Clinical trial NCT00324467: Tailoring Treatment for B Cell Non-hodgkin's Lymphoma Based on PET Scan Results Mid Treatment
Official title: Phase II Trial Investigating Tailoring First-Line Therapy For Advanced Stage Diffuse Large B-Cell Non-Hodgkin's Lymphoma Based on Mid-Treatment Positron Emission Tomography (PET) Scan Results
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lymphoma, Non-Hodgkin
Advanced Stage Diffuse Large B-Cell Non-Hodgkin's Lymphoma
Keywords: NON-HODGKIN'S LYMPHOMA
POSITRON EMISSION TOMOGRAPHY
PET
DLBCL
R-CHOP
R-ICE
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2006-05-11
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess whether patients who are likely to fail R-CHOP, as predicted by a mid-treatment PET scan, can have an improved outcome if switched to a standard salvage regimen R-ICE (rituximab, ifosfamide, carboplatin, etoposide).

Patients who have a negative PET scan after 4 cycles of R-CHOP have an excellent prognosis (\>85% chance of cure) and should complete treatment with 6 cycles of standard R-CHOP. Patients who have a positive PET scan after 4 cycles of R-CHOP have a very poor prognosis (\~10% chance of cure) and may have an improved outcome if switched to a non-cross resistant chemotherapy combination R-ICE.

Detailed description: This is a phase II trial investigating tailoring first-line therapy for advanced stage diffuse large B-cell NHL (DLBCL) based on a mid-treatment 18F-FDG- positron-emission tomography (PET) scan result. More than half of all patients with DLBCL can be cured with 6-8 cycles of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Patients who are not cured with R-CHOP have a very poor prognosis. This study will assess whether patients who are likely to fail R-CHOP, as predicted by a mid-treatment PET scan, can have an improved outcome if switched to a standard salvage regimen R-ICE (rituximab, ifosfamide, carboplatin, etoposide).

Objectives:

* To assess the efficacy of tailoring first-line therapy based on a mid- treatment PET scan result for patients with advanced stage DLBCL.
* To assess the progression-free survival (PFS) in patients with advanced stage DLBCL who have a negative mid-treatment PET scan and receive standard therapy with six cycles of CHOP-R and patients with a positive mid-treatment PET scan who receive four cycles of CHOP-R followed by four cycles of R-ICE chemotherapy.
* To assess the overall survival (OS) in patients with advanced stage DLBCL who have a negative mid-treatment PET scan and receive standard therapy with six cycles of CHOP-R and patients with a positive mid-treatment PET scan who receive four cycles of CHOP-R followed by four cycles of R-ICE chemotherapy.

Eligibility criteria: Inclusion Criteria:

* 18 years of age or older
* newly diagnosed histologically proven CD-20 positive diffuse large B- cell lymphoma by tissue biopsy, listed under peripheral B-cell neoplasm according to the WHO/REAL classification (diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, T-cell rich B-cell lymphoma, intravascular large B-cell lymphoma)
* Advanced stage disease defined as - patients with stage III or stage IV disease; or patients with stage I or stage II disease with one of the following additional criteria: B-symptoms, or disease that is not radio- encompassable within a single involved field, or not a candidate for brief chemotherapy and irradiation, or the presence of bulky disease (any single mass =\> 10 cm)
* Previously untreated or treated with up to 3 cycles of standard dose 3- weekly R-CHOP chemotherapy prior to enrollment (i.e. patients may be enrolled prior to initiation of the fourth cycle of R-CHOP chemotherapy)
* ECOG Performance Status 0,1 or 2 at time of enrollment
* No evidence of progressive disease while on R-CHOP chemotherapy
* The patient must sign the consent form prior to registration

Exclusion Criteria:

* Patients with a history of any other lymphoproliferative disorder, including prior history of indolent NHL
* Patients with a history of prior or concurrent malignancies within 5 years of the current diagnosis, except adequately treated non- melanoma skin cancer, and curatively treated in-situ cancer of the cervix
* Known HIV infection
* Known hepatitis B virus infection
* Pregnancy or lactation. Men and women of childbearing age must be using adequate contraception.
* Significant renal insufficiency (serum creatinine \> 200 mmol/L), unless due to lymphoma
* Significant hepatic insufficiency (serum total bilirubin \> 30 mmol/L), unless due to lymphoma
* Cardiac contraindication to doxorubicin therapy (e.g. abnormal contractility on echocardiography). If history of cardiac disease, ejection fraction must be within normal limits for age.
* Neurologic contraindication to vincristine (e.g. peripheral neuropathy)
* Absolute neutrophil count \<1.5 x 109/L (unless due to bone marrow involvement with lymphoma or due to initiation of R-CHOP chemotherapy)
* Platelet count \< 100 x 109/L (unless due to splenomegaly, bone marrow involvement with lymphoma or due to initiation of R-CHOP chemotherapy)
* Evidence of active systemic infection
* Any medical condition that in the opinion of the investigator would compromise treatment delivery, add toxicity or impair assessment

Primary outcomes:
measure: Progression-free survival (PFS) in participants with advanced stage DLBCL
timeFrame: Estimated two years
Secondary outcomes:
measure: Overall survival (OS) in participants with advanced stage DLBCL
timeFrame: Several years
measure: The safety of R-ICE therapy in first-line therapy of DLBCL following four cycles of R-CHOP as assessed using the NCI Common Terminology Criteria for Adverse Events Version 3.0
timeFrame: Six months
measure: Investigate clinical and biologic markers that characterize participant heterogeneity and may serve as predictors of response to therapy and overall outcome.
timeFrame: 1 year
measure: Efficacy of tailoring first-line therapy bases on a mid-treatment PET scan result for patients with advanced stage DLBCL
timeFrame: Four to six months
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BC Cancer Agency
state: British Columbia
Study officials:
affiliation: BC Cancer Agency - Vancouver Centre
name: Laurie H Sehn, MD
role: PRINCIPAL_INVESTIGATOR
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