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Protocol Details

Phase III Randomized Study of R-CHOP v. Dose-Adjusted EPOCH-R with Molecular Profiling in Untreated de Novo Diffuse Large B-Cell Lymphomas

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

05-C-0252

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Children;
Fetuses;
Pregnant Women

Keywords

Microarray Histological Diagnosis;
Molecular Prognostic Model

Recruitment Keyword(s)

Diffuse Large B-Cell Lymphoma;
DLBCL

Condition(s)

Lymphoma, Large B-Cell;
Diffuse Large B-Cell Lymphoma

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: Rituximab
Drug: CHOP
Drug: EPOCH

Supporting Site

National Cancer Institute

This study will compare the effectiveness and side effects of two different treatments - R-CHOP and EPOCH-R - for aggressive B cell lymphoma.

Patients 18 years of age and older with stage II, III or IV diffuse or intravascular large B-cell lymphoma or any stage mediastinal (thymic) large B-cell lymphoma who have not previously been treated with chemotherapy may be eligible for this study.

Participants are randomly assigned for treatment in either: 1) group A, to receive R-CHOP, which includes the drugs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; or 2) group B, to receive dose-adjusted EPOCH-R, which includes etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab. Both groups receive the drugs intravenously (IV, through a needle in a vein) in the arm or through a central line (a tube surgically placed in the large vein under the collarbone or in the neck). Patients in group B may receive the drugs through a portable infusion pump. R-CHOP is a widely used standard treatment, and dose-adjusted EPOCH-R is a newer treatment developed over the last 14 years.

Patients in Group A (R-CHOP) are given rituximab by IV infusion on the first day of treatment over several hours. When these infusions are complete, cyclophosphamide, doxorubicin and vincristine are each given by IV infusion over about 1 hour. Prednisone is given by mouth every day for 5 days. Patients may also be given filgrastim-a drug to boost white cell production-by injection under the skin. This drug is started the day after R-CHOP treatment and is continued until white blood cell counts rise to acceptable levels (usually about 10 days). Patients at risk of their disease spreading to the central nervous system may be given methotrexate injected into the spinal fluid. Patients also will be given colace or other drugs to prevent constipation and a drug to guard against stomach ulcers. R-CHOP treatment is repeated every 21 days for a total of eight cycles. After the fourth, sixth and eighth, patients are evaluated with blood and imaging studies (computed tomography and/or magnetic resonance imaging scans). Those whose lymphoma does not respond to treatment are withdrawn from the study and returned to the care of their respective physicians.

Patients in Group B (EPOCH-R) receive rituximab as described above for Group A. Doxorubicin, etoposide and vincristine are then given by continuous infusion over the next 4 days for a total of 96 hours. Prednisone is given by mouth twice a day for 5 days. Cyclophosphamide is started by IV infusion on day 5. Filgrastim, to boost white cells, and drugs to prevent infections, stomach ulcers and constipation are given as described above for Group A. Dose-adjusted EPOCH-R is repeated in 21-day treatment cycles for either six or eight cycles, depending on the patient's response. After the fourth and sixth cycles, patients are evaluated with blood tests and imaging studies. Patients whose disease does not respond to treatment are withdrawn from the study and returned to the care of their respective physicians.

Research tests are done on blood, bone marrow, tumor tissue or other fluids to look at genes and proteins that might be involved in the development of B-cell lymphoma or the reaction of the immune system.

Patients whose cancer disappears with treatment return to the clinic for follow-up exams every 3 months for the first 2 years and then each 6 months for another 3 years. Those whose disease does not disappear or recurs are returned to the care of their physicians or offered treatment in another study, if an appropriate study is available.

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Eligibility

INCLUSION CRITERIA:

As of protocol update #14 the PET/ CT imaging companion study CALGB 580603 will be required of all participants enrolling onto the treatment study CALGB 50303. Participation on CALGB 580603 will no longer be optional in order to participate in CALGB 50303.

Histologically documented de novo CD20+ DLBCL with stage II, III or IV disease. Stage I primary mediastinal (thymic) DLBCL is also eligible. Patients with an underlying low-grade lymphoma, such as a transformed lymphoma or low grade lymphoma in the bone marrow are not eligible. Diagnosis should be based on an adequate tissue sample, including open biopsy or core needle biopsy. Needle aspiration for primary diagnosis is unacceptable. Patients must have one of the following WHO {21} classification subtypes:

Diffuse large B-cell lymphoma (includes morphological variants: centroblastic; immunoblastic; T-cell/histiocyte rich; and anaplastic).

Mediastinal (thymic) large B-cell lymphoma.

Intravascular large B-cell lymphoma.

Note: Failure to submit pathology block within 60 days of patient registration will be considered a major protocol violation.

Fresh (frozen) tumor biopsy must be available or attempted (see repeat tissue biopsy guidance below). A frozen tumor biopsy equivalent to a minimum of four at least 16 gauge needle cores is an important component of this study. Patients without adequate frozen material should have a biopsy performed to obtain material. If a biopsy is performed and does not yield adequate material, the patient is still eligible for the study. If a biopsy cannot be done safely, the patient may still be eligible for the study if permission is granted in writing (e-mail) by the study chairs (Drs. Wilson or Zelenetz) or their designees.

Drs. Wilson or Zelenetz may be consulted to discuss situations involving invasive biopsy procedures that may pose an increased risk to the patient.

NOTE: THIS STUDY DOES NOT ALLOW CONCURRENT RADIATION UNLESS A PATIENT HAS A DOCUMENTED CNS TREATMENT FAILURE WITH NO SYSTEMIC FAILURE. PLEASE DO NOT ENROLL A PATIENT YOU MIGHT WISH TO RADIATE.

No prior cytotoxic chemotherapy or rituximab. Patients may be entered if they have received prior limited field radiation therapy or a short course of glucocorticoids (less than 10 days ) for an urgent local disease complication at diagnosis (e.g., cord compression, SVC syndrome). Patients who have received chemotherapy for prior malignancies are not eligible.

Age greater than or equal to 18 years.

ECOG Performance Status 0-2.

No active ischemic heart disease or congestive heart failure. If there is suspicion of cardiac disease, a cardiac ejection fraction must show LVEF greater than 45%, but the study is not required.

No known lymphomatous involvement of the CNS. A lumbar puncture prior to study is not required in the absence of neurological symptoms.

No known HIV disease. Patients with a history of intravenous drug or any other behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus. The mechanism of disease in patients with HIV may be different from de novo diffuse large B cell lymphoma. Additionally, the immunocompromised state of patients with HIV infection may result in more extensive dose reductions than intended for the intensive therapeutic regimens used in this study. Therefore, patients who test positive or who are known to be infected are not eligible. An HIV test is not required for entry on protocol, but is required if the patient is perceived to be at risk.

Non pregnant and non-nursing. Treatment would expose an unborn child to significant risk. Women and men of reproductive potential should agree to use an effective form of contraception.

Patients with active medical processes (e.g., uncontrolled bacterial or viral infection, bleeding) not related to their lymphoma should be excluded.

Required Initial Laboratory Values:

ANC greater than or equal to 1000/ul

Platelets greater than or equal to 100,000/ul.

Creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than or equal to 50 cc/min.

Total Bilirubin less than or equal to 2 mg/dl.


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Citations:

Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6.

Martelli M, Gherlinzoni F, De Renzo A, Zinzani PL, De Vivo A, Cantonetti M, Falini B, Storti S, Meloni G, Rizzo M, Molinari AL, Lauria F, Moretti L, Lauta VM, Mazza P, Guardigni L, Pescarmona E, Pileri SA, Mandelli F, Tura S. Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin's lymphoma: an Italian multicenter randomized trial. J Clin Oncol. 2003 Apr 1;21(7):1255-62.

Kaiser U, Uebelacker I, Abel U, Birkmann J, Trumper L, Schmalenberg H, Karakas T, Metzner B, Hossfeld DK, Bischoff HG, Franke A, Reiser M, Muller P, Mantovani L, Grundeis M, Rothmann F, von Seydewitz CU, Mesters RM, Steinhauer EU, Krahl D, Schumacher K, Kneba M, Baudis M, Schmitz N, Pfab R, Koppler H, Parwaresch R, Pfreundschuh M, Havemann K. Randomized study to evaluate the use of high-dose therapy as part of primary treatment for "aggressive" lymphoma. J Clin Oncol. 2002 Nov 15;20(22):4413-9.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Wyndham H. Wilson, M.D.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 4-1479
10 Center Drive
Bethesda, Maryland 20892
(240) 760-6092
wilsonw@mail.nih.gov

Anna M. Juanitez, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 12C432C
10 Center Drive
Bethesda, Maryland 20892
(240) 858-3183
annamarie.juanitez@nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937
ncimo_referrals@mail.nih.gov

Clinical Trials Number:

NCT00118209

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