High tumor burden Follicular Lymphoma MedDRA version: 24.0 Level: LLT Classification code 10080213 Term: In situ follicular lymphoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: ENDOXAN BAXTER - 200 MG POLVERE PER SOLUZIONE INIETTABILE 10 FLACONI VETRO TIPO III 200 MG
Product Name: Ciclofosfamide
Product Code: [IMP4]
Pharmaceutical Form:
INN or Proposed INN: CICL
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Histologically documented diagnosis of CD20+ Follicular lymphoma grade 1-2 or 3a, according to WHO 2017; 2) Age = 18 years; 3) ECOG performance status 0-2; 4) No previous immunochemotherapy for the lymphoma (localized radiotherapy or rituximab monotherapy with max of 4 doses are allowed); 5) Ann Arbor stage II-IV; 6) High tumor burden as per GELF criteria; 7) 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); 8) Adequate hematological counts (unless due to bone marrow involvement by lymphoma); 9) Adequate renal function defined as creatinine = 2 mg/dL, unless secondary to lymphoma; 10) Adequate hepatic function defined as bilirubin = 2 mg/dL, unless secondary to lymphoma; 11) LVEF > 50% at bidimensional echocardiogram (mandatory only for patients receiving R/G-CHOP); 12) Life expectancy = 6 months; 13) Subject understands and voluntarily signs an informed consent form; 14) Subject must be able to adhere to the study visit schedule and other protocol requirements; 15) 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 301 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 301
Exclusion criteria
Exclusion criteria: 1) Histological diagnosis different from FL grade 1-3a WHO 2017 classification; 2) Suspect or clinical evidence of CNS involvement by lymphoma; 3) Contraindication to the use of anti-CD20 monoclonal antibodies; 4) 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; 5) 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; 6) 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; 7) 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 SARS-CoV-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; 8) Women who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that, in patients with newly diagnosed, advanced stage Follicular Lymphoma (FL) with high tumor burden according to the GELF criteria, a treatment strategy that reduces the number of chemotherapy cycles in case of early response to immunochemotherapy is not inferior compared to standard therapy at full dose in terms of progression-free survival (PFS).;Secondary Objective: •to compare the response rates and the rate of adverse events between the Standard and Experimental treatment; •to compare a shortened vs full dose program in terms QoL •to recognized patients’ characteristics/biomarkers for identifying patients suitable for shortened chemotherapy treatment; •to assess the role MRD and the role of cfDNA analysis in predicting patient outcome; •to assess whether cfDNA analysis could be used to monitor residual disease; •to correlate response and survival with clinical and biologic prognostic factors; •to assess long-term outcome of the patients; •to complement radiomics analysis to TMTV to correlate it to the prognosis and evaluate the correlation of TMTV/radiomics at baseline with response; •to compare Lugano classification and TMTV/radiomics analysis results obtained from PET studies reconstructed both with OSEM - w/wo PSF - and RR)algorithm.;Primary end point(s): Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: 104 months PFS will be measured from the time of study entry to documented progression or to the patient’s death as a result of any causes. Subjects with incomplete follow-up or with no disease evaluation will be censored at the date of last available documented status of freedom from failure. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Response rate (ORR) and Complete response rate (CCR); Molecular response evaluated by polymerase chain reaction (PCR) assessment of Bcl2/IgH rearrangement; Overall Survival (OS); Event-Free Survival (EFS); Safety of the treatment according to the current version of the CTCAE; Quality of life evaluated through the Patient reported outcomes (PROs) by means of the FACT-Lym questionnaire;Timepoint(s) of evaluation of this end point: 80 months ORR and CRR will be defined according to Response Criteria for NHL with PET (Lugano 2014). ORR will include the sum of CR+PR while CRR will include only CR: both of them will be evaluated on assessed patients and on all treated patients, considering patients without a response assessment (due to any reason) as non-responders. The best overall response will be defined as the best response between the date of beginning of therapy and the last restaging. Patients without response assessment (due to whatever reason) will be considered as non-responders.; 80 months Molecular response assessed by means of the evaluation of the Bcl2/IgH rearrangement at baseline and of the Minimal Residual Disease (MRD) at subsequent defined timepoints; 104 months OS will be measured from the time o | — |
Countries
Italy
Contacts
Public ContactUffici studi FIL
Fondazione Italiana Linfomi ONLUS
Outcome results
None listed