/m2 and Prednisone 100 mg/m2 daily

Treatment:

Drug: Vincristine

Biological: rituximab

Drug: Prednisone

Drug: cyclophosphamide

Drug: Doxorubicin