R-ICE and High-Dose Cyclophosphamide With PET/CT for Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Study Overview
=================
Brief Summary
-----------------
This research is being done to see if a PET scan that is obtained after 3 cycles of a standard chemotherapy regimen can help guide treatment for patients with a blood disease called Non-Hodgkin's Lymphoma. The standard treatment for newly diagnosed lymphoma is 6 to 8 cycles of chemotherapy like the CHOP combination (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone). This regimen can cure about half of patients with lymphoma, but in many others disease relapses (comes back). Relapses are generally treated with more chemotherapy. We believe that a PET scan (a type of imaging study that lights up in areas of cells with high activity such as lymphoma), may identify patients early who are at high risk of relapse. The purpose of this research study is to find out if people whose treatment is changed early to an intensification regimen (high dose chemotherapy) based on a positive PET scan will have longer remissions than they would if they did not receive that high dose chemotherapy.

Detailed Description
-----------------
Patients will receive 3 cycles of chemotherapy prior to mid-treatment PET-CT. Rituximab-CHOP, or an equivalent regimen must be used. During the third cycle of Rituximab-CHOP chemotherapy, a PET-CT scan will be performed. The PET scan will be designated as negative or positive. Based on the results, patients will either complete standard dose therapy or receive two cycles of R-ICE followed by high dose cyclophosphamide and rituximab. A repeat PET-CT is required between 4 to 6 weeks following treatment completion. Patients will be followed-up every 4 months for 2 years, then every 6 months for one year, then annually until 5 years.

Official Title
-----------------
Treatment Intensification With R-ICE and High-Dose Cyclophosphamide for Diffuse Large B-Cell Non-Hodgkin's Lymphoma Based on Early [18F] FDG-PET Scanning

Conditions
-----------------
Non-Hodgkin's Lymphoma

Intervention / Treatment
-----------------
* Biological: Rituximab
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Prednisone
* Drug: Ifosfamide
* Drug: Carboplatin
* Drug: Etoposide
* Drug: High-dose cyclophosphamide
* Procedure: PET scan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: One of the following Biopsy-confirmed, aggressive non-Hodgkin's lymphoma Diffuse large B-cell lymphoma Mediastinal (thymic) B-cell lymphoma Any stage (I through IV) as defined by the Ann Arbor staging system ECOG performance status of 0 to 2 Radiographically measurable disease No more than 3 cycles of chemotherapy for lymphoma Greater than or equal to 18 years Adequate pulmonary, cardiac, hepatic, or renal function HIV antibody negative Women- Not pregnant or breastfeeding Men of reproductive potential must agree to use contraception Exclusion Criteria: Patients with the following aggressive lymphomas are not eligible: Mantle cell Lymphoblastic Burkitt's Mycosis fungoides/Sezary's syndrome HTLV-1 associated T-cell leukemia/lymphoma Primary CNS lymphoma HIV-associated lymphoma Transformed lymphomas Immunodeficiency-associated lymphomas Previous diagnosis of another hematologic malignancies Progressive disease on CHOP or Rituximab-CHOP Active CNS involvement by lymphoma Serious co-morbid disease that could preclude full participation in study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PET Negative<br>R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or an equivalent anthracycline-containing regimen for 3 cycles, followed by PET scan. Participants with a negative PET scan will complete their chemotherapy regimen as prescribed by their oncologist. | Biological: Rituximab<br>* 375 mg/m^2 on Day 1 of each cycle as part of R-CHOP or R-ICE. Also given 375 mg/m^2 on Days 1, 30, and 37 as part of HiCy.<br>* Other names: Rituxan;Drug: Cyclophosphamide<br>* 750 mg/m^2 on Day 1 of each cycle as part of R-CHOP.<br>* Other names: Cytoxan;Drug: Doxorubicin<br>* 50 mg/m^2 on Day 1 of each cycle as part of R-CHOP.<br>* Other names: Hydroxydaunorubicin;Drug: Vincristine<br>* 1.4 mg/m^2 on Day 1 of each cycle as part of R-CHOP.<br>* Other names: Oncovin;Drug: Prednisone<br>* 100 mg/day on Days 1-5 of each cycle as part of R-CHOP.<br>Procedure: PET scan<br>* Performed once between Days 16-20 of cycle 3 of R-CHOP.<br>* Other names: FDG-PET;|
| Active Comparator: PET Positive<br>R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or an equivalent anthracycline-containing regimen for 3 cycles, followed by PET scan. Participants with a positive PET scan will receive two cycles of R-ICE (rituximab, ifosfamide, carboplatin, etoposide) followed by HiCy (high-dose cyclophosphamide). | Biological: Rituximab<br>* 375 mg/m^2 on Day 1 of each cycle as part of R-CHOP or R-ICE. Also given 375 mg/m^2 on Days 1, 30, and 37 as part of HiCy.<br>* Other names: Rituxan;Drug: Cyclophosphamide<br>* 750 mg/m^2 on Day 1 of each cycle as part of R-CHOP.<br>* Other names: Cytoxan;Drug: Doxorubicin<br>* 50 mg/m^2 on Day 1 of each cycle as part of R-CHOP.<br>* Other names: Hydroxydaunorubicin;Drug: Vincristine<br>* 1.4 mg/m^2 on Day 1 of each cycle as part of R-CHOP.<br>* Other names: Oncovin;Drug: Prednisone<br>* 100 mg/day on Days 1-5 of each cycle as part of R-CHOP.<br>Drug: Ifosfamide<br>* 2000 mg/m^2/day on Days 1-3 of each cycle as part of R-CHOP.<br>* Other names: Ifex;Drug: Carboplatin<br>* Given on Day 2 of each cycle as part of R-CHOP. Dosed according to renal function.<br>* Other names: Paraplatin;Drug: Etoposide<br>* 100 mg/m^2/day on Days 1-3 of each cycle as part of R-CHOP.<br>* Other names: VP-16;Drug: High-dose cyclophosphamide<br>* 50 mg/kg/day on Days 2-5 of HiCy.<br>* Other names: HiCy;Procedure: PET scan<br>* Performed once between Days 16-20 of cycle 3 of R-CHOP.<br>* Other names: FDG-PET;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free Survival in Patient Receiving Early Treatment Intensification Based on a Positive Mid-treatment PET Scan |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival in Patients Whose Treatment is Determined on the Basis of a Mid-treatment [18F] FDG-PET Scan Result. |  | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
B-Cell, non-Hodgkin's, Lymphoma