A PHASE II OPEN-LABEL STUDY EVALUATING VALEMETOSTAT TOSYLATE AS A SINGLE AGENT IN PATIENTS WITH RELAPSE/REFRACTORY B-CELL LYMPHOMA

Phase 1

• Conditions: RELAPSE/REFRACTORY B-CELL LYMPHOMA; MedDRA version: 21.0Level: PTClassification code 10003902Term: B-cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10003903Term: B-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2020-005225-81-BE
• Lead Sponsor: YSARC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-04-23
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 141

Inclusion Criteria

1 Participants with confirmed histological diagnosis of aggressive Bcell 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 (Waldenström macroglobulinemia, lymphoplasmacytic lymphoma), or HL according to the World Health Organization (WHO)
2016 classification of hematopoietic and lymphoid tissue
2 Participant 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
3 Participant 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)
4 Participant who had previous standard therapy with at least:
(note: patients having received prior CAR-T therapy can be enrolled):
a For 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
b For 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
c For MCL: 2 prior lines including at least one immunochemotherapy
and one BTK inhibitor
d For HL: 3 prior lines including at least one line with anthracyclinebased 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 HCT-CI score =3
5 ECOG performance status of 0 to 2
6 Adequate renal function defined as calculated creatinine clearance = 40 mL/min per the Cockcroft and Gault formula
7 Adequate bone marrow function:
- ANC > 1000/mm3 (= 1 × 109/L) without G-CSF for at least 7 days
- Platelets = 75,000/mm3 (= 75 × 109/L /L) [...]
- Hemoglobin > 8.0 g/dL [...]
8. Adequate liver function:
- Total bilirubin < 1.5 × the ULN except for unconjugated
hyperbil

Exclusion Criteria

1.Participant with prior exposure to EZH2 inhibitor
2.Participant with active lymphomatous involvement of the central nervous system (CNS) at screening
3.Any 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.
4.Major surgery within 4 weeks before the first dose of study drug.
5.Inability 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
6. Subjects currently taking medications that are known moderate or strong CYP3A inducers (refer to Appendix 7 for a list of example drugs)
oIf 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
7.Vaccinated with live, attenuated vaccines within 6 months of enrollment (except COVID vaccine)
8.Use of any standard or experimental anti-cancer drug therapy within 4 weeks or a minimum of 3 half lives of the drug, whatever the shortest prior to first administration of study drug,
9.History of CAR T-cells therapy within 30 days prior to the first dose of study drug
10.History of autologous or allogeneic HCT within 90 days prior to the first dose of study drug
11.Patients 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).
12.Participant 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
13.Subjects 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).
14.Positive serology of human immunodeficiency virus (HIV)
15.Participant with prolongation of corrected QT interval using Fridericia's formula (QTcF) to > 470 milliseconds (msec) (obtained on average of 3 ECGs)
16.Participant with venous thrombosis or pulmonary embolism not treated
17.Participant with complications of hepatic cirrhosis, interstitial pneumonia, or pulmonary fibrosis
18.Participant with active infection requiring systemic therapy
19.Woman who are pregnant (positive serum pregnancy test at screening) or breastfeeding
20. Participant who were deemed as inappropriate to participate in the study by the investigator or sub-investigator

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified