Clinical trial NCT01827605: A Phase III Multicenter, Randomized Study Comparing RIT Vs ASCT in Patients With Relapsed/Refractory (FL)
Official title: A Phase III Multicenter,Randomized Study Comparing Consolidation With 90yttrium-Labeled Ibritumomab Tiuxetan (Zevalin®) Radioimmunotherapy Vs Autologous Stem Cell Transplantation (ASCT) in Patients With Relapsed/Refractory Follicular Lymphoma (FL) Aged 18-65 Years
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Relapsed Follicular Lymphoma
Keywords: Relapsed follicular Lymphoma
RIT
Zevalin
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2013-04-09
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase III, multicenter, open-label, randomized and controlled study to compare the efficacy of a consolidation therapy with RIT versus ASCT in patients with FL in CR or PR after second or third line chemotherapy supplemented with rituximab.

Detailed description: This is a Phase III, multicenter, open-label, randomized and controlled study to compare the efficacy of a consolidation therapy with RIT vs. ASCT in patients with FL in CR or PR after second or third line chemotherapy supplemented with rituximab. Patients with FL will be eligible for screening at the time of relapsed or refractory disease after two or less chemotherapy lines at least one containing rituximab.

This study will be conducted in six steps as follows. Screening Phase, Enrolment and Induction chemotherapy (STEP I) Randomization (STEP II) Stem cell mobilization and collection (STEP III) Consolidation (RIT vs ASCT) (STEP IV) Maintenance (STEP V) Follow-up Phase (STEP VI)

Eligibility criteria: Inclusion Criteria:

* Age 18-65
* Histologically documented diagnosis of grade I-IIIa FL defined according to WHO guidelines 2008 (Re-biopsy required)
* Availability of BM and PB for Minimal Residual Disease (MRD) analysis (see Appendix I)
* Relapsed or refractory disease after ≤ two chemotherapy lines at least one containing Rituximab (Rituximab maintenance is UNOTU considered a therapeutic line)
* Clinical indication of treatment i.e. Stage II-IV who require therapy according to SIE and GELF criteria (see Appendix II)
* ECOG performance status 0-2 (unless disease-related) (see Appendix III)
* Availability of histological material for centralized revision
* Laboratory values:

  * ANC ≥ 1500/mmc unless due to marrow involvement by lymphoma and/or platelets ≥ 100000/mmc unless due to marrow involvement by lymphoma
  * Serum creatinine ≤ 1.5 x ULN, unless it is disease related
  * Bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN, if patient has Gilbert syndrome)
  * AST/SGOT and/or ALT/SGPT ≤ 2.5 x ULN if not lymphoma related or ≤ 5.0 x ULN in case of lymphoma liver involvement
* Adequate cardiac function: LVEF \> 50% by echocardiography or MUGA scan
* Not pregnant or breast-feeding
* Willingness to use effective contraception during the study and 3 months after the end of treatment
* No other prior malignancies except for adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or other cancer from which the patient has been disease-free for ≥ 5 years (see Exclusion criteria 14)
* Signed informed written consent

Exclusion Criteria:

* Grade IIIb FL, transformed FL or histologies different from FL
* Previous treatment with \> two lines of chemotherapy ± rituximab Maintenance is UNOTU considered a therapeutics line)
* Previous ASCT or RIT treatment
* CNS involvement by lymphoma
* HBV positivity with the exception of patients who are seropositive because of hepatitis B virus vaccination and patients HbcAb positive and HbsAg negative with undetectable serum HBV-DNA. Occult carriers: must receive treatment with Lamivudine 100 mg for the duration of treatment program and at least 12 months after treatment cessation; HBV-DNA levels and HBsAg will be monitored every month
* HCV positivity with elevated transaminases or INR or APTT or active virus replication
* HIV positivity
* Any concurrent medical condition requiring long term use (\> one month) of systemic corticosteroids
* Active bacterial, viral, or fungal infection requiring systemic therapy
* Any concurrent medical or psychiatric condition which might impair administration of therapy or preclude the ability to give informed consent
* Treatment with an experimental agent within 30 days prior to study entry
* Myelosuppressive chemo or biological therapy within three weeks before study entry (use rituximab course delivered as maintenance is not an exclusion therapy)
* Major surgery other than diagnosis within 4 weeks prior to study entry
* Previous i.v. or i.m. treatments with murine or animal derived antibodies

Primary outcomes:
measure: Progression Free Survival from randomization (rPFS)
timeFrame: 36 months
Secondary outcomes:
measure: Overall Survival from randomization (rOS)
timeFrame: 36 months
measure: Event Free Survival (EFS)
timeFrame: 36 months
measure: Treatment Free Survival from randomization (TFS)
timeFrame: 36 months
measure: Progression Free Survival from enrolment (ePFS)
timeFrame: 42 months
measure: Overall Survival from enrolment (eOS)
timeFrame: 42 months
measure: Complete Response (CR) Rate
timeFrame: At the end of the consolidation phase (6 months)
measure: Overall Response Rate (ORR)
timeFrame: At the end of the consolidation phase (6 months)
measure: Toxicity
timeFrame: 42 months
measure: Molecular Response rate (MR)
timeFrame: 36 months
measure: Molecular Response rate conversion (cMR)
timeFrame: 6 months
measure: Molecular Relapse Rate (MRR)
timeFrame: 24 months
Other outcomes:
Locations:
city: Genova
country: Italy
facility: A.O.U. San Martino
state: GE
city: Monza
country: Italy
facility: Ematologia, A.O. San Gerardo
state: Milano
city: Milano
country: Italy
facility: A.O. Niguarda
state: MI
city: Rionero in Vulture
country: Italy
facility: IRCCS-Centro di riferimento oncologico UO di ematologia e Trapianto Cellule Staminali
state: Potenza
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera "Bianchi Melacrino Morelli"
state: RC
city: Pagani
country: Italy
facility: Presidio Ospedaliero "A. Tortora"
state: SA
city: Torino
country: Italy
facility: Emat Univ - Città della salute e della scienza di Torino
state: TO
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
state: VI
city: Verona
country: Italy
facility: Ospedale Policlinico G.B. Rossi (Borgo Roma) Di Verona
state: VR
city: Alessandria
country: Italy
facility: A.O. SS. Antonio e Biagio e C. Arrigo
city: Ancona
country: Italy
facility: Clinica di ematologia AOU Umberto I Ospedali Riuniti
city: Bari
country: Italy
facility: Ematologia con Trapianto Policlinico Universitario Consorziale
city: Brescia
country: Italy
facility: Spedali Civili
city: Brindisi
country: Italy
facility: Presidio Ospedaliero A.Perrino - Divisione di Ematologia
city: Cagliari
country: Italy
facility: Divisione di Ematologia Osp. Businco
city: Candiolo
country: Italy
facility: IRCC Onco-Ematologia
city: Catania
country: Italy
facility: Ospedale Ferrarotto
city: Firenze
country: Italy
facility: Policlinico Careggi Clinica Ematologica
city: Messina
country: Italy
facility: A O Papardo
city: Milano
country: Italy
facility: Ematologia e Trapianto IRCCS, Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: IRCCS San Raffaele Unità di Chemioterapia
city: Modena
country: Italy
facility: Policlinico di Modena - Università degli studi
city: Napoli
country: Italy
facility: Istituto Pascale Oncoematologia
city: Novara
country: Italy
facility: SCDU Ematologia - Università del Piemonte Orientale
city: Nuoro
country: Italy
facility: Ospedale S. Francesco
city: Palermo
country: Italy
facility: Azienda Ospedaliera V. Cervello
city: Parma
country: Italy
facility: U.O. Complessa di Ematologia Ospedale di Parma
city: Pavia
country: Italy
facility: Ematologia Policlinico San Matteo
city: Perugia
country: Italy
facility: Ospedale Santa Maria della Misericordia
city: Pescara
country: Italy
facility: Ospedale Santo Spirito Dipartimento di Ematologia
city: Piacenza
country: Italy
facility: Unità Ematologia Ospedale Civile di Piacenza
city: Ravenna
country: Italy
facility: Ausl Ravenna
city: Reggio Emilia
country: Italy
facility: SC Ematologia AO Santa Maria Nuova IRCCS
city: Roma
country: Italy
facility: Univeristà La Sapienza
city: Torino
country: Italy
facility: SC Ematologia Città della salute e della scienza di Torino
city: Treviso
country: Italy
facility: Filippo Gherlizoni
city: Tricase
country: Italy
facility: UO Ematologia Osp. Cardinale Panico
city: Udine
country: Italy
facility: Clinica di Ematologia - A.O.U. S. Maria di Udine
Study officials:
affiliation: AO Città della salute e della Scienza di Torino - Ospedale S. Giovanni Battista - TORINO
name: Umberto Vitolo
role: PRINCIPAL_INVESTIGATOR
affiliation: AO SS. Antonio e Biagio e Cesare Arrigo Alessandria
name: Marco Ladetto
role: PRINCIPAL_INVESTIGATOR
References: