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Relapsed Follicular LymphomaPhase 3NCT01827605

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

A Phase 3 study testing ZEVALIN and BEAM in people with Relapsed Follicular Lymphoma, run by Fondazione Italiana Linfomi - ETS at 38 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Relapsed Follicular Lymphoma
What is being tested?
ZEVALIN and BEAM
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
159 participants
Where
38 sitesItaly
Study dates
Jan 2012to Jan 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

38 sites in 1 country.

38 sites in 1 country

Italy38 sites

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

    Alessandria, Alessandria, 15121

  • Clinica di ematologia AOU Umberto I Ospedali Riuniti

    Ancona, Ancona, 60100

  • Ematologia con Trapianto Policlinico Universitario Consorziale

    Bari, Bari, 70124

  • Spedali Civili

    Brescia, Brescia

  • Presidio Ospedaliero A.Perrino - Divisione di Ematologia

    Brindisi

  • Divisione di Ematologia Osp. Businco

    Cagliari

  • IRCC Onco-Ematologia

    Candiolo

  • Ospedale Ferrarotto

    Catania

  • Policlinico Careggi Clinica Ematologica

    Florence

  • A.O.U. San Martino

    Genova, GE, 16132

  • A O Papardo

    Messina

  • Ematologia e Trapianto IRCCS, Istituto Nazionale dei Tumori

    Milan, Milano

  • A.O. Niguarda

    Milan, MI, 20162

  • IRCCS San Raffaele Unità di Chemioterapia

    Milan

  • Policlinico di Modena - Università degli studi

    Modena

  • Ematologia, A.O. San Gerardo

    Monza, Milano, 20052

  • Istituto Pascale Oncoematologia

    Naples

  • SCDU Ematologia - Università del Piemonte Orientale

    Novara, Novara, 28100

  • Ospedale S. Francesco

    Nuoro

  • Presidio Ospedaliero "A. Tortora"

    Pagani, SA, 84014

  • Azienda Ospedaliera V. Cervello

    Palermo, Italy, 90146

  • U.O. Complessa di Ematologia Ospedale di Parma

    Parma, Parma, 43100

  • Ematologia Policlinico San Matteo

    Pavia, Pavia, 27100

  • Ospedale Santa Maria della Misericordia

    Perugia

  • Ospedale Santo Spirito Dipartimento di Ematologia

    Pescara

  • Unità Ematologia Ospedale Civile di Piacenza

    Piacenza, Piacenza, 29100

  • Ausl Ravenna

    Ravenna

  • Azienda Ospedaliera "Bianchi Melacrino Morelli"

    Reggio Calabria, RC, 89125

  • SC Ematologia AO Santa Maria Nuova IRCCS

    Reggio Emilia, Reggio Emilia, 42123

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

    Rionero in Vulture, Potenza, 85028

  • Univeristà La Sapienza

    Roma

  • Emat Univ - Città della salute e della scienza di Torino

    Torino, TO, 10126

  • SC Ematologia Città della salute e della scienza di Torino

    Torino

  • Filippo Gherlizoni

    Treviso

  • UO Ematologia Osp. Cardinale Panico

    Tricase

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

    Udine

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

    Verona, VR, 37126

  • Ospedale San Bortolo

    Vicenza, VI, 36100

Other trials in Italy

About this study

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

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.

Read the 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)

Being tested
ZEVALIN, BEAM
Keywords
Relapsed follicular Lymphoma, RIT, Zevalin
Medical subject headings
Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZEVALINOther

    Also called 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).

  • BEAMDrug

    Also called ASCT

    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
Study groups in NCT01827605
Study groupRoleWhat they receive
Arm A RITExperimentalInfusion 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.
Receives: Other: ZEVALIN
ARM B ASCTExperimentalBEAM 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
Receives: Drug: BEAM

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 36 months

Secondary outcomes (11)

  1. Overall Survival from randomization (rOS)

    OS will be defined as the time between the date of randomization and the date of death from any cause.

    Measured: 36 months

  2. Event Free Survival (EFS)

    EFS will be measured from the date of randomization to the date of any treatment failure including death, disease progression or relapse, discontinuation of treatment for any reason (toxicity, patient preference, initiation of new treatment without documented progression).

    Measured: 36 months

  3. Treatment Free Survival from randomization (TFS)

    TFS will be defined as the time between the date of the end of primary treatment until the institution of the next unplanned chemotherapy in randomized population.

    Measured: 36 months

  4. Progression Free Survival from enrolment (ePFS)

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

    Measured: 42 months

  5. Overall Survival from enrolment (eOS)

    OS will be defined as the time between the date of enrolment and the date of death from any cause

    Measured: 42 months

  6. Complete Response (CR) Rate

    Proportion of CR according to the Cheson 2007 response criteria at the end of consolidation phase.

    Measured: At the end of the consolidation phase (6 months)

  7. Overall Response Rate (ORR)

    ORR at the end of the consolidation phase is defined as Complete Response (CR) or Partial Response according to the Cheson 2007 response criteria.

    Measured: At the end of the consolidation phase (6 months)

  8. Toxicity

    Incidence of grade 3 or higher Toxicity measured by CTCAE v.4.03 during therapy.

    Measured: 42 months

  9. Molecular Response rate (MR)

    Rate of MR will be defined as the proportion of patients achieving PCR negativity after the consolidation phase and during follow up.

    Measured: 36 months

  10. Molecular Response rate conversion (cMR)

    Rate of conversion will be defined as the proportion of patients with baseline PCR-positivity converting to PCR-negativity during treatment.

    Measured: 6 months

  11. Molecular Relapse Rate (MRR)

    Rate of molecular relapse will be defined as the proportion of patients with PCR-negativity after treatment converting to PCR-positivity during the first two years of follow-up.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Apr 2013 (estimated)
  2. Study startJan 2012
  3. Primary completionOct 2019
  4. Study completionJan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
159 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01827605
Sponsor's protocol ID
FIL_FLAZ-12
Status last verified
Dec 2023
First submitted
5 Apr 2013
Last updated
9 Sep 2026
Results posted
No
Data monitoring committee
No

Publications

  • Ladetto M, Tavarozzi R, Zanni M, Evangelista A, Ferrero S, Tucci A, Botto B, Bolis S, Volpetti S, Zilioli VR, Puccini B, Arcari A, Pavone V, Gaidano G, Corradini P, Tani M, Cavallo F, Milone G, Ghiggi C, Pinto A, Pastore D, Ferreri AJM, Latte G, Patti C, Re F, Benedetti F, Luminari S, Pennese E, Bossi E, Boccomini C, Anastasia A, Bottelli C, Ciccone G, Vitolo U. Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapsed/refractory follicular lymphoma: a Fondazione Italiana Linfomi multicenter, randomized, phase III trial. Ann Oncol. 2024 Jan;35(1):118-129. doi: 10.1016/j.annonc.2023.10.095. Epub 2023 Nov 3.

    PubMed 37922989

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ZEVALIN and BEAM in people with Relapsed Follicular Lymphoma, run by Fondazione Italiana Linfomi - ETS at 38 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival from randomization (rPFS) (time frame: 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01827605, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.

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