Clinical trial • Phase III • Oncology|Haematology

OBINUTUZUMAB for Follicular lymphoma|Follicular B-cell non-Hodgkin's lymphoma

Phase III trial of OBINUTUZUMAB for Follicular lymphoma|Follicular B-cell non-Hodgkin's lymphoma.

Overview

Trial Therapeutic Area
Oncology|Haematology
Trial Disease
Follicular lymphoma|Follicular B-cell non-Hodgkin's lymphoma
Trial Stage
Phase III
Drug Modality
Small molecule|Monoclonal antibody
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
06-11-2024
First CTIS Authorization Date
27-11-2024

Trial design

Randomised, open-label, comparator agents listed in the application: prednisone (max daily dose 40 mg/m2, oral), cyclophosphamide (max daily dose 750 mg/m2, iv), bendamustine (max daily dose 90 mg/m2, iv), vincristine (max daily dose 2 mg, iv), rituximab (intravenous formulation max daily dose 375 mg/m2; subcutaneous formulation max daily dose 1400 mg), doxorubicin (max daily dose 50 mg/m2, iv), obinutuzumab (max daily dose 1000 mg, iv). schedule details not specified in the record.-controlled Phase III trial in Italy.

Randomised
Yes
Open Label
Yes
Comparator
Comparator agents listed in the application: PREDNISONE (max daily dose 40 mg/m2, oral), CYCLOPHOSPHAMIDE (max daily dose 750 mg/m2, IV), BENDAMUSTINE (max daily dose 90 mg/m2, IV), VINCRISTINE (max daily dose 2 mg, IV), RITUXIMAB (intravenous formulation max daily dose 375 mg/m2; subcutaneous formulation max daily dose 1400 mg), DOXORUBICIN (max daily dose 50 mg/m2, IV), OBINUTUZUMAB (max daily dose 1000 mg, IV). Schedule details not specified in the record.
Target Sample Size
602

Eligibility

Recruits 602 No vulnerable populations selected (isVulnerablePopulationSelected: false). Inclusion criteria require that the subject "understands and voluntarily signs an informed consent form approved by the National Ethics Committee (NEC) prior to the initiation of any screening or study-specific procedures;" Age inclusion is ≥ 18 years. Separate informed consent documents listed for patient, biological study, privacy and pregnancy indicate specific consent handling; no minors or assent procedures are described..

Pregnancy Exclusion
Women who are pregnant or breastfeeding.
Vulnerable Population
No vulnerable populations selected (isVulnerablePopulationSelected: false). Inclusion criteria require that the subject "understands and voluntarily signs an informed consent form approved by the National Ethics Committee (NEC) prior to the initiation of any screening or study-specific procedures;" Age inclusion is ≥ 18 years. Separate informed consent documents listed for patient, biological study, privacy and pregnancy indicate specific consent handling; no minors or assent procedures are described.

Inclusion criteria

  • {"criterion_text":"- Histologically documented diagnosis of grade 1-2 or 3a follicular lymphona or classic follicular lymphoma, as defined in the 4 th and 5 th editions of the World Health Organization (WHO) classification respectively;\n- Adequate hepatic function defined as bilirubin ≤ 2 mg/dL, unless secondary to lymphoma or Gilbert syndrome\n- LVEF > 50% at bidimensional echocardiogram (mandatory only for patients receiving R/G-CHOP);\n- Life expectancy ≥ 6 months;\n- Subject understands and voluntarily signs an informed consent form approved by the National Ethics Committee (NEC) prior to the initiation of any screening or study-specific procedures;\n- Subject must be able to adhere to the study visit schedule and other protocol requirements\n- Women of childbearing potential (WOCBP) and men must agree to use effective contraception if sexually active. This applies for the time period between signing of the informed consent form and 12 months after last rituximab dose or 18 months after last obinutuzumab dose. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control (failure rate of less than 1%) e.g., intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner. The use of condoms by male patients is required (even if surgically sterilized, i.e., status post vasectomy) unless the female partner is permanently sterile. Full sexual abstinence is admitted when this is in line with the preferred and usual lifestyle of the subject, for the same time period planned for other methods of birth control (see above). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner) and withdrawal are not acceptable methods of contraception)\n- Age ≥ 18 years\n- ECOG performance status 0-2\n- No previous immunochemotherapy for the lymphoma (localized radiotherapy or rituximab monotherapy with max of 4 doses are allowed);\n- Ann Arbor stage II-IV\n- High tumor burden as per GELF criteria defined as the presence of at least one of the following: - systemic symptoms; - Tumor bulk (any nodal or extranodal tumor mass with diameter > 7 cm); - involvement of ≥ 3 nodal sites, each with a diameter ≥ 3 cm; - splenomegaly; - compressive syndrome (organ compression); - serous effusion; - circulant malignant cells; - cytopenia; - ECOG-PS > 1; - LDH > upper limit of normality (ULN); - β2-microglobulin > 3 mg/L. In the absence of at least one of the GELF criteria, the presence of extranodal disease applies provided that the bone marrow is not the only extranodal site\n- At least one site of measurable nodal disease at baseline ≥ 1.5 cm in the longest transverse diameter as determined by CT scan (MRI is allowed if CT scan cannot be performed); or evaluable disease at baseline FDG-PET scan (at least one metabolic active site of disease)\n- Adequate hematological counts (unless due to bone marrow involvement by lymphoma) defined as follows: a. Absolute Neutrophil count (ANC) > 1.5 x 109 /L; b. Platelet count ≥ 80 x 109 /L ; c. Hemoglobin ≥ 10 g/dL\n- Adequate renal function defined as creatinine ≤ 2 mg/dL, unless secondary to lymphoma;"}

Exclusion criteria

  • {"criterion_text":"- Histological diagnosis different from grade 1-3a or cFL, as defined in the WHO classification (4 th and 5 th editions);\n- Suspect or clinical evidence of CNS involvement by lymphoma;\n- Contraindication to the use of anti-CD20 monoclonal antibodies;\n- Subject has received any anticancer therapy (chemotherapy, immunotherapy, investigational therapy, including targeted small molecule agents) within 14 days prior to the first dose of study drug;\n- Noteworthy history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent;\n- Any history of other active malignancies within 3 years prior to study entry, with the exception of: adequately treated in situ carcinoma of the cervix uterine; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; limited stage surgically removed breast cancer or adequately treated with radiation therapy; limited stage prostate carcinoma surgically removed or adequately treated with radiation therapy; previous malignancy confined and surgically resected with curative intent;\n- Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: - Uncontrolled and/or active systemic infection (viral, bacterial or fungal), including active ongoing infection from SARSCoV-2; - Chronic or acute hepatitis B (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e., HBsAg negative, HBsAb positive and HBcAb negative) or positive HBcAb from previous infection or intravenous immunoglobulins (IVIG) may participate; inactive carriers (HBsAg positive with undetectable HBV- DNA) are eligible. Patients with presence of HCV antibody are eligible only if PCR negative for HCV-RNA\n- HIV seropositivity;\n- Women who are pregnant or breastfeeding."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Progression-free survival (PFS).","definition_or_measurement_approach":"Not specified in the record beyond naming PFS as the primary endpoint."}

Secondary endpoints

  • {"endpoint_text":"- Overall Survival (OS);","definition_or_measurement_approach":"Overall survival (OS) — standard definition (time from randomization to death) is implied but not explicitly defined in the record."}
  • {"endpoint_text":"- Event Free Survival (EFS)","definition_or_measurement_approach":"Event Free Survival (EFS) — definition not explicitly provided in the record."}
  • {"endpoint_text":"- Response rate (overall [ORR] and complete [CRR], according to Cheson 2014);","definition_or_measurement_approach":"Response rates assessed according to Cheson 2014 criteria (as stated)."}
  • {"endpoint_text":"- Molecular response evaluated by polymerase chain reaction (PCR) assessment of Bcl2/IgH rearrangement;","definition_or_measurement_approach":"Molecular response measured by PCR assessment of Bcl2/IgH rearrangement (method stated)."}
  • {"endpoint_text":"- Safety of the treatment according to the current version of the CTCAE","definition_or_measurement_approach":"Safety evaluated per current CTCAE (Common Terminology Criteria for Adverse Events) version (as stated)."}
  • {"endpoint_text":"- Quality of life evaluated through the Patient reported outcomes (PROs) by means of the FACT-Lym questionnaire","definition_or_measurement_approach":"Quality of life assessed using the FACT-Lym PRO questionnaire (as stated)."}

Recruitment

Planned Sample Size
602
Recruitment Window Months
103
Consent Approach
Adults (Age ≥ 18) must "understand and voluntarily sign an informed consent form approved by the National Ethics Committee (NEC) prior to the initiation of any screening or study-specific procedures." Multiple subject information and consent documents are listed (patient consent form; patient information sheet; letter to GP; patient consent form for biological study; privacy information and consent forms including a pregnancy privacy/consent form). No assent procedures or minor/guardian consent are described; consent documents and recruitment materials are provided as separate documents in the application.

Geography

Total Number Of Sites
54
Total Number Of Participants
602

Italy

Earliest CTIS Part Ii Submission Date
10-10-2024
Latest Decision Or Authorization Date
24-03-2026
Processing Time Days
530
Number Of Sites
54
Number Of Participants
602

Sites

Site Name
Ospedale Di Sassuolo S.p.A.
Department Name
Day Hospital Oncologico
Contact Person Name
Sara Bigliardi
Contact Person Email
s.bigliardi@ausl.mo.it
Site Name
Azienda Sanitaria Locale Di Pescara
Department Name
UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi
Contact Person Name
Giuseppina Ricciuti
Contact Person Email
giuseppina.ricciuti@asl.pe.it
Site Name
Azienda Ospedaliero Universitaria Delle Marche
Department Name
Clinica di Ematologia
Contact Person Name
Silvia Trappolini
Site Name
Azienda Ospedaliera Universitaria di Ferrara
Department Name
Ematologia e fisiopatologia della coagulazione
Contact Person Name
Antonio Cuneo
Contact Person Email
cut@unife.it
Site Name
Istituto Oncologico Veneto
Department Name
SC Ematologia
Contact Person Name
Nilla Maschio
Contact Person Email
nilla.maschio@iov.veneto.it
Site Name
Azienda Unita Sanitaria Locale Di Piacenza
Department Name
U.O. Ematologia
Contact Person Name
Annalisa Arcari
Contact Person Email
a.arcari@ausl.pc.it
Site Name
Careggi University Hospital
Department Name
Unità funzionale di Ematologia
Contact Person Name
Benedetta Puccini
Site Name
Azienda Sanitaria Universitaria Giuliano Isontina
Department Name
SC Ematologia
Contact Person Name
Francesco Zaja
Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione
Contact Person Name
Ilaria Del Giudice
Contact Person Email
ilaria.delgiudice@uniroma1.it
Site Name
AORN San Giuseppe Moscati Avellino
Department Name
S.C. Ematologia e Trapianto emopoietico
Contact Person Name
Sonya De Lorenzo
Contact Person Email
sonya.delorenzo@tin.it
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
SC Ematologia
Contact Person Name
Carola Boccomini
Site Name
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Department Name
SCDU Ematologia
Contact Person Name
Gloria Margiotta
Contact Person Email
gloria.margiotta@med.uniupo.it
Site Name
Azienda Ospedaliera Regionale San Carlo
Department Name
U.O. Ematologia
Contact Person Name
Michele Cimminiello
Contact Person Email
miki-doc@virgilio.it
Site Name
Azienda Sanitaria Territoriale Di Ascoli Piceno
Department Name
UOC Ematologia
Contact Person Name
Piero Galieni
Contact Person Email
piero.galieni@sanita.marche.it
Site Name
Azienda Socio Sanitaria Territoriale Ovest Milanese
Department Name
U.O.C. Ematologia
Contact Person Name
Silvia Franceschetti
Site Name
Azienda Ospedaliero Universitaria Pisana
Department Name
U.O. Ematologia
Contact Person Name
Sara Galimberti
Contact Person Email
sara.galimberti@med.unipi.it
Site Name
Azienda Ospedaliera di Padova
Department Name
Ematologia
Contact Person Name
Francesco Piazza
Contact Person Email
francesco.piazza@unipd.it
Site Name
Azienda USL Toscana Centro
Department Name
SOS Oncoematologia
Contact Person Name
Simone Santini
Site Name
Azienda Sanitaria Locale Della Provincia Di Biella
Department Name
SSD Ematologia
Contact Person Name
Annarita Conconi
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
Ematologia
Contact Person Name
Silviaanna Bolis
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
Ematologia
Contact Person Name
Monica Tani
Contact Person Email
monica.tani@auslromagna.it
Site Name
Azienda Sanitaria Locale Br
Department Name
U.O. Ematologia e Trapianti di Midollo
Contact Person Name
Domenico Pastore
Contact Person Email
domenico.pastore0@gmail.com
Site Name
Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
Department Name
U.O. Ematologia con Trapianto
Contact Person Name
Pellegrino Musto
Contact Person Email
pellegrino.musto@uniba.it
Site Name
Istituto Di Candiolo Fondazione Del Piemonte Per L'Oncologia IRCCS
Department Name
Ematologia
Contact Person Name
Delia Rota Scalabrini
Contact Person Email
delia.rotascalabrini@ircc.it
Site Name
Azienda Ospedaliera Papardo
Department Name
S.C. Ematologia
Contact Person Name
Donato Mannina
Contact Person Email
donamanni@gmail.com
Site Name
ASL di Salerno - PO A. Tortora
Department Name
U.O. Onco-ematologia
Contact Person Name
Catello Califano
Contact Person Email
c.califano@aslsalerno.it
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
U.O. di Ematologia
Contact Person Name
Anna Merli
Contact Person Email
anna.merli@auslromagna.it
Site Name
Istituto Oncologico Veneto
Department Name
Oncologia 1
Contact Person Name
Dario Marino
Contact Person Email
dario.marino@iov.veneto.it
Site Name
Azienda Unita' Locale Socio Sanitaria N. 2 Marca Trevigiana
Department Name
S.C di Ematologia
Contact Person Name
Elisabetta Scarpa
Site Name
Azienda Ospedaliera Santa Croce E Carle
Department Name
S.C. di Ematologia e Trapianto di Midollo
Contact Person Name
Claudia Castellino
Contact Person Email
castellino.c@ospedale.cuneo.it
Site Name
Azienda Ospedaliera S Maria Di Terni
Department Name
SC Oncoematologia
Contact Person Name
Arcangelo Liso
Contact Person Email
arcangelo.liso@unipg.it
Site Name
Azienda Ospedaliera Universitaria San Giovanni Di Dio E Ruggi d'Aragona
Department Name
U.O. Ematologia
Contact Person Name
Carmine Selleri
Contact Person Email
cselleri@unisa.it
Site Name
Azienda Socio Sanitaria Territoriale Della Valtellina E Dell Alto Lario
Department Name
Medicina Interna
Contact Person Name
Andrea Maria Soccodato
Contact Person Email
andresocco@alice.it
Site Name
Azienda Ulss n.3 Serenissima – Ospedale di Mirano
Department Name
UOC di Oncologia ed Ematologia Oncologica
Contact Person Name
Claudia Minotto
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Ematologia
Contact Person Name
Stefan Hohaus
Contact Person Email
stefan.hohaus@Unicatt.it
Site Name
Azienda Ospedaliera Universitaria Senese
Department Name
U.O.C. Ematologia
Contact Person Name
Emanuele Cencini
Contact Person Email
cencioema@libero.it
Site Name
Azienda Sanitaria Locale Roma 2
Department Name
UOC Ematologia
Contact Person Name
Elisabetta Abruzzese
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
Ematologia
Contact Person Name
Michele Merli
Site Name
Azienda Unita Locale Socio Sanitaria N. 1 Dolomiti
Department Name
UOC Oncologia
Contact Person Name
Fable Zustovich
Site Name
Azienda Ospedaliero-Universitaria Ss.Antonio E Biagio E C.Arrigo Alessandria
Department Name
SCDU Ematologia
Contact Person Name
Manuela Zanni
Contact Person Email
manuela.zanni@ospedale.al.it
Site Name
Centro Di Riferimento Oncologico Di Aviano
Department Name
Divisione di Oncologia e dei Tumori immuno-correlati
Contact Person Name
Michele Spina
Contact Person Email
mspina@cro.it
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
Ematologia
Contact Person Name
Chiara Ghiggi
Contact Person Email
chiara.ghiggi@hsanmartino.it
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Ematologia
Contact Person Name
Francesco Malaspina
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
Ematologia
Contact Person Name
Federica Cavallo
Contact Person Email
f.cavallo@unito.it
Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
SC Ematologia
Contact Person Name
Vittorio Ruggero Zilioli
Site Name
Azienda Socio Sanitaria Territoriale Della Valle Olona
Department Name
S.C. Ematologia
Contact Person Name
Elisabetta Todisco
Site Name
Azienda USL IRCCS Di Reggio Emilia
Department Name
Ematologia
Contact Person Name
Stefano Luminari
Contact Person Email
stefano.luminari@ausl.re.it
Site Name
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Department Name
U.O. Ematologia
Contact Person Name
Salvatrice Mancuso
Contact Person Email
salvatrice.mancuso@unipa.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
Unità Linfomi - Dipartimento Oncoematologia
Contact Person Name
Andrés Ferreri
Contact Person Email
andres.ferreri@hsr.it
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
Div. di Ematologia
Contact Person Name
Luca Arcaini
Contact Person Email
luca.arcaini@unipv.it
Site Name
Azienda USL Toscana Centro
Department Name
SOS Ematologia clinica e oncoematologia
Contact Person Name
Sabrina Moretti
Site Name
Azienda Ospedaliero Universitaria Parma
Department Name
UO Ematologia e CTMO
Contact Person Name
Caterina Plenteda
Contact Person Email
cplenteda@ao.pr.it
Site Name
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
Department Name
Ematologia
Contact Person Name
Francesco Di Raimondo
Contact Person Email
diraimon@unict.it
Site Name
Azienda Socio Sanitaria Territoriale Santi Paolo E Carlo
Department Name
Oncoematologia
Contact Person Name
Vittorio Montefusco

Sponsor

Primary sponsor

Full Name
Fondazione Italiana Linfomi Ets
Organisation Type
Patient organisation/association
Country Of Registered Address
Italy

Investigational products

Investigational Product Name
OBINUTUZUMAB
Active Substance
OBINUTUZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Orphan Designation
Yes
Maximum Dose
1000 mg
Investigational Product Name
RITUXIMAB (intravenous)
Active Substance
RITUXIMAB
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Orphan Designation
Yes
Maximum Dose
375 mg/m2
Investigational Product Name
RITUXIMAB (subcutaneous)
Active Substance
RITUXIMAB
Modality
Monoclonal antibody
Routes Of Administration
SUBCUTANEOUS
Route
SUBCUTANEOUS
Orphan Designation
Yes
Maximum Dose
1400 mg
Investigational Product Name
DOXORUBICIN
Active Substance
DOXORUBICIN HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Orphan Designation
Yes
Maximum Dose
50 mg/m2
Investigational Product Name
BENDAMUSTINE
Active Substance
BENDAMUSTINE HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Maximum Dose
90 mg/m2
Investigational Product Name
CYCLOPHOSPHAMIDE
Active Substance
CYCLOPHOSPHAMIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Maximum Dose
750 mg/m2
Investigational Product Name
VINCRISTINE
Active Substance
VINORELBINE / VINCRISTINE (product name VINCRISTINE, jsonActiveSubstanceNames: vinorelbine)
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Maximum Dose
2 mg
Investigational Product Name
PREDNISONE / PREDNISOLONE
Active Substance
PREDNISOLONE / PREDNISONE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Maximum Dose
40 mg/m2
Combination Treatment
Yes

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