Molecular Risk Assessment in Planning Treatment for Patients With Non-Hodgkin's Lymphoma

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

RATIONALE: Analyzing genes that are present in cancer cells may be useful as a method for predicting the response of non-Hodgkin's lymphoma to cancer treatment. Imaging procedures such as positron emission tomography (PET) scans may improve the ability to measure how well cancer has responded to treatment.

PURPOSE: This phase II trial is studying molecular risk assessment to see how well it works in predicting response to therapy in patients who are receiving treatment for non-Hodgkin's lymphoma.

Condition or disease	Intervention/treatment	Phase
Lymphoma	Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate; Genetic: microarray analysis	Phase 2

Detailed Description:

OBJECTIVES:

• Determine whether molecular risk assessment can identify groups of patients with diffuse large B-cell non-Hodgkin's lymphoma (NHL) who will demonstrate at least 50% difference in early response rates to treatment as determined by positron-emission tomography (PET) imaging.
• Determine, by PET imaging, the response rate of patients treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab.
• Determine whether early response rates can be predicted by gene expression profiles at diagnosis in these patients.
• Compare gene expression profiles of patients with refractory or relapsed large cell NHL with profiles of the disease at diagnosis.
• Determine relapse-free and overall survival rates of these patients.
• Determine the feasibility of a new NHL treatment algorithm based on prognostic index and molecular risk, and early response assessment by PET imaging.

OUTLINE: Molecular risk assessment is performed using lymph node tissue from initial diagnosis to test for "activated" genes before starting treatment.

Patients receive rituximab IV over 3-6 hours, cyclophosphamide IV over 30 minutes, doxorubicin IV over 5 minutes, and vincristine IV over 5 minutes on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for 3-8 courses. Patients undergo whole-body positron-emission tomography (PET) scanning at baseline and after course 3 to determine response. Results from the genetic testing and PET scans are used to determine further treatment recommendations.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 36-50 patients will be accrued for this study.

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	9 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Molecular Risk Guided Treatment Of Diffuse Large B-Cell Non-Hodgkin's Lymphoma
Study Start Date :	October 2002
Actual Primary Completion Date :	April 2005
Actual Study Completion Date :	March 2006

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Intervention Details:

Biological: rituximab
Rituximab IV over 3-6 hours.Treatment repeats every 21 days for 3-8 courses.
Drug: cyclophosphamide
Cyclophosphamide IV over 30 minutes. Treatment repeats every 21 days for 3-8 courses.
Drug: doxorubicin hydrochloride
Doxorubicin IV over 5 minutes. Treatment repeats every 21 days for 3-8 courses.
Drug: prednisone
Oral prednisone on days 1-5. Treatment repeats every 21 days for 3-8 courses.
Drug: vincristine sulfate
Vincristine IV over 5 minutes on day 1. Treatment repeats every 21 days for 3-8 courses.
Genetic: microarray analysis
genetic testing

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Molecular risk assessment to see how well it works in predicting response to therapy in patients who are receiving treatment for non-Hodgkin's lymphoma. [ Time Frame: Results from the genetic testing and PET scans at baseline and after course 3 to determine response. ]

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large B-cell non-Hodgkin's lymphoma
• CD20 and/or CD19 positive by immunohistochemistry or flow cytometry
• Disease evaluable by positron-emission tomography scan
• Diagnostic tissue (either frozen or fresh unfixed) available for molecular testing or willing to undergo a repeat procedure to obtain such tissue
• No CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 3 mg/dL

Renal

• Creatinine no greater than 3 mg/dL

Cardiovascular

• LVEF at least 40%

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No significant organ dysfunction that would preclude study chemotherapy
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy
• No prior biological response modifier therapy

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy
• No prior radioimmunotherapy

Surgery

• Not specified

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Ohio
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-7284

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:	Omer N. Koc, MD	Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Omer N. Koc, MD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00055640 History of Changes
Other Study ID Numbers:	CWRU1402; P30CA043703 ( U.S. NIH Grant/Contract ); CWRU-060244; CWRU-1402
First Posted:	March 7, 2003
Last Update Posted:	June 10, 2010
Last Verified:	June 2010

Keywords provided by Case Comprehensive Cancer Center:

stage I adult diffuse large cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cyclophosphamide; Rituximab; Liposomal doxorubicin; Doxorubicin; Prednisone; Vincristine; Immunosuppressive Agents	Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Glucocorticoids; Hormones