Sponsor
Gruppo Italiano Terapie Innovative nei Linfomi (G.I.T.I.L.)
Principal Investigator
Dr. Andrea Gallamini S.C. Ematologia Az. Ospedaliera S. Croce e Carle, Cuneo
Protocol Coordinators
Dr. Alessandro Rambaldi Dr. Andrea Gallamini
Coordinating Centre
S.C. Ematologia Azienda Ospedaliera S. Croce e Carle Via M. Coppino, 26 – 12100 Cuneo AIL Phone +39 0171 642414- 642937 – 641070 FAX +39 0171 642937 E-mail
[email protected]
Writing committee
Andrea Gallamini, Alessandro Rambaldi, Corrado Tarella Massimo Gianni, Alberto Biggi, Stephan Chuvie, Anna Di Russo, Roberto Marchioli
CRO
Operations Office: Laboratory of Clinical Epidemiology of NEGRISUD Institute
Multicentre clinical study with early treatment intensification in patients with high risk Hodgkin lymphoma, identified as FDG-PET positive after two conventional ABVD courses (HD 0607 study)
Menton, April 9°, 2010
NIH registration code: NCT00795613
Interim PET in ABVD-treated HL patients
Gallamini, A. et al. J Clin Oncol; 25:3746-3752 2007
2-y PFS according to PET results (164 pts)
PET response-adapted clinical trials in advanced-stage HL 1. Positron Emission Tomography (PET)-Adapted Chemotherapy In Advanced Hodgkin Lymphoma (GITIL HD 0607). http://www.clinicaltrials.gov/ct2/show/NCT00795613 2. Fludeoxyglucose F 18-PET/CT Imaging in Assessing Response to Chemotherapy in Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Hodgkin Lymphoma (RATHL) http://www.clinicaltrials.gov/ct2/show/NCT00678327. 3. High-Dose Chemotherapy and Stem Cell Transplantation, in Patients PET-2 Positive, After 2 Courses of ABVD (IIL HD 0802) and Comparison of RT Versus no RT in PET-2 Negative Patients (IIL HD 0801). http://www.clinicaltrials.gov/ct2/show/NCT00784537. 4. HD18 for Advanced Stages in Hodgkins LymphomaHD18 for Advanced Stages in Hodgkins Lymphoma. (GHSG HD 18) http://www.clinicaltrials.gov/ct2/show/NCT00515554 5. Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma.(SWOG/CALGB USA Intergroup Trial) http://clinicaltrials.gov/ct2/show/NCT00822120
PET response-adapted clinical trials in advanced-stage HL 1. Positron Emission Tomography (PET)-Adapted Chemotherapy In Advanced Hodgkin Lymphoma (GITIL HD 0607). http://www.clinicaltrials.gov/ct2/show/NCT00795613 2. Fludeoxyglucose F 18-PET/CT Imaging in Assessing Response to Chemotherapy in Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Lymphoma (RATHL) 1. Hodgkin Positron Emission Tomography (PET)-Adapted http://www.clinicaltrials.gov/ct2/show/NCT00678327. Chemotherapy In Advanced Hodgkin Lymphoma (HL) 3. High-Dose Chemotherapy and Stem Cell Transplantation, in Patients PET-2 Positive, (GITILAfter HD2 Courses 0607).of ABVD (IIL HD 0802) and Comparison of RT Versus no RT in PET-2 Negative Patients (IIL HD 0801). http://www.clinicaltrials.gov/ct2/show/NCT00795613 http://www.clinicaltrials.gov/ct2/show/NCT00784537. 4. HD18 for Advanced Stages in Hodgkins LymphomaHD18 for Advanced Stages in Hodgkins Lymphoma. (GHSG HD 18) http://www.clinicaltrials.gov/ct2/show/NCT00515554 5. Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma.(SWOG/CALGB USA Intergroup Trial) http://clinicaltrials.gov/ct2/show/NCT00822120
Endpoints
Primary endpoint
3-year progression free survival (PFS) of the entire cohort of patients .
Secondary endpoints
- 3-year event free survival (EFS) of all the registered patients, whatever the treatment assigned. Events are deaths from any cause, disease progression, secondary cancer, late serious treatment-related events. - Feasibility of the program for the entire population of advanced-stage HL patients admitted to GITIL institutions
Inclusion criteria Inclusion criteria
• Patients with advanced classical Hodgkin Lymphoma according to the WHO classification • Aged 18-60 • Not previously treated • Stages IIB to IV B • All IPS prognostic groups • Patients who have signed an informed consent form
Exclusion criteria
• Patients aged more than 60. • Concomitant or previously treated neoplastic disorder less than 5 year before the diagnosis of Hodgkin’s lymphoma. • Psychiatric disorders • Uncontrolled infectious disease • Impaired cardiac (EF < 50%) , renal (creatinine clearance < 60 ml/m)HIV, • HBV DNA, HCV RNA positive markers • Pregnancy and lactation • Patients with uncompensated diabetes mellitus and fasting glucose levels over 200 mg/dl
Geographic Geographic distribution distribution of of participating participating Centers Centers
NIH registration code: NCT00795613
CMNS
23 23 centers centers
23 23 active active centers centers 33 center center waiting waiting for for approval approval by by CE CE
ABVD x 2
HD IIB-IV B stage
GITIL GITILHD0607 HD0607 Protocol Protocol
CT-PET
R BEACOPP-esc. x 4
-
+
ABVD x 4 R-BEACOPP-esc. x 4
CT-PET
CT-PET
BEACOPP-bas. x 4
-
+ -
+
(Biopsy +)
Allo-SC available (n/y)
R-BEACOPP-bas. x 4
IGEV x 4 + ASCT
R
No Consolidation Rx therapy Double ASCT
CT-PET
Consolidation Rx therapy
ASCT + Allo-RIC
Assess response on completion of treatment
CT-PET
Follow up until death
Central panel for PET reviewing PET-centre of the GITIL Institution (X)
PET-2 (positive or minimally positive) & PET-0
Reviewer 1
Reviewer 2
Reviewer 3
Reviewer 4
Reviewer 5
Reviewer 6
Reviewer 7
Pos./ neg.
Pos./ neg.
Within three days Pos./ neg.
Pos./ neg.
Pos./ neg.
Pos./ neg.
Pos./ neg.
First three incoming replies: PET-2 positive or negative
INFN Website
Clinical Centre GITIL (X)
CRO
PET center uploads PET0 & PET-2 (positive or minimally positive) on the dedicated WEBsite of INFN of Turin
PET review panel
E-mail & SMS every 6h
72h First 3 replies
Clinical Center
RANDOMIZING
https://heart.negrisud.it/HD/
CMNS
ooff d r eer aannd t t n e en ic C Ce nttiiffic raattiivve n e n tr sscciie iinniisst naattiioon m iin dm orrd aad d ccooo
Patient enrolment (30.03.2010)
First 100 enrolled patients (30.03.2010)
(100)ENROLLED (2) MISSING
(98)INITIAL THERAPY (ABVD x 2) (1) Ongoing
(96)COMPLETED
(1) OUT - PD
ABVD x 2
(96)INTERIM STAGING CT-PET 2
(23) PET-2 Pos
(73) PET-2 Neg
Interim-PET positive patients (30.03.2010) (23) PET-2 Pos (11) esc. BEACOPP
(12) esc. R-BEACOPP (3) End of Study
(2) Refusal (1) PD
(11) Ongoing
(9) PET 3 (after 4 esc BEACOPP)
(1) PET-3 Pos
(8) PET-3 Neg
(1) DHAP
(8) [R] BEACOPP bs
(4) FINAL RESTAGING
Interim-PET negative patients (30.03.2010) (73) PET-2 Neg (12)MISSING
(61) ABVD x 4 (14) Ongoing (2) End of Study
(45) CT-PET 3
(5) PET-3 Pos
(40) PET-3 Neg
(4) MISSING
(11) RX NO
(1) HDS Therapy (17)Bulky No
(12) RX YES
(5) MISSING
(33) FINAL RESTAGING
(2) Refusal
Concordance rate among six reviewers (N=47: 30.03.10) Mean
U.F.
F.F.
A.B.
U.G.
F.C
M.G
U.F.
0.66
1
0.84
0.70
0.63
0.53
0.74
F.F.
0.89
0.84
1
0.94
0.66
0.84
0.84
A.B.
0.64
0.70
0.94
1
0.58
0.72
0.88
U.G.
0.51
0.63
0.66
0.58
1
0.63
0.58
Substantial
F.C.
0.57
0.53
0.84
0.72
0.63
1
0.68
Moderate
M.G.
0.62
0.74
0.84
0.88
0.58
0.68
1
CONCORDANCE Almost perfect
k Cohen coefficient
2nd Investigator meeting: Capri, 19.03.2010
