High-dose Chemotherapy and Stem Cell Transplantation, in Patients PET-2 Positive, After 2 Courses of ABVD and Comparison of RT Versus no RT in PET-2 Negative Patients

Study Overview
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Brief Summary
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The purpose of this study is to define an improvement in patients: To evaluate if patients resistant to the initial treatment for residual PET-positive masses after the first two courses of ABVD (PET-2 positive), can be salvaged by early shift to high-dose chemotherapy supported by stem cell rescue To analyse if patients achieving early complete response (PET-2 negative), can be spared the adjuvant radiotherapy on areas of initial bulky disease, at the end of the planned six courses of ABVD. To answer this question, PET-2 negative patients will be randomized between radiotherapy versus no radiotherapy at the end of ABVD therapy.

Detailed Description
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This study is composed by two phases: A phase II multi-centre study evaluating in patients with advanced stage Hodgkin lymphoma the efficacy of an early salvage treatment with high-dose chemotherapy followed by stem cell transplantation in patients FDG-PET positive after two courses of ABVD (PET-2 positive). A phase III randomised study comparing the efficacy of radiotherapy to the areas of initial bulky disease versus no further therapy in PET-2 negative patients in complete remission (PET-6 negative) at the end of six courses of ABVD.

Official Title
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Early Salvage With High Dose Chemotherapy and Stem Cell Transplantation in Advanced Stage Hodgkin's Lymphoma Patients With Positive PET After Two Courses of ABVD (PET-2 Positive) and Comparison of RT Versus no RT in PET-2 Negative Patients

Conditions
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Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: ABVD
* Drug: ABVD and Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed Hodgkin's lymphoma of the classical type (nodular lymphocyte predominance excluded). Stage IIB-IV. Age 18-70. No prior therapy for Hodgkin's lymphoma Written informed consent. ECOG performance status grades 0-3 (see Appendix E). FDG-PET scan before the initiation of treatment. Exclusion Criteria: Prior therapy for Hodgkin's lymphoma. Age less than 18 or more than 70. Other concomitant or prior malignancies, except basal cell skin carcinoma, or adequately treated carcinoma in situ of the cervix, or any cancer in complete remission for more than 5 years. HIV infection. Pregnancy or breast-feeding. Renal failure (creatinine ≥2 times the normal value), liver failure (AST/ALT or bilirubine ≥ 2.5 times the normal value) or heart failure (NYHA class ≥ 2 or FEV < 45%).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- | --- |
| Other: Arm A<br>Two courses of ABVD. Early restaging with FDG-PET scan (PET-2) The subsequent treatment will be as it follows: PET-2 positive patients will be high-dose salvage treatment; PET-2 negative patients will be treated with four additional courses of ABVD (for a total of six courses). The following restaging procedures are planned as it follows: Optional: Whole body CT scan after the fourth course of ABVD; no therapy change will be made according to CT scan. Mandatory: Whole body CT and FDG-PET scans after the sixth course of ABVD (PET-6). PET-6 negative patients will be randomized to first arm: No radiotherapy. | Drug: ABVD<br>* ABVD courses are scheduled every 28 days: Doxorubicin 25 mg/m2 i.v. day 1 and 15 Bleomycin 10 mg/m2 i.v. day 1 and 15 Vinblastine 6 mg/m2 i.v. day 1 and 15 Dacarbazine 375 mg/m2 i.v. day 1 and 15 ABVD courses are scheduled every 28 days: Doxorubicin 25 mg/m2 i.v. day 1 and 15 Bleomycin 10 mg/m2 i.v. day 1 and 15 Vinblastine 6 mg/m2 i.v. day 1 and 15 Dacarbazine 375 mg/m2 i.v. day 1 and 15 Randomization to Arm A (Observation)<br>|
| Other: Arm B<br>Two courses of ABVD. Early restaging with FDG-PET scan (PET-2) The subsequent treatment will be as it follows: PET-2 positive patients will be high-dose salvage treatment; PET-2 negative patients will be treated with four additional courses of ABVD (for a total of six courses). The following restaging procedures are planned as it follows: Optional: Whole body CT scan after the fourth course of ABVD; no therapy change will be made according to CT scan. Mandatory: Whole body CT and FDG-PET scans after the sixth course of ABVD (PET-6). PET-6 negative patients will be randomized to second arm: Adjuvant radiotherapy (30 Gy) on sites of initial bulky disease. | Drug: ABVD and Radiotherapy<br>* ABVD courses are scheduled every 28 days: Doxorubicin 25 mg/m2 i.v. day 1 and 15 Bleomycin 10 mg/m2 i.v. day 1 and 15 Vinblastine 6 mg/m2 i.v. day 1 and 15 Dacarbazine 375 mg/m2 i.v. day 1 and 15 Randomization to Arm B, Radiotherapy, in patients in CR, on the area of initial bulky disease (see above for the definition of nodal and/or mediastinal bulk).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate if patients resistant to the initial treatment for residual PET-positive masses after the first two courses of ABVD (PET-2 positive), can be salvaged by early shift to high-dose chemotherapy supported by stem cell rescue. |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To analyse if patients achieving early complete response (PET-2 negative), can be spared the adjuvant radiotherapy on areas of initial bulky disease, at the end of the planned six courses of ABVD. |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hodgkin's lymphoma, ABVD, FDG-PET (18-Fluoro-deoxy-D-glucose Positron Emission Tomography), Radiotherapy