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

This study has been terminated.
(slow accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00060346
First received: May 6, 2003
Last updated: February 11, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: cyclophosphamide
Drug: Doxorubicin
Drug: Prednisone
Drug: Vincristine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Pilot Study Of Rituximab Plus CHOP In Patients With Newly Diagnosed Waldenstrom's Macroglobulinemia

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Objective Response to Treatment [ Time Frame: Every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry ] [ Designated as safety issue: No ]
    Objective response assessed using standard myeloma response criteria. Objective response is defined as a > 50% reduction in the quantitative IgM or M-Spike levels from baseline levels. Response must be documented by two measurements separated by at least 3 weeks.


Enrollment: 16
Study Start Date: June 2004
Study Completion Date: August 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab + CHOP

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

Biological: rituximab
Rituximab is given intravenously. The initial rate is 50 mg/hr for the 1st hour. If no toxicity, the rate may be escalated in 50 mg/hr increments at 30-minute intervals to a maximum of 400 mg/hr. If the first dose is well tolerated, the initial rate for subsequent dose is 100 mg/hr, increased in 100 mg/hr increments at 30-minute intervals, not to exceed 400 mg/hr. If the patient experiences fever and rigors, the antibody infusion is discontinued. The severity of the side effects should be evaluated. If the symptoms improve, the infusion is continued initially at half the previous rate. Following the antibody infusion, the intravenous line should be maintained for medications as needed. If there are no complications after one hour of observation, the intravenous line may be discontinued.
Other Names:
  • IDEC-C2B8
  • Chimeric anti-CD20 monoclonal antibody
  • Rituxan
  • NSC# 687451
Drug: cyclophosphamide

Cyclophosphamide will be given at a dosage of 750 mg/m² intravenously on day 1 of each cycle (1 cycle =21 days) for 6 cycles. Dose is based on surface area calculated based on actual body weight.

The drug should be administered as a rapid IV infusion over 5 to 30 minutes.

Other Names:
  • Cytoxan
  • CTX
  • CPM
  • Neosar
Drug: Doxorubicin

Doxorubicin will be given intravenously at a dosage of 50 mg/m² on day 1 of each cycle for 6 cycles (1 cycle =21 days). Dose is based on surface area calculated based on actual body weight.

Doxorubicin should be administered as a continuous infusion into tubing of a freely flowing intravenous line for 5 -15 minutes. Avoid extravasation.

Other Names:
  • Adriamycin
  • Rubex
  • Adriamycin RDF
  • Adriamycin PFS
  • hydroxydaunorubicin
  • ADR
Drug: Prednisone
Prednisone will be administered at 100 mg/m² orally, days 1-5 of each cycle for 6 cycles (1 cycle =21 days). Dose is based on surface area calculated based on actual body weight.
Other Names:
  • Deltasone
  • Orasone
  • Medicortone
  • Panasol-S
  • Liqui-Pred
Drug: Vincristine

Vincristine will be administered 1.4 mg/m² intravenously (Maximum dose = 2.0 mg) on day 1 of each cycle for 6 cycles (1 cycle =21 days). Dose is based on surface area calculated based on actual body weight.

Given as IV push over 1 minute, using extravasation precautions.

Other Names:
  • Vinsacar PFS
  • vincristine sulfate
  • VCR
  • leucocristine
  • LCR

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00060346

  Show 153 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Rafat Abonour, MD Indiana University Melvin and Bren Simon Cancer Center
  More Information

Publications:
Abonour R, Zhang LA, Rajkumar V, et al.: Phase II pilot study of rituximab + CHOP in patients with newly diagnosed Waldenstroms macroglobulinemia, an Eastren Cooperative Oncology Group trial (study E1A02). [Abstract] Blood 110 (11): A-3616, 2007.

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00060346     History of Changes
Other Study ID Numbers: CDR0000301634, U10CA021115, E1A02
Study First Received: May 6, 2003
Results First Received: January 10, 2013
Last Updated: February 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eastern Cooperative Oncology Group:
Waldenstrom macroglobulinemia
Rituximab
CHOP

Additional relevant MeSH terms:
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Paraproteinemias
Vascular Diseases
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Prednisone
Rituximab
Vincristine
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 23, 2014