Positron Emission Tomography Guided Therapy of Aggressive Non-Hodgkin's Lymphomas

Study Overview
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Brief Summary
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The main purpose of the PETAL trial is to determine whether patients with aggressive non-Hodgkin's lymphomas with a persistently positive PET scan after two cycles of chemotherapy benefit from a change of the treatment protocol.

Detailed Description
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Positron emission tomography performed after two cycles of (R-)CHOP chemotherapy (interim-PET) has been shown to predict long-term outcome in patients with aggressive non-Hodgkin's lymphomas. Patients with early normalization of pathological PET findings have an excellent prognosis, while patients with a persistently pathological PET scan have a high risk of non-response or relapse. Patients with a negative interim-PET scan (part A of the trial) will be randomized to receive either another four cycles of the (R-)CHOP regimen (arm A1) or four cycles of the (R-)CHOP regimen plus two additional doses of rituximab (arm A2). Randomisation in part A of the trial was stopped when the number of patients required was reached (128 patients in each treatment arm). Since then patients have been uniformly treated according to arm A2. Patients with a persistently positive interim-PET scan (part B of the trial) will be randomized to either continue treatment with another six (R-)CHOP cycles (arm B1) or switch to an alternative protocol used for the treatment of Burkitt's lymphoma (arm B2: six blocks according to the so-called B-ALL protocol of the German ALL study group). Patients refractory to or relapsing within two years after treatment according to parts A or B of the trial will receive age-adapted salvage protocols (patients < 60 years: high-dose chemotherapy with autologous stem cell transplantation; patients > 60 years: (R-)ESHAP protocol)(part C of the trial).

Official Title
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Positron Emission Tomography Guided Therapy of Aggressive Non-Hodgkin's Lymphomas

Conditions
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Lymphoma, High-grade

Intervention / Treatment
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* Drug: (R-)CHOP protocol
* Drug: B-ALL protocol
* Drug: (R-)CHOP protocol
* Drug: (R-)CHOP protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aggressive B-cell or T-cell non-Hodgkin's lymphoma Pathological pre-treatment PET scan Performance status ECOG 0-3 Age 18 - 80 years Ability to understand the purpose of the study and act accordingly Willingness to use adequate contraception Informed consent Exclusion Criteria: Burkitt's lymphoma Primary central nervous system lymphoma Previous chemo- and/or radiotherapy Other cancer within preceding 5 years HIV infection, active viral hepatitis or other uncontrolled infection Other medical conditions precluding administration of planned therapy Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: B1<br>Six cycles of the (R-)CHOP regimen. | Drug: (R-)CHOP protocol<br>* Patients with a persistently positive interim-PET scan assigned to arm B1 will receive another six cycles of the (R-)CHOP regimen (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone).<br>|
| Experimental: B2<br>Six blocks of the B-ALL protocol. | Drug: B-ALL protocol<br>* Patients with a persistently positive interim-PET scan assigned to arm B2 will receive six blocks of the B-ALL protocol (rituximab, methotrexate, ifosfamide, etoposide, cytarabine, vincristine, cyclophosphamide, doxorubicine, vindesine, dexamethasone).<br>|
| Active Comparator: A1<br>Four cycles of the (R-)CHOP regimen. | Drug: (R-)CHOP protocol<br>* Patients with a negative interim-PET scan assigned to arm A1 will receive another four cycles of the (R-)CHOP regimen (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone). Arm A1 was closed when the number of patients required for the randomisation between arms A1 and A2 was reached.<br>|
| Active Comparator: A2<br>Four cycles of the (R-)CHOP regimen plus two additional doses rituximab. | Drug: (R-)CHOP protocol<br>* Patients with a negative interim-PET scan assigned to arm A2 will receive another four cycles of the (R-)CHOP regimen (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone) plus two additional doses rituximab. Since the number of patients required for the randomisation between arms A1 and A2 has been reached, all patients with a negative interim-PET scan are treated according to arm A2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment failure |  | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate, overall survival, disease-free survival, toxicity, quality of life |  | Two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aggressive non-Hodgkin's lymphoma, Positron emission tomography, Chemotherapy