VALEMETOSTAT TOSILATE for Relapsed/refractory B-cell lymphoma | Diffuse large B-cell lymphoma | Follicular lymphoma | Mantle cell lymphoma | Marginal zone lymphoma | Hodgkin lymphoma

Inclusion criteria

• {"criterion_text":"- 1.\tParticipants with confirmed histological diagnosis of aggressive B-cell lymphoma (diffuse large B-cell lymphoma-not otherwise specified, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma-not otherwise specified and high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rerrangement, transformed indolent lymphoma and grade 3b follicular lymphoma), FL (grade 1, 2, 3a), MCL, MZL or other indolent lymphoma (lymphoplasmacytic lymphoma), or HL according to the World Health Organization (WHO) 2016 classification of hematopoietic and lymphoid tissue"}
• {"criterion_text":"- 10.\tSufficient quantity of DNA available on the platform for EZH2 status determination (for aggressive B-cell lymphoma and FL)"}
• {"criterion_text":"- 11.\tSubjects with a history of hepatitis B or C are eligible on the condition that subjects have adequate liver function and are hepatitis B surface antigen negative and have undetectable serum HBV DNA and HCV RNA, respectively."}
• {"criterion_text":"- 12.\tFemales of childbearing potential must agree to use an highly effective birth control methods (defined in §13.6.1) during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 3 months after discontinuation of study treatment"}
• {"criterion_text":"- 13.\tMales with partners of childbearing potential must agree to use highly effective birth control methods during the study and 3 months after last treatment administration"}
• {"criterion_text":"- 14.\tMale and female participant ≥18 years of age at the time of informed consent"}
• {"criterion_text":"- 15.\tPatient covered by any social security system (France)"}
• {"criterion_text":"- 16.\tPatient who understands and speaks one of the country official language"}
• {"criterion_text":"- 17.\tParticipant who has provided written consent to participate in the study"}
• {"criterion_text":"- 2.\tParticipant who had progressive disease (PD) or did not have a response (CR or PR) in previous systemic therapy, or relapsed or progressed after previous systemic therapy"}
• {"criterion_text":"- 3.\tParticipant who has measurable disease by the Lugano criteria (ie longest diameter of a nodal site > 1.5cm and/or longest diameter of an extranodal site > 1.0 cm)"}
• {"criterion_text":"- 4.\tParticipant who had previous standard therapy with at least: (note: patients having received prior CAR-T therapy can be enrolled): -\tFor aggressive B-cell lymphoma: 2 prior lines of therapy (in transformed indolent lymphoma patient must have received at least one line of treatment containing an anthracycline-based regimen before or after transformation) containing an anti-CD20 antibody and an anthracycline (unless anthracycline-based therapy is contraindicated) and patient deemed ineligible for high-dose therapy and ASCT based on physician’s assessment or age ≥ 65 years or with a hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score ≥3. In the best interest of the patient, the treating physician must ensure CAR-T have been discussed among the treament options before considering enrollment in this study. -\tFor FL, MZL and other indolent NHL: 2 prior lines of systemic therapy with at least one anti-CD20 monoclonal antibody. Local involved field radiotherapy for limited stage disease is not considered as a previous line. Subjects with prior ASCT or CAR-T cells may be included. In the best interest of the patient, the treating physician must ensure CAR-T have been discussed among the treament options before considering enrollment in this study. Note: for Splenic Marginal Zone Lymphoma (SMZL), splenectomy is considered as one line; for Extranodal Marginal Zone Lymphoma (ENMZL), Helicobacter pylori eradication is not considered as a previous line; indolent (ie FL or MZL) relapse after aggressive B-cell lymphoma can be enrolled and prior treatment lines for the aggressive lymphoma are taken into account for inclusion criteria. -\tFor MCL: 2 prior lines including at least one immunochemotherapy and one BTK inhibitor. -\tFor HL: 3 prior lines including at least one line with anthracycline-based chemotherapy (unless anthracycline-based therapy is contraindicated), one line containing brentuximab-vedotin and one line containing an anti-PD1 or anti-PDL1 antibody and patient deemed ineligible for high-dose therapy and ASCT based on physician’s assessment or age ≥ 65 years or with a hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score ≥3"}
• {"criterion_text":"- 5.\tParticipant with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2"}
• {"criterion_text":"- 6.\tAdequate renal function defined as calculated creatinine clearance ≥ 40 mL/min per the Cockcroft and Gault formula"}
• {"criterion_text":"- 7.\tAdequate bone marrow function: -\tAbsolute neutrophil count (ANC) > 1000/mm3 (≥ 1 × 109/L) without growth factor support (G-CSF) for at least 7 days -\tPlatelets ≥ 75,000/mm3 (≥ 75 × 109/L /L) evaluated after at least 7 days since last platelet transfusion -\tHemoglobin > 8.0 g/dL evaluated after at least 7 days since last transfusion"}
• {"criterion_text":"- 8.\tAdequate liver function: -\tTotal bilirubin < 1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia due to Gilbert’s syndrome -\tAlkaline phosphatase (ALP) (in the absence of bone disease), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) < 3 × ULN (< 5 × ULN if subject has liver involvement due to lymphoma)"}
• {"criterion_text":"- 9.\tAdequate tissue (surgical excision is recommended) for central pathology review and biological caracterisation"}

Exclusion criteria

• {"criterion_text":"- 1.\tParticipant with prior exposure to EZH2 inhibitor"}
• {"criterion_text":"- 10.\tHistory of autologous or allogeneic HCT within 90 days prior to the first dose of study drug"}
• {"criterion_text":"- 11.\tPatients taking corticosteroids within 2 weeks prior to first administration of study drug, unless administered at a cumulated dose equivalent of prednisone to ≤ 10mg/ day (within these 2 weeks)."}
• {"criterion_text":"- 12.\tParticipant with significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia"}
• {"criterion_text":"- 13.\tSubjects with malignancies other than B cell lymphomas except subjects who have been disease-free for 2 years (subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible)."}
• {"criterion_text":"- 14.\tPositive serology of human immunodeficiency virus (HIV)"}
• {"criterion_text":"- 15.\tParticipant with prolongation of corrected QT interval using Fridericia's formula (QTcF) to > 470 milliseconds (msec) (obtained on average of 3 ECGs)"}
• {"criterion_text":"- 16.\tParticipant with venous thrombosis or pulmonary embolism not treated"}
• {"criterion_text":"- 17.\tParticipant with complications of hepatic cirrhosis, interstitial pneumonia, or pulmonary fibrosis"}
• {"criterion_text":"- 18.\tKnowing or suspected hypersensitivity to active substance or to any of the excipients"}
• {"criterion_text":"- 19.\tParticipant with active infection requiring systemic therapy"}
• {"criterion_text":"- 2.\tParticipant with active lymphomatous involvement of the central nervous system (CNS) at screening"}
• {"criterion_text":"- 20.\tWoman who are pregnant (positive serum pregnancy test at screening) or breastfeeding"}
• {"criterion_text":"- Participant who were deemed as inappropriate to participate in the study by the investigator or sub-investigator"}
• {"criterion_text":"- 3.\tAny prior treatment-related (ie, chemotherapy, immunotherapy, radiotherapy) clinically significant toxicities that have not resolved to ≤ Grade 1 per CTCAE version 5.0, or prior treatment-related toxicities that are clinically unstable and clinically significant at time of enrollment."}
• {"criterion_text":"- 4.\tMajor surgery within 4 weeks before the first dose of study drug."}
• {"criterion_text":"- 5.\tInability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the bioavailability of the drug"}
• {"criterion_text":"- Subjects currently taking medications that are known moderate or strong CYP3A inducers (refer to Appendix 7 for a list of example drugs) o\tIf currently used, these medications need to be discontinued at least 14 days prior to study drug administration; replacement by alternative medications that are not moderate or strong CYP3A inducers can be considered according to medical need"}
• {"criterion_text":"- 7.\tVaccinated with live, attenuated vaccines within 6 months of enrollment (except COVID vaccine)"}
• {"criterion_text":"- 8.\tUse of any standard or experimental anti-cancer drug therapy within 4 weeks or a minimum of 5 half lives of the drug, whatever the shortest prior to first administration of study drug,"}
• {"criterion_text":"- 9.\tHistory of CAR T-cells therapy within 30 days prior to the first dose of study drug"}

Primary endpoints

• {"endpoint_text":"- overall response rate (ORR) defined as the proportion of subjects achieving best overall response of partial response (PR) or complete response (CR) at any time, according to the Lugano 2014 classification (PET-CT–Based Response for FDG-avid lymphomas or CT-Based Response if not) and determined by investigator.","definition_or_measurement_approach":"Defined as the proportion of subjects achieving best overall response of partial response (PR) or complete response (CR) at any time, according to the Lugano 2014 classification (PET-CT–Based Response for FDG-avid lymphomas or CT-Based Response if not) and determined by investigator."}

Secondary endpoints

• {"endpoint_text":"-\tRate of complete response (CR)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tProgression-free survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tDuration of response (DOR)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tTime to response (TTR)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tSafety","definition_or_measurement_approach":""}

France

Earliest CTIS Part Ii Submission Date

12-08-2024

Latest Decision Or Authorization Date

15-12-2025

Processing Time Days

490

Number Of Sites

20

Number Of Participants

125

Belgium

Earliest CTIS Part Ii Submission Date

12-08-2024

Latest Decision Or Authorization Date

18-02-2025

Processing Time Days

190

Number Of Sites

4

Number Of Participants

15

Primary sponsor

Full Name

LYSARC

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France