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

NCT ID: NCT01827605

Last Updated: 2023-12-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

159 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2024-01-31

Brief Summary

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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

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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)

Conditions

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Relapsed Follicular Lymphoma

Keywords

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Relapsed follicular Lymphoma RIT Zevalin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A RIT

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.

Group Type EXPERIMENTAL

ZEVALIN

Intervention Type 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).

ARM B ASCT

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

Group Type EXPERIMENTAL

BEAM

Intervention Type 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

Interventions

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ZEVALIN

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).

Intervention Type OTHER

BEAM

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

Intervention Type DRUG

Other Intervention Names

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RIT ASCT

Eligibility Criteria

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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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Umberto Vitolo

Role: PRINCIPAL_INVESTIGATOR

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

Marco Ladetto

Role: PRINCIPAL_INVESTIGATOR

AO SS. Antonio e Biagio e Cesare Arrigo Alessandria

Locations

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A.O.U. San Martino

Genova, GE, Italy

Site Status

Ematologia, A.O. San Gerardo

Monza, Milano, Italy

Site Status

A.O. Niguarda

Milan, MI, Italy

Site Status

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

Rionero in Vulture, Potenza, Italy

Site Status

Azienda Ospedaliera "Bianchi Melacrino Morelli"

Reggio Calabria, RC, Italy

Site Status

Presidio Ospedaliero "A. Tortora"

Pagani, SA, Italy

Site Status

Emat Univ - Città della salute e della scienza di Torino

Torino, TO, Italy

Site Status

Ospedale San Bortolo

Vicenza, VI, Italy

Site Status

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

Verona, VR, Italy

Site Status

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

Alessandria, , Italy

Site Status

Clinica di ematologia AOU Umberto I Ospedali Riuniti

Ancona, , Italy

Site Status

Ematologia con Trapianto Policlinico Universitario Consorziale

Bari, , Italy

Site Status

Spedali Civili

Brescia, , Italy

Site Status

Presidio Ospedaliero A.Perrino - Divisione di Ematologia

Brindisi, , Italy

Site Status

Divisione di Ematologia Osp. Businco

Cagliari, , Italy

Site Status

IRCC Onco-Ematologia

Candiolo, , Italy

Site Status

Ospedale Ferrarotto

Catania, , Italy

Site Status

Policlinico Careggi Clinica Ematologica

Florence, , Italy

Site Status

A O Papardo

Messina, , Italy

Site Status

Ematologia e Trapianto IRCCS, Istituto Nazionale dei Tumori

Milan, , Italy

Site Status

IRCCS San Raffaele Unità di Chemioterapia

Milan, , Italy

Site Status

Policlinico di Modena - Università degli studi

Modena, , Italy

Site Status

Istituto Pascale Oncoematologia

Napoli, , Italy

Site Status

SCDU Ematologia - Università del Piemonte Orientale

Novara, , Italy

Site Status

Ospedale S. Francesco

Nuoro, , Italy

Site Status

Azienda Ospedaliera V. Cervello

Palermo, , Italy

Site Status

U.O. Complessa di Ematologia Ospedale di Parma

Parma, , Italy

Site Status

Ematologia Policlinico San Matteo

Pavia, , Italy

Site Status

Ospedale Santa Maria della Misericordia

Perugia, , Italy

Site Status

Ospedale Santo Spirito Dipartimento di Ematologia

Pescara, , Italy

Site Status

Unità Ematologia Ospedale Civile di Piacenza

Piacenza, , Italy

Site Status

Ausl Ravenna

Ravenna, , Italy

Site Status

SC Ematologia AO Santa Maria Nuova IRCCS

Reggio Emilia, , Italy

Site Status

Univeristà La Sapienza

Roma, , Italy

Site Status

SC Ematologia Città della salute e della scienza di Torino

Torino, , Italy

Site Status

Filippo Gherlizoni

Treviso, , Italy

Site Status

UO Ematologia Osp. Cardinale Panico

Tricase, , Italy

Site Status

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

Udine, , Italy

Site Status

Countries

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Italy

Other Identifiers

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FIL_FLAZ-12

Identifier Type: -

Identifier Source: org_study_id