Rituximab and Combination Chemotherapy in Treating Older Patients With Previously Untreated Diffuse Large B-Cell Lymphoma - Full Text View

Sponsored by:	German High-Grade Non-Hodgkin's Lymphoma Study Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00290667

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 diffuse large B-cell lymphoma.

Condition	Intervention	Phase
Lymphoma	Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: filgrastim Drug: prednisone Drug: rituximab Drug: vincristine sulfate Procedure: pharmacological study Procedure: radiation therapy	Phase II

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Filgrastim Prednisone Vincristine sulfate Vincristine Rituximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	2-Weekly CHOP With Dose-Dense Rituximab for the Treatment in Patients Aged 61 to 80 Years With Aggressive Diffuse Large B-Cell Lymphomas: A Phase-II / Pharmacokinetic Study (CHOP-R-ESC)

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, and protocol adherence 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 ]

Estimated Enrollment:	375
Study Start Date:	February 2004
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine a pharmacokinetic profile for rituximab within a CHOP-14 regimen comprising cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in elderly patients with previously untreated aggressive diffuse large B-cell lymphoma.
Evaluate the safety and toxicity profile of this regimen in these patients.

Secondary

Determine the rate of complete remission and event-free and overall survival in patients treated with this regimen.
Determine the rate of primary progression in patients treated with this regimen.

OUTLINE: This is an open-label, multicenter, pilot study.

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 filgrastim (G-CSF) subcutaneously on days 4-13. Treatment with CHOP chemotherapy repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients receive rituximab IV over 4 hours on days -4, -1, 10, 29, 57, 99, 155, and 239. 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.

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

After completion of study treatment, patients are followed for at least 1 year.

PROJECTED ACCRUAL: A total of 375 patients will be accrued for this study.

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 diffuse large 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 CNS lymphoma
No gastrointestinal 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 126 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

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000454505, DSHNHL-2004-1, EU-20536, DSHNHL-CHOP-R-ESC
Study First Received:	February 9, 2006
Last Updated:	January 14, 2009
ClinicalTrials.gov Identifier:	NCT00290667
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

Study placed in the following topic categories:

Prednisone
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Vincristine
Cyclophosphamide
Doxorubicin
Lymphoma, B-Cell

Lymphoma, large-cell
Lymphatic Diseases
B-cell lymphomas
Aggression
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antimitotic Agents
Antibiotics, Antineoplastic

Hormones
Glucocorticoids
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009