Rituximab and Combination Chemotherapy in Treating Older Patients With Previously Untreated B-Cell Lymphoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00290667
First received: February 9, 2006
Last updated: September 9, 2011
Last verified: March 2010
  Purpose

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. 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 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 previously untreated B-cell lymphoma.


Condition Intervention Phase
Lymphoma
Biological: pegfilgrastim
Biological: rituximab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Other: pharmacological study
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: 2-Weekly CHOP Chemotherapy With Dose-Dense Rituximab for the Treatment of Patients Aged 61 to 80 Years With Aggressive CD-20 Positive B-Cell Lymphomas: A Phase-II/Pharmacokinetic Study (CHOP-R-ESC)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Pharmacokinetics (in first 20 patients of each cohort with a distinct variation of the rituximab schedule) assessed on days -4, -1, 10, 29, 57, 99, 155, 239, 267, 295, 407, and 491 of treatment [ Designated as safety issue: No ]
  • Safety and treatment related deaths at 3 months after study completion [ Designated as safety issue: Yes ]
  • Toxicity assessed by NCI criteria, adverse events, serious adverse events, protocol adherence, and treatment-related deaths at 3 months after study completion [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to treatment failure assessed at 2 years within the study and periodically thereafter [ Designated as safety issue: No ]
  • Complete response rate assessed at 2 years within the study and periodically thereafter [ Designated as safety issue: No ]
  • Progression rate [ Designated as safety issue: No ]
  • Survival time [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 332
Study Start Date: February 2004
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine a pharmacokinetic profile for pharmacokinetics-based or rituximab within a CHOP-14 regimen comprising cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in elderly patients with previously untreated aggressive B-cell lymphoma.
  • To determine whether increased single-doses of rituximab for males can compensate their lower serum levels.
  • Evaluate the safety and toxicity profile of this regimen in male patients.

Secondary

  • Determine the rate of complete responses, primary progressions under therapy, event-free survival, progression-free survival, and overall survival in patients treated with this regimen.
  • Determine the rate of primary progression in patients treated with this regimen.

OUTLINE: This is a multicenter study. All patients undergo the following treatment.

  • Prephase treatment: Patients receive vincristine subcutaneously on day -6 and oral prednisone on days -6 to 0.
  • Immunochemotherapy and radiotherapy: Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Patients also receive pegfilgrastim subcutaneously on days 4, 18, 32, 46, 60, and 74. Treatment with CHOP chemotherapy repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who show no response after course 4 of CHOP chemotherapy proceed to salvage chemotherapy off study.

Patients are evaluated 2-4 weeks after completion of CHOP. Patients with initial bulky disease (i.e., diameter ≥ 7.5 cm) or extranodal involvement AND achieving complete remission (CR), unconfirmed CR (CRu), or partial remission undergo radiotherapy 5 days a week for 4 weeks. Patients who do not achieve CR or CRu 2 months after completion of radiotherapy proceed to salvage chemotherapy off study.

Patients are then stratified according to center, International Prognostic Index (1-2 vs 3-5), disease involvement (bulky vs extranodal vs bulky and/or extranodal), age (61-70 years old vs 71-80 years old), and gender. Patients are randomized to 1 of 2 treatment arms.

  • Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m^2 (females) and 500 mg/m^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.
  • Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m^2 (females) and 500 mg/m^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.

Some patients undergo blood sample collection periodically during and after treatment for pharmacokinetic studies.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year therafter.

  Eligibility

Ages Eligible for Study:   61 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histological diagnosis of aggressive B-cell lymphoma

    • Previously untreated disease
    • Stage I-IV disease
  • CD20-positive disease
  • Any International Prognostic Index (IPI) score
  • No secondary lymphoma after prior chemotherapy or radiotherapy
  • No primary CNS lymphoma
  • No primary gastrointestinal (MALT) lymphoma

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 3 months
  • AST and ALT ≤ 3 times normal unless related to lymphoma
  • Bilirubin ≤ 2 mg/dL unless related to lymphoma
  • Creatinine ≤ 2 times normal unless related to lymphoma
  • Fertile patients must use effective contraception
  • No known allergic reactions against foreign proteins
  • No active infections requiring systemically administered antibiotics or antiviral medications
  • No noncompensated heart failure
  • No dilatative cardiomyopathy
  • No coronary heart disease with ST-segment depression in ECG
  • No myocardial infarction during the past 6 months
  • No chronic lung disease with hypoxemia
  • No severe noncompensated hypertension
  • No severe noncompensated diabetes mellitus
  • No clinical signs of cerebral dysfunction
  • No severe psychiatric disease
  • No known HIV infection
  • No active chronic hepatitis B or C infection
  • No other concurrent diseases that exclude the administration of therapy as outlined by the study protocol

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 12 weeks since prior clinical trial participation
  • No prior participation in this study
  • No prior therapy, including murine antibody, for this cancer
  • No prior organ transplantation
  • No concurrent response-adapted radiotherapy ("iceberg radiotherapy")
  • No other concurrent anticancer chemotherapy or other study medication
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00290667

  Show 338 Study Locations
Sponsors and Collaborators
German High-Grade Non-Hodgkin's Lymphoma Study Group
Investigators
Study Chair: Michael G.M. Pfreundschuh, MD Universitaetsklinikum des Saarlandes
Investigator: Norbert Schmitz, MD, PhD Asklepios Klinik St. Georg
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00290667     History of Changes
Other Study ID Numbers: CDR0000454505, DSHNHL-2004-1, EU-20536, DSHNHL-CHOP-R-ESC, EUDRACT-2005-00529-68
Study First Received: February 9, 2006
Last Updated: September 9, 2011
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage I adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult Burkitt lymphoma
stage I adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse mixed cell lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
stage I adult diffuse small cleaved cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large-Cell, Immunoblastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Doxorubicin
Prednisone
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on April 16, 2014