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

NCT ID: NCT00784537

Last Updated: 2018-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 520 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2016-01-31

Brief Summary

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

This study is composed by two phases:

1. 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).

2. 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.

Conditions

Hodgkin's Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

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.

Group Type: OTHER

ABVD

Intervention Type: DRUG

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)

Arm B

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.

Group Type: OTHER

ABVD and Radiotherapy

Intervention Type: DRUG

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).

Interventions

ABVD

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)

Intervention Type: DRUG

ABVD and Radiotherapy

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).

Intervention Type: DRUG

Eligibility Criteria

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%).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

OTHER

Sponsor Role: collaborator

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alessandro Levis, MD

Role: STUDY_DIRECTOR

Ospedale SS. Antonio, Biagio e Cesare Arrigo

Locations

Centro di riferimento Oncologico Oncologia Medica A

Aviano, , Italy

Università Policlinico di Bari - Divisione di Medicina A

Bari, , Italy

Policlinco Sant'Orsola Isituto di Ematologia ed oncologia Medica

Bologna, , Italy

Sezione di Ematologia Spedali Civili

Brescia, , Italy

Ospedale di Circolo SC Oncologia Medica III

Busto Arsizio, , Italy

Divisione di Ematologia Osp.Businco

Cagliari, , Italy

Policlinico Careggi Cattedra di Ematologia

Florence, , Italy

ASLTO4

Ivrea, , Italy

Osp. Cardinale Panico Divisione di Ematologia Tricase

Lecce, , Italy

Ospedale Niguarda Cà Granda

Milan, , Italy

Università Avogadro Divisione di Ematologia

Novara, , Italy

Ospedale San Francesco UO Ematologia e Centro Trapianti

Nuoro, , Italy

Fondazione Policlinico San Matteo Clinica Ematologica

Pavia, , Italy

Osp. Santa Maria delle Croci UO Ematologia

Ravenna, , Italy

Ospedale Bianchi Melacrino Morelli

Reggio Calabria, , Italy

Osp. degli Infermi Divisione di Oncologia

Rimini, , Italy

Istituto Regina Elena IFO SC Ematologia

Roma, , Italy

Osp.Sant'Eugenio Divisione di Ematologia

Roma, , Italy

Università La Sapienza Dipartimento di Biotecnnologie Cellulari

Roma, , Italy

Istituto Clinico Humanitas Divisione di Oncologia Medica ed Ematologia

Rozzano (MI), , Italy

AO Universitaria di Sassari

Sassari, , Italy

Policlinico Le Scotte

Siena, , Italy

Struttura Complessa di Onco-Ematologia

Terni, , Italy

IRCC Onco-Ematologia Candiolo

Torino, , Italy

Osp. San Giovanni Battista_Molinette Ematologia 2

Torino, , Italy

Azienda Ospedaliero universitaria di Udine

Udine, , Italy

ASL 14 UO Oncologia

Verbania, , Italy

Countries

Italy

References

Kreuzberger N, Goldkuhle M, von Tresckow B, Kobe C, Sickinger MT, Monsef I, Skoetz N. Positron emission tomography-adapted therapy for first-line treatment in adults with Hodgkin lymphoma. Cochrane Database Syst Rev. 2025 Mar 26;3(3):CD010533. doi: 10.1002/14651858.CD010533.pub3.

Reference Type: DERIVED

PMID: 40135712 (View on PubMed)

Ricardi U, Levis M, Evangelista A, Gioia DM, Sacchetti GM, Gotti M, Re A, Buglione M, Pavone V, Nardella A, Nassi L, Zanni M, Franzone P, Frezza GP, Pulsoni A, Grapulin L, Santoro A, Rigacci L, Simontacchi G, Tani M, Zaja F, Abruzzese E, Botto B, Zilioli VR, Rota-Scalabrini D, Freilone R, Ciccone G, Filippi AR, Zinzani PL. Role of radiotherapy to bulky sites of advanced Hodgkin lymphoma treated with ABVD: final results of FIL HD0801 trial. Blood Adv. 2021 Nov 9;5(21):4504-4514. doi: 10.1182/bloodadvances.2021005150.

Reference Type: DERIVED

PMID: 34597375 (View on PubMed)

Zinzani PL, Broccoli A, Gioia DM, Castagnoli A, Ciccone G, Evangelista A, Santoro A, Ricardi U, Bonfichi M, Brusamolino E, Rossi G, Anastasia A, Zaja F, Vitolo U, Pavone V, Pulsoni A, Rigacci L, Gaidano G, Stelitano C, Salvi F, Rusconi C, Tani M, Freilone R, Pregno P, Borsatti E, Sacchetti GM, Argnani L, Levis A. Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study. J Clin Oncol. 2016 Apr 20;34(12):1376-85. doi: 10.1200/JCO.2015.63.0699. Epub 2016 Feb 16.

Reference Type: DERIVED

PMID: 26884559 (View on PubMed)

Other Identifiers

EudracT Number 2008-002684-14

Identifier Type: -

Identifier Source: secondary_id

IIL-HD0801

Identifier Type: -

Identifier Source: org_study_id