Study to Evaluate the Efficacy of Response-adapted Strategy in Follicular Lymphoma
Conditions
Follicular Non-Hodgkin's Lymphoma
Conditions: official terms
Lymphoma - Lymphoma, Follicular - Lymphoma, Non-Hodgkin
Study Type
Interventional
Study Phase
Phase 3
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: R-CHOP Type: Drug
Name: Observation Type: Drug
Name: Maintenance weekly x4 Type: Drug
Name: Ibritumomab Tiuxetan + Maintenance Type: Drug
Name: Standard Maintenance Type: Drug
Overall Status
Recruiting
Summary
Recently, the availability of R has substantially changed therapeutic approach to FL patients, since its combination with chemotherapy has improved response rates, progression free survival (PFS) and overall survival (OS). Based on the results of recently completed randomized studies the standard treatment for patients with FL should consist of an initial therapy with R-CHOP combination followed by two-year maintenance with R. Although results of randomized trials confirmed that this approach results in an improved patients' outcome and made a step forward in the management of patients with FL, one important question that can be raised is if this approach is really needed for all patients with FL or if some of them could benefit from a reduced intensity treatment achieving the same results in terms of outcome and survival . This question is of particular interest for newly diagnosed patients for whom maintenance does not affect OS.

More recent data demonstrated that the outcome of patients with FL can be further predicted by evaluating the quality of response to therapy studying minimal residual disease (MRD). This project addresses the objective of evaluating if combining clinical response assessed on FDG-PET scan and molecular response measured through MRD detection could permit to single out groups of patients at different risk of progression and to consequently modulate maintenance therapies, with the aim to provide clinicians a more rational use of the available diagnostic and therapeutic resources.
Detailed Description
This is a multicenter, randomized, phase III, superiority study comparing standard vs response driven approach to maintenance. Adult patients (age ≥ 18 years) with naïve, untreated follicular lymphoma, stage II-IV, Follicular Lymphoma International Prognostic Index 2 (FLIPI2) >0 requiring a therapeutic intervention will be recruited and randomly assigned in a 1:1 ratio to either standard or experimental arm.

All patients will receive the same induction therapy with 6 cycles of R-CHOP and 2 additional doses of Rituximab.

At baseline patients will be assessed for molecular status and staged by means of CT scan. A baselineFluorine-18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) scan should also be performed.

At the end of chemoimmunotherapy all patients will be assessed for disease response by common clinical and laboratory examination, CT scan and FDG-PET. An intermediate assessment of response with CT scan and FDG-PET will also be performed after the first four courses of R-CHOP.

At the end of induction therapy the status of minimal residual disease will be also evaluated.

After induction treatment all responding patients in the standard arm will receive standard maintenance therapy with Rituximab (every 2 months for 2 years), while patients in the experimental arm will be subdivided into two risk groups and assigned to different post induction treatments based on FDG-PET and MRD results. In both arms, patients with stable or progressive disease (PET positive and less than PR on CT scan) will be addressed to salvage treatment chosen at physician discretion.

In the experimental arm, risk group allocation will be performed primarily on the basis of FDG-PET results:

- Group 1 (low risk): negative FDG-PET

- Group 2 (high risk): positive FDG-PET

Patients at low risk (FDG-PET negative) will received maintenance therapy according to their MRD status,particularly:

- Group 1a (MRD negative): observation

- Group 1b (MRD positive): pre-emptive Rituximab therapy

Patient at high risk (FDG-PET positive) will receive maintenance regardless of their MRD status:

· Group 2: intensified maintenance ((90)Y Ibritumomab Tiuxetan + Rituximab maintenance )
Criteria for eligibility
Healthy Volunteers: Accepts Healthy Volunteers
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Histological diagnosis of B-Cell CD20+ Follicular Lymphoma (FL), grade I, II, IIIa according to the WHO 2008 classification

- ECOG performance status 0-2

- Age ≥ 18 years

- Ann Arbor stage II-IV

- FLIPI2>0

- Presence of evaluable/measurable disease after diagnostic biopsy

- At least one of the following criteria for defining active disease:

- systemic symptoms

- cytopenia due to bone marrow involvement

- LDH> upper normal value

- any nodal or extranodal tumor mass with a diameter >7cm

- involvement of ≥ 3 nodal sites, each with a diameter of ≥ 3cm

- extranodal disease

- rapidly progressive disease

- Life expectancy > 6 months

- Left ventricular ejection fraction (LVEF) ³ 50%

- Serum negativity for HIV

- Serum negativity for HBsAg; HBcAb positive but HBV-DNA negative patients are allowed with mandatory Lamivudine prophylaxis.

- Serum negativity for HCV, except for those patients without signs of active viral replication assessed by HCV-RNA copies

- Serum creatinine < 2mg/dl , serum bilirubin < 1.5mg/dl, aspartate amino-transferase (AST/GOT) £ 2.5xUNV, alanine amino-transferase (ALT/GPT) £ 2.5xUNV, and alkaline phosphatase £ 4 times the upper limit of normal (unless the increase is attributed directly to the presence of tumour by the Investigator)

- Patients with no previous treatment for the lymphoma with the exception of locoregional radiotherapy (IFRT)

- Adequate measure adoption to avoid pregnancy

- Written informed consent given at time of registration

- Patient must be accessible for treatment and follow up.

Exclusion Criteria:

- Histological diagnosis of :

- any lymphoma other than follicular lymphoma and all CD20 negative B-cell lymphomas

- grade III b follicular lymphoma

- evidence of transformation to high grade lymphoma

- Ann Arbor stage I

- Suspect or clinical evidence of CNS involvement by lymphoma

- History of other malignancies within 5 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer, low grade, early stage localized prostate cancer treated surgically with curative intent, good prognosis DCIS of the breast treated with lumpectomy alone with curative intent

- Evidence of any severe active acute or chronic infection

- Concurrent co-morbid medical condition which might exclude administration of full dose chemotherapy

- Severe chronic obstructive pulmonary disease with hypoxemia

- Severe diabetes mellitus difficult to control with adequate insulin therapy

- Myocardial infarction within 6 months before study entry

- Clinically significant secondary cardiovascular disease e.g. uncontrolled hypertension, (resting diastolic blood pressure >115 mmHg), uncontrolled multifocal cardiac arrhythmias, symptomatic angina pectoris or congestive cardiac failure NYHA class III-IV

- HbsAg-positive, HIV-positive, or HCVAb-positive patients

- Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins

- Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

- Follicular lymphoma, showing a negative baseline PET scan.
Locations
Ospedale S. Nicola Pellegrino Di Trani
Trani, Barletta, Italy
Status: Recruiting
Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Sede Di Meldola (Fc)
Meldola, Forlì Cesena, Italy
Status: Recruiting
Irccs Istituto Clinico Humanitas
Rozzano, Milano, Italy
Status: Recruiting
Azienda Ospedaliera S. Gerardo Di Monza
Monza, Monza Brianza, Italy
Status: Recruiting
Azienda Ospedaliera "S. Maria"
Terni, Perugia, Italy
Status: Recruiting
Irccs Centro Di Riferimento Oncologico (Cro)
Aviano, Pordenone, Italy
Status: Recruiting
Irccs Centro Di Riferimento Oncologico Di Basilicata (Crob)
Rionero in Vulture, Potenza, Italy
Status: Recruiting
P.O. Umberto I
Nocera Inferiore, Salerno, Italy
Status: Recruiting
Fondazione Del Piemonte Per L'Oncologia Ircc Di Candiolo
Candiolo, Torino, Italy
Status: Recruiting
Ospedale Civile Ss. Antonio E Biagio Di Alessandria - Alessandria (Al)
Alessandria, Italy
Status: Recruiting
A.O. Universitaria Ospedali Riuniti - Ospedale Umberto I Di Ancona _
Ancona, Italy
Status: Recruiting
A.O. Universitaria Ospedale Consorziale Policlinico Di Bari
Bari, Italy
Status: Recruiting
Ospedali Riuniti - Bergamo -
Bergamo, Italy
Status: Recruiting
A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
Bologna, Italy
Status: Recruiting
Asp Di Bolzano - Comprensorio Sanitario Di Bolzano
Bolzano, Italy
Status: Recruiting
Pres.Ospedal.Spedali Civili Brescia
Brescia, Italy
Status: Recruiting
Stabilimento "Perrino" - Brindisi -
Brindisi, Italy
Status: Recruiting
Ospedale Armando Businco - Cagliari
Cagliari, Italy
Status: Recruiting
A.O. Universitaria Ospedale Vittorio Emanuele Di Catania
Catania, Italy
Status: Recruiting
Azienda Ospedaliera S. Croce E Carle Di Cuneo
Cuneo, Italy
Status: Recruiting
A.O. Universitaria Careggi Di Firenze
Firenze, Italy
Status: Recruiting
A.O. Universitaria S. Martino Di Genova
Genova, Italy
Status: Recruiting
A.O. Universitaria S. Martino Di Genova
Genova, Italy
Status: Recruiting
Presidio Ospedaliero - Matera -
Matera, Italy
Status: Recruiting
A.O. Universitaria Policlinico Martino Di Messina
Messina, Italy
Status: Recruiting
Azienda Ospedaliera Papardo
Messina, Italy
Status: Recruiting
Irccs Ospedale Maggiore Policlinico Di Milano
Milano, Italy
Status: Recruiting
Ospedale Ca` Granda-Niguarda
Milano, Italy
Status: Recruiting
A.O. Universitaria Policlinico Di Modena
Modena, Italy
Status: Recruiting
A.O. Universitaria Maggiore Della Carita' Di Novara
Novara, Italy
Status: Recruiting
Ospedale San Francesco
Nuoro, Italy
Status: Recruiting
A.O. "V. Cervello"
Palermo, Italy
Status: Recruiting
A.O. Universitaria Policlinico Giaccone Di Palermo
Palermo, Italy
Status: Recruiting
Azienda Ospedaliera Di Perugia - Ospedale S. Maria Della Misericordia -
Perugia, Italy
Status: Recruiting
Ospedale Civile Spirito Santo
Pescara, Italy
Status: Recruiting
Ausl Di Piacenza
Piacenza, Italy
Status: Recruiting
A.O. Universitaria Pisana
Pisa, Italy
Status: Recruiting
Ospedale Bianchi - Melacrino - Morelli
Reggio Calabria, Italy
Status: Recruiting
Ausl Di Rimini
Rimini, Italy
Status: Recruiting
Universita' Degli Studi Di Roma 'La Sapienza'
Roma, Italy
Status: Recruiting
A.O. Universitaria S. Giovanni Battista-Molinette Di Torino
Torino, Italy
Status: Recruiting
A.O. Universitaria S. Giovanni Battista-Molinette Di Torino
Torino, Italy
Status: Recruiting
Ospedale Di Trento - P.O. S.Chiara -
Trento, Italy
Status: Recruiting
A.O. Universitaria S. Maria Della Misericordia Di Udine
Udine, Italy
Status: Recruiting
Ospedale Di Circolo E Fondazione Macchi
Varese, Italy
Status: Recruiting
Start Date
July 2012
Completion Date
July 2019
Sponsors
Fondazione Italiana Linfomi ONLUS
Source
Fondazione Italiana Linfomi ONLUS
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page