Primary Central Nervous System Lymphoma Clinical Trial
— FIORELLAOfficial title:
Randomized Phase II Trial on Fitness- and Comorbidity- Tailored Treatment in Elderly Patients With Newly Diagnosed Primary CNS Lymphoma (FIORELLA Trial)
Primary central nervous system lymphomas are rare aggressive malignancies, usually treated in two steps: an induction phase (where a combination of chemotherapy is given) followed by a consolidation phase (where patients usually receive one of the following: whole-brain irradiation, chemotherapy supported by autologous stem-cell transplantation, other type of chemotherapy, or are just observed). The feasibility of this overall strategy, for several reasons, is limited in elderly patients . This study involves patients aged ≥70 years. The more fit patients will receive the standard chemotherapy combination (high-dose methotrexate, procarbazine and rituximab) as induction. Responding patients will receive either procarbazine or lenalidomide as maintenance therapy; the aim is to evaluate the efficacy of these two drugs. The more fragile patients will receive a less aggressive therapy consisting of concomitant whole-brain radiotherapy, temozolomide and rituximab as induction therapy, followed by temozolomide as maintenance treatment; the aim is to evaluate the efficacy of this combination of treatment.
Status | Recruiting |
Enrollment | 208 |
Est. completion date | October 31, 2023 |
Est. primary completion date | October 31, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 70 Years and older |
Eligibility | Inclusion Criteria: - Histologically or cytologically assessed diagnosis of CD20+ diffuse large B-cell lymphoma. - Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy. - Lymphoma exclusively localized in the central nervous system (brain parenchyma and/or meningeal/CSF dissemination and/or eyes and/or cranial nerves). - Previously untreated patients (previous or ongoing steroid therapy admitted). - Age =70 years - Patients not eligible for high-dose chemotherapy supported by autologous stem cell transplant - ECOG PS =3. - Adequate bone marrow, cardiac, renal, and hepatic function - No previous or concurrent malignancies with the exception of surgically cured carcinoma in-situ of the cervix, carcinoma of the skin or other cancers without evidence of disease at least for 3 years (patients with a previous lymphoma at any time are NOT eligible). - Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. - No concurrent treatment with other experimental drugs. - Patients receiving oral lenalidomide or procarbazine must agree to avoid sharing the study medication with another person and to return all unused study drug to the investigator. - Male patients must agree to always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking lenalidomide, during dose interruptions and for up to 7 days after treatment discontinuation, even if they have undergone a successful vasectomy. - Informed consent from the patient, or legal representative, obtained before registration. Exclusion Criteria: - Lymphoma entity other than diffuse large B-cell lymphoma. - Extra-CNS disease. - Lymphoma exclusively localized in the eyes - Lymphoma infiltration of the cranial nerves as exclusive site of disease - Previous antineoplastic treatment for the PCNSL. - Patients eligible for ASCT. - HBsAg- and HCV-positive patients; HBsAg- and HCV-positive patients. HBcAb+ is not exclusion criteria in the absence of detectable levels HBVDNA. - HIV disease or immunodeficiency. - Severe concomitant illnesses/medical conditions (e.g. impaired respiratory and/or cardiac function, uncontrolled diabetes mellitus despite optimal medical management). - Active infectious disease. - Hypersensitivity to any active principle and/or any excipient according to the contraindications reported in the Summary of Product Characteristics (SmPCs) of the anticancer drugs used in the study |
Country | Name | City | State |
---|---|---|---|
Denmark | Aarhus University Hospital | Aarhus | |
Denmark | Odense University Hospital | Odense | |
Finland | Oulu University Hospital | Oulu | |
Finland | Tampere University Hospital | Tampere | |
Israel | Tel Aviv Sourasky Medical Center | Tel Aviv | |
Italy | Ospedale C.e G. Mazzoni | Ascoli Piceno | |
Italy | Centro di Riferimento Oncologico | Aviano | (pn) |
Italy | Bari IRCCS Istituto Tumori | Bari | |
Italy | ASST Spedali Civili di Brescia | Brescia | |
Italy | Ospedale Antonio Perrino | Brindisi | |
Italy | Azienda Ospedaliera Universitaria (AOU) Careggi | Firenze | |
Italy | Meldola, IRST - ISTITUTO SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI TUMORI | Meldola | |
Italy | Milano - Îstituto Besta | Milan | |
Italy | Milano Niguarda | Milan | |
Italy | Milano, IRCCS Ospedale San Raffaele | Milan | |
Italy | Modena, Policlinico Universitario | Modena | |
Italy | ASST Monza - Ospedale S. Gerardo | Monza | |
Italy | Pescara, Presidio Ospedaliero UOS dipartimentale centro di diagnosi e terapia Linfomi | Pescara | |
Italy | Piacenza | Piacenza | |
Italy | Ravenna - Ospedale di Ravenna - IRST | Ravenna | |
Italy | Reggio Emilia - Arcispedale Santa Maria Nuova - IRCCS | Reggio Emilia | |
Italy | AUSL della Romagna - Presidio Ospedaliero Rimini - Ospedale "Infermi" | Rimini | |
Italy | Policlinico Umberto I - Università La Sapienza | Roma | |
Italy | Roma - Unicampus-Bio | Roma | |
Italy | S. Giovanni Rotondo - Casa Sollievo della sofferenza | San Giovanni Rotondo | |
Italy | Siena - Azienda Ospedaliera Universitaria Senese | Siena | |
Italy | Terni - Ospedale di Terni | Terni | |
Italy | Torino neurooncologia - AOU CITTA' DELLA SALUTE E DELLA SCIENZA DI TORINO | Torino | |
Italy | Tricase - Ospedale "Card. G. Panico" | Tricase | |
Italy | Udine, Azienda Ospedaliera Universitaria | Udine | |
Switzerland | Basel - Universitätsspital | Basel | |
Switzerland | IOSI - Oncology Institute of Southern Switzerland | Bellinzona | |
Switzerland | Bern - Inselspital | Bern | |
Switzerland | St. Gallen - Kantonsspital | Saint Gallen | |
Switzerland | Universitätsspital Zürich | Zürich |
Lead Sponsor | Collaborator |
---|---|
International Extranodal Lymphoma Study Group (IELSG) |
Denmark, Finland, Israel, Italy, Switzerland,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Two years Progression Free Survival (PFS) - part A | The primary objective is to evaluate whether lenalidomide administered as maintenance treatment after achievement of disease stabilization or better response by standard induction therapy results in a higher 2-year PFS rate as compared to procarbazine maintenance. The corresponding primary endpoint is the difference in 2-years PFS between the two treatment arms. |
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years. | |
Primary | Two years Progression Free Survival (PFS) - part B | From date of maintenance start until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years | ||
Secondary | Duration of response (part A) | Difference between the two arms in time from first assessment of response (PR or CR) to relapse/progression | From date of first assessment of response (PR or CR) until the date of first documented progression, assessed up to 2 years from randomization. | |
Secondary | Response Rates (part B) | Proportion of patients showing CR, PR, SD, PD as best response to treatment | From the start of the treatment until disease progression, assessed up to 2 years from start of maintenance. | |
Secondary | Overall survival (OS) | From date of induction treatment start until the date of death from any cause or the date of the last visit in patients still alive at study end, assessed up to 2 years from start of maintenance. | ||
Secondary | Relapse rates and patterns | Analysis of the following relapse rates and patterns: primary site vs. secondary CNS sites vs. extra-CNS sites; CNS sites: brain, meninges, cranial nerves, and/or eyes | From the start of the treatment until disease progression, assessed up to 2 years from start of maintenance. | |
Secondary | Incidence of Treatment-Emergent Adverse Events | Analysis of adverse events and adverse reactions incidence and severity | From the 2 weeks preceding treatment start through study completion, an average of 2.5 years | |
Secondary | Early and late neurotoxicity | Analysis of incidence and severity of early and late neurotoxicity assessed by specific neuropsychological and quality of life tests up to 2 years from maintenance treatment start | From maintenance up to 2 years. |
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