Clinical trial NCT00079261: Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone With or Without Gemcitabine in Treating Patients With Previously Untreated Aggressive Non-Hodgkin's Lymphoma
Official title: Gem-CHOP: A Randomized Phase II Study of Gemcitabine Combined With CHOP in Untreated Aggressive Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Small Intestine Cancer
Keywords: contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 3 follicular lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
adult grade III lymphomatoid granulomatosis
small intestine lymphoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2004-03-10
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, prednisone, and gemcitabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more cancer cells.

PURPOSE: This randomized phase II trial is studying giving combination chemotherapy together with gemcitabine to see how well it works compared to giving combination chemotherapy alone in treating patients with previously untreated aggressive stage II, stage III, or stage IV non-Hodgkin's lymphoma.

Detailed description: OBJECTIVES:

Primary

* Compare the complete response rate (confirmed or unconfirmed) in patients with previously untreated aggressive non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone with vs without gemcitabine.

Secondary

* Compare the safety profile of these regimens in these patients.
* Compare the feasibility of these regimens, defined as the proportion of courses given as scheduled, in these patients.
* Compare freedom from treatment failure in patients treated with these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to participating center, International Prognostic Index score (0-2 vs 3-5), and histology (B cell vs T cell). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral or IV prednisone on days 1-5.
* Arm II: Patients receive CHOP chemotherapy as in arm I and gemcitabine IV over 30 minutes on days 1 and 8.

In both arms, treatment repeats every 3 weeks for 3 courses in the absence of unacceptable toxicity or progressive disease. Patients achieving partial response or complete or unconfirmed complete response receive an additional 5 courses of therapy (for a total of 8 courses).

Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 76-82 patients (38-41 per treatment arm) will be accrued for this study within 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL) of 1 of the following WHO subtypes:

  * Diffuse large B large cell lymphoma (including all clinical and morphologic variants)
  * Grade 3 follicular lymphoma
  * Extranodal T/NK cell lymphoma, nasal type
  * Enteropathy-type T cell lymphoma
  * Hepato-splenic T cell lymphoma
  * Peripheral T cell lymphoma, unspecified
  * Angioimmunoblastic lymphoma
  * Anaplastic large cell lymphoma, systemic type
* Stage II-IV disease
* At least 1 site of measurable disease (e.g., lymph node or lymph node mass)
* The following subtypes are not allowed:

  * Mantle cell lymphoma
  * Burkitt's lymphoma
  * Precursor B or T cell lymphoma
  * Primary cutaneous B or T cell lymphoma
* No CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

Age

* 18 to 70

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* WBC \> 3,000/mm\^3
* Neutrophil count \> 1,000/mm\^3
* Platelet count \> 100,000/mm\^3

Hepatic

* Bilirubin \< 2.5 times normal (unless due to lymphoma)
* ALT and AST \< 2.5 times normal (unless due to lymphoma)

Renal

* Creatinine \< 2.0 mg/dL

Cardiovascular

* No severe cardiac disease that would preclude study participation or limit life expectancy

Pulmonary

* FEV_1 and DLCO ≥ 75% of predicted (unless due to lymphoma)
* No severe pulmonary disease that would preclude study participation or limit life expectancy

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* HIV negative
* No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
* No severe neurologic or metabolic disease that would preclude study participation or limit life expectancy
* No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent monoclonal antibodies

Chemotherapy

* No other concurrent chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* No prior radiotherapy
* No concurrent radiotherapy

Surgery

* Not specified

Other

* No prior cytotoxic agents
* No prior treatment for NHL
* No other concurrent anticancer therapy
* No other concurrent investigational drugs

Primary outcomes:
measure: Complete response as assessed by Cheson criteria
Secondary outcomes:
measure: Toxicity as assessed by CTC 2.0
measure: Proportion of courses given as scheduled
measure: Freedom from treatment failure as assessed by Cheson criteria
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Wilrijk
country: Belgium
facility: Algemeen Ziekenhuis Sint-Augustinus
city: Zagreb
country: Croatia
facility: University Hospital Rebro
city: Cairo
country: Egypt
facility: National Cancer Institute - Cairo
city: Bordeaux
country: France
facility: Institut Bergonie
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
Study officials:
affiliation: University Hospital Rebro
name: Igor Aurer, MD, PhD
role: STUDY_CHAIR
References:
citation: Aurer I, Eghbali H, Raemaekers J, Khaled HM, Fortpied C, Baila L, van der Maazen RW; EORTC Lymphoma Group. Gem-(R)CHOP versus (R)CHOP: a randomized phase II study of gemcitabine combined with (R)CHOP in untreated aggressive non-Hodgkin's lymphoma--EORTC lymphoma group protocol 20021 (EudraCT number 2004-004635-54). Eur J Haematol. 2011 Feb;86(2):111-6. doi: 10.1111/j.1600-0609.2010.01540.x. Epub 2010 Dec 22.