A Phase III Multicenter, Randomized Study Comparing RIT Vs ASCT in Patients With Relapsed/Refractory (FL)

NCT01827605 | Unknown Phase 3

• 1 other identifier: FIL_FLAZ-12
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 38

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.

Conditions

Relapsed Follicular Lymphoma

Keywords

Relapsed follicular Lymphoma; RIT; Zevalin

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival from randomization (rPFS)

  PFS will be defined as the time between the date of randomization and the date of disease progression, relapse or death from any cause.

  36 months

Secondary Outcomes (11)

• Overall Survival from randomization (rOS)

  36 months

• Event Free Survival (EFS)

  36 months

• Treatment Free Survival from randomization (TFS)

  36 months

• Progression Free Survival from enrolment (ePFS)

  42 months

• Overall Survival from enrolment (eOS)

  42 months

Study Arms (2)

Arm A RIT

EXPERIMENTAL

Infusion of 90Y Ibritumomab Tiuxetan if the patient has less than 25% BM infiltration at the pre-consolidation restaging (0.4 mCi/kg if platelets ≥150,000/mmc, 0.3 mCi/kg if platelets are between 100.000 and 150,000/mmc). Zevalin® will be delivered as per indications and should thus be provided at expenses following regular supplies procedures.

Other: ZEVALIN

ARM B ASCT

EXPERIMENTAL

BEAM conditioning regimen (or in alternative FEAM regimen with fotemustine to replace BCNU) and reinfusion of CD34+ cells of ≥ 2x106/Kg CD34+ day 0 (optimal dose to reinfuse 4x106/Kg CD34+). G-CSF 5 mcg/Kg from day 2 until ANC\>1500/mmc. Patients who failed mobilization will directly proceed to rituximab maintenance

Drug: BEAM

Interventions

ZEVALIN OTHER

Infusion of 90Y Ibritumomab Tiuxetan if the patient has less than 25% BM infiltration at the pre-consolidation restaging (0.4 mCi/kg if platelets ≥150,000/mmc, 0.3 mCi/kg if platelets are between 100.000 and 150,000/mmc).

Also known as: RIT

Arm A RIT

BEAM DRUG

BEAM REGIMEN day -6 Carmustine\* 300 mg/ m2 i.v. in 250ml dextrose 5% solution from day -5 to day -2 Cytarabine 200 mg/m2 i.v. every 12 hours in 250 ml dextrose 5% solution, 250 ml/hr Etoposide 100 mg/m2 i.v. every 12 hours in 250 ml dextrose 5% solution, 250 ml/hr day -1 Melphalan 140 mg/m2 i.v. in 100ml saline solution in 200 ml/hr day 0 UReinfusion of autologous stem cells following this rules: 1. Patient collecting ≥6x106 CD34+ cells/kg use \>4x106 CD34+ cells/kg for ASCT and keep \>2x106 CD34+ cells/kg for back up; 2. Patient collecting 4-6x106 CD34+ cells/kg use \>2x106 CD34+ cells/kg for ASCT and keep \>2x106 CD34+ cells/kg for back up; 3. Patient collecting 2-4x106 CD34+ cells/kg use all CD34+ cells for ASCT and keep no back up. day 2 Filgrastim or Lenograstim 5μg/Kg s.c. until ANC \> 1500/mmc

Also known as: ASCT

ARM B ASCT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Signed informed written consent
• 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
• 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

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (38)

A.O.U. San Martino

Genova, GE, 16132, Italy

Location

Ematologia, A.O. San Gerardo

Monza, Milano, 20052, Italy

Location

A.O. Niguarda

Milan, MI, 20162, Italy

Location

IRCCS-Centro di riferimento oncologico UO di ematologia e Trapianto Cellule Staminali

Rionero in Vulture, Potenza, 85028, Italy

Location

Azienda Ospedaliera "Bianchi Melacrino Morelli"

Reggio Calabria, RC, 89125, Italy

Location

Presidio Ospedaliero "A. Tortora"

Pagani, SA, 84014, Italy

Location

Emat Univ - Città della salute e della scienza di Torino

Torino, TO, 10126, Italy

Location

Ospedale San Bortolo

Vicenza, VI, 36100, Italy

Location

Ospedale Policlinico G.B. Rossi (Borgo Roma) Di Verona

Verona, VR, 37126, Italy

Location

A.O. SS. Antonio e Biagio e C. Arrigo

Alessandria, 15121, Italy

Location

Clinica di ematologia AOU Umberto I Ospedali Riuniti

Ancona, 60100, Italy

Location

Ematologia con Trapianto Policlinico Universitario Consorziale

Bari, 70124, Italy

Location

Spedali Civili

Brescia, Italy

Location

Presidio Ospedaliero A.Perrino - Divisione di Ematologia

Brindisi, Italy

Location

Divisione di Ematologia Osp. Businco

Cagliari, Italy

Location

IRCC Onco-Ematologia

Candiolo, Italy

Location

Ospedale Ferrarotto

Catania, Italy

Location

Policlinico Careggi Clinica Ematologica

Florence, Italy

Location

A O Papardo

Messina, Italy

Location

Ematologia e Trapianto IRCCS, Istituto Nazionale dei Tumori

Milan, Italy

Location

IRCCS San Raffaele Unità di Chemioterapia

Milan, Italy

Location

Policlinico di Modena - Università degli studi

Modena, Italy

Location

Istituto Pascale Oncoematologia

Napoli, Italy

Location

SCDU Ematologia - Università del Piemonte Orientale

Novara, 28100, Italy

Location

Ospedale S. Francesco

Nuoro, Italy

Location

Azienda Ospedaliera V. Cervello

Palermo, 90146, Italy

Location

U.O. Complessa di Ematologia Ospedale di Parma

Parma, 43100, Italy

Location

Ematologia Policlinico San Matteo

Pavia, 27100, Italy

Location

Ospedale Santa Maria della Misericordia

Perugia, Italy

Location

Ospedale Santo Spirito Dipartimento di Ematologia

Pescara, Italy

Location

Unità Ematologia Ospedale Civile di Piacenza

Piacenza, 29100, Italy

Location

Ausl Ravenna

Ravenna, Italy

Location

SC Ematologia AO Santa Maria Nuova IRCCS

Reggio Emilia, 42123, Italy

Location

Univeristà La Sapienza

Roma, Italy

Location

SC Ematologia Città della salute e della scienza di Torino

Torino, Italy

Location

Filippo Gherlizoni

Treviso, Italy

Location

UO Ematologia Osp. Cardinale Panico

Tricase, Italy

Location

Clinica di Ematologia - A.O.U. S. Maria di Udine

Udine, Italy

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

ibritumomab tiuxetan

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Umberto Vitolo

  AO Città della salute e della Scienza di Torino - Ospedale S. Giovanni Battista - TORINO

  PRINCIPAL INVESTIGATOR

• Marco Ladetto

  AO SS. Antonio e Biagio e Cesare Arrigo Alessandria

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2013
• First Posted: April 9, 2013
• Study Start: January 1, 2012
• Primary Completion: October 1, 2019
• Study Completion: January 1, 2024
• Last Updated: December 14, 2023

Record last verified: 2023-12

Locations

IT (38)