SELINEXOR for Peripheral T-cell lymphoma (relapsed or refractory)

Inclusion criteria

• {"criterion_text":"- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care\n- Patients must be accessible for treatment and follow up as well as they must be willing and capable to comply with the requirements of the study\n- Confirmed availability of archival or freshly collected tumor tissue\n- Life expectancy of at least 3 months\n- Absence of central nervous system (CNS) involvement at the moment of enrollment\n- No previous medical history of psychiatric disease\n- Normal organ function: clearance creatininine ≥ 40 mL/min; ejection fraction > 50%; Levels of serum bilirubin, alkaline phosphatase and transaminases < 2 the upper normal limit, if not disease related\n- Histologically confirmed diagnosis of angioimmunoblastic T cell lymphoma (AITL), anaplastic large cell lymphoma ALK negative lymphoma (ALK neg), peripheral T cell lymphoma not otherwise specified (PTCL-NOS), or T helper follicular lymphoma (TFH) according to 2016 WHO classification\n- Age > 18 and < 75\n- Must have measurable disease defined by at least 1 fluorodeoxyglucose (FDG)-avid lesion for FDG-avid subtype and 1 bi-dimensionally measurable (> 1.5 cm in longest diameter) disease by computed tomography (CT) or magnetic resonance imaging (MRI), as defined by the Lugano classification\n- Eastern Cooperative Oncology Group (ECOG) performance status of ECOG ≤2\n- Female patients of reproductive potential should avoid becoming pregnant by using a highly effective method of contraception or abstaining from sexual activity while being treated with selinexor and for at least 90 days following the last dose of selinexor. Female subject is either: • post-menopausal for at least one year before the screening visit, or • surgically sterilized, or • willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.\n- Male patients of reproductive potential should use an effective method of contraception and are recommended to use a barrier method or abstain from sexual activity while being treated with selinexor and for at least 90 days following the last dose of selinexor. Male subject, even if surgically sterilized (ie, status postvasectomy), agrees to use an acceptable method for contraception during the entire study treatment period through 90 days following the last dose of selinexor\n- Relapsed or refractory disease after at least one previous line of anti-lymphoma treatment containing anthracycline (including or not high dose chemotherapy and stem cell transplantation as part of the program)\n- Must have the following laboratory values: a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L or ≥ 1.0 x 109/L in case of documented bone marrow involvement (> 50% or tumor cells), without growth factor support for 7 days (14 days if pegfilgrastim). b. untransfused Hemoglobin (Hb) ≥ 8 g/dL. c. Platelets (PLT) ≥ 75 x 109/L or ≥ 50 x 109/L in case of documented bone marrow involvement (> 50% or tumor cells), without transfusion for 7 days. d. Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase / serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x ULN. e. Serum total bilirubin ≤ 1.5 ULN except in cases of Gilbert’s syndrome, then ≤ 3.0 ULN. f. Estimated serum creatinine clearance of ≥ 40 mL/min using the modification of diet in renal disease formula or directly determined from the 24-hour urine collection method."}

Exclusion criteria

• {"criterion_text":"- Any significant medical condition, or psychiatric illness that would prevent the subject from participating in the study\n- Contraindication to any of the required concomitant drugs or supportive treatments\n- Patient has received other investigational drugs within 30 days before enrollment\n- Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study\n- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy\n- Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study\n- Active, unstable cardiovascular function, as indicated by the presence of: o Symptomatic ischemia, or o Uncontrolled clinically significant conduction abnormalities (eg, patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or o Congestive heart failure of New York Heart Association Class ≥3 or known left ventricular ejection fraction <40%, or o Myocardial infarction within 6 months prior to C1D1\n- Female subject who is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.\n- Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to treatment initiation are acceptable\n- Prior radiation therapy within 30 days prior to starting SIDE\n- Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant. Prior to study entry, any ECHO or MUGA scan abnormality at Screening has to be documented by the investigator as not medically relevant\n- Subjects with active hepatitis B virus (HBV) or active hepatitis C (HCV)\n- Known seropositivity for or active viral infection with human immunodeficiency virus (HIV)\n- Any active gastrointestinal dysfunction interfering with the patient’s ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment"}

Primary endpoints

• {"endpoint_text":"- ORR at the end of 4 courses of S-IDE","definition_or_measurement_approach":"Overall response rate (ORR) defined as complete response plus partial response after 4 courses of selinexor combined with ifosfamide, etoposide and dexamethasone (as defined in main objective and Lugano classification for response assessment)."}

Secondary endpoints

• {"endpoint_text":"- DOR","definition_or_measurement_approach":"Duration of response (time from first documented response to progression or death)."}
• {"endpoint_text":"- 18-months PFS","definition_or_measurement_approach":"Progression-free survival at 18 months (time from treatment start to disease progression or death)."}
• {"endpoint_text":"- 18-months OS","definition_or_measurement_approach":"Overall survival at 18 months (time from treatment start to death from any cause)."}
• {"endpoint_text":"- TRM","definition_or_measurement_approach":"Treatment Related Mortality (deaths attributed to treatment)."}
• {"endpoint_text":"- CR by histotypes","definition_or_measurement_approach":"Complete response rate (CR) stratified by histotypes (AITL, ALK neg, PTCL-NOS, TFH)."}
• {"endpoint_text":"- Proportion of patients able to undergo SCT","definition_or_measurement_approach":"Proportion of patients who proceed to allogeneic stem cell transplant (SCT) after S-IDE treatment."}
• {"endpoint_text":"- Adverse events (grading/onset/severity) according to SOC and within the CTCAE v.5.0 category","definition_or_measurement_approach":"Safety assessed by adverse events graded by Common Terminology Criteria for Adverse Events v5.0, reported by system organ class (SOC) with onset and severity."}

Italy

Earliest CTIS Part Ii Submission Date

28-03-2024

Latest Decision Or Authorization Date

18-11-2025

Processing Time Days

600

Number Of Sites

9

Number Of Participants

30

Primary sponsor

Full Name

Fondazione IRCCS Istituto Nazionale Dei Tumori

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy