Pilot phase II study of Selinexor in combination with Ifosfamide, Etoposide and Dexamethasone (SIDE) in patients with relapsed or refractory Peripheral T-cell Lymphomas

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione IRCCS Istituto Nazionale Dei Tumori

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

10 Aug 2022 → ongoing

Decision date (initial)

2024-05-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513295-18-00

EudraCT number

2021-006229-23

WHO UTN

U0000-0000-0000

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

define the overall response rate (ORR) (complete response plus partial response) after 4 courses of selinexor when combined to ifosfamide, etoposide and dexamethasone

Secondary objectives 7

1. Duration of response, DOR
2. Progression Free Survival, PFS
3. Overall Survival, OS
4. Treatment Related Mortality, TRM
5. Complete Response rate (CR) by histotypes [angioimmunoblastic T cell lymphoma (AITL), anaplastic ALK negative lymphoma (ALK neg), peripheral T cell lymphoma not otherwise specified (PTCL-NOS), T helper follicular lymphoma (TFH)]
6. To assess the feasibility of the S-IDE treatment strategy combined with allogeneic SCT
7. To assess safety of the S-IDE treatment scheme

Conditions and MedDRA coding

Relapsed or Refractory Peripheral T-cell Lymphomas

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
2. 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
3. Age > 18 and < 75
4. 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
5. Eastern Cooperative Oncology Group (ECOG) performance status of ECOG ≤2
6. 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.
7. 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
8. 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)
9. 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.
10. 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
11. Confirmed availability of archival or freshly collected tumor tissue
12. Life expectancy of at least 3 months
13. Absence of central nervous system (CNS) involvement at the moment of enrollment
14. No previous medical history of psychiatric disease
15. 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

Exclusion criteria 14

1. Any significant medical condition, or psychiatric illness that would prevent the subject from participating in the study
2. 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
3. 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.
4. 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
5. Prior radiation therapy within 30 days prior to starting SIDE
6. 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
7. Subjects with active hepatitis B virus (HBV) or active hepatitis C (HCV)
8. Known seropositivity for or active viral infection with human immunodeficiency virus (HIV)
9. 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
10. Contraindication to any of the required concomitant drugs or supportive treatments
11. Patient has received other investigational drugs within 30 days before enrollment
12. 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
13. 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
14. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR at the end of 4 courses of S-IDE

Secondary endpoints 7

1. DOR
2. 18-months PFS
3. 18-months OS
4. TRM
5. CR by histotypes
6. Proportion of patients able to undergo SCT
7. Adverse events (grading/onset/severity) according to SOC and within the CTCAE v.5.0 category

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione IRCCS Istituto Nazionale Dei Tumori

Sponsor organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Address

Via Giacomo Venezian 1

City

Milan

Postcode

20133

Country

Italy

Scientific contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

S.C di Ematologia

Public contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

S.C di Ematologia

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications