HD0801: 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

Sponsor

Fondazione Italiana Linfomi ONLUS (Other)

Overall Status

Completed

CT.gov ID

NCT00784537

Collaborator

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

520

Enrollment

Locations

Arms

Duration (Months)

19.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin's Lymphoma	Drug: ABVD Drug: ABVD and Radiotherapy	Phase 2/Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

520 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2008

Actual Primary Completion Date :

Jan 1, 2015

Actual Study Completion Date :

Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Other: 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.	Drug: 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)
Other: 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.	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).

Arm

Intervention/Treatment

Other: 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.

Drug: 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)

Other: Arm B

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).

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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%).

Contacts and Locations

Locations

	Site	City	Country
1	Centro di riferimento Oncologico Oncologia Medica A	Aviano	Italy
2	Università Policlinico di Bari - Divisione di Medicina A	Bari	Italy
3	Policlinco Sant'Orsola Isituto di Ematologia ed oncologia Medica	Bologna	Italy
4	Sezione di Ematologia Spedali Civili	Brescia	Italy
5	Ospedale di Circolo SC Oncologia Medica III	Busto Arsizio	Italy
6	Divisione di Ematologia Osp.Businco	Cagliari	Italy
7	Policlinico Careggi Cattedra di Ematologia	Firenze	Italy
8	ASLTO4	Ivrea	Italy
9	Osp. Cardinale Panico Divisione di Ematologia Tricase	Lecce	Italy
10	Ospedale Niguarda Cà Granda	Milano	Italy
11	Università Avogadro Divisione di Ematologia	Novara	Italy
12	Ospedale San Francesco UO Ematologia e Centro Trapianti	Nuoro	Italy
13	Fondazione Policlinico San Matteo Clinica Ematologica	Pavia	Italy
14	Osp. Santa Maria delle Croci UO Ematologia	Ravenna	Italy
15	Ospedale Bianchi Melacrino Morelli	Reggio Calabria	Italy
16	Osp. degli Infermi Divisione di Oncologia	Rimini	Italy
17	Istituto Regina Elena IFO SC Ematologia	Roma	Italy
18	Osp.Sant'Eugenio Divisione di Ematologia	Roma	Italy
19	Università La Sapienza Dipartimento di Biotecnnologie Cellulari	Roma	Italy
20	Istituto Clinico Humanitas Divisione di Oncologia Medica ed Ematologia	Rozzano (MI)	Italy
21	AO Universitaria di Sassari	Sassari	Italy
22	Policlinico Le Scotte	Siena	Italy
23	Struttura Complessa di Onco-Ematologia	Terni	Italy
24	IRCC Onco-Ematologia Candiolo	Torino	Italy
25	Osp. San Giovanni Battista_Molinette Ematologia 2	Torino	Italy
26	Azienda Ospedaliero universitaria di Udine	Udine	Italy
27	ASL 14 UO Oncologia	Verbania	Italy