Selinexor, High-dose Methotrexate, and Rituximab Combined With Radiotherapy for Newly Diagnosed, Transplant-ineligible Patients With Central Nervous System Lymphoma: An Open-label, Single-arm, Multicenter Phase II Study

NCT07002099 | Recruiting Phase 2

• 1 other identifier: LK2024097
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II clinical trial is designed to evaluate a novel combination treatment for patients with newly diagnosed central nervous system lymphoma (CNSL) who are not candidates for stem cell transplantation. The study will assess the safety and effectiveness of combining selinexor (an oral selective nuclear export inhibitor) with high-dose methotrexate and rituximab chemotherapy, followed by low-dose whole-brain radiotherapy (WBRT). Selinexor has shown promise in enhancing the effects of chemotherapy and radiation in blood cancers. Patients enrolled in this open-label, single-arm, multicenter study will receive up to six 21-day treatment cycles. Those who respond well will undergo reduced-dose WBRT and continue selinexor as maintenance therapy. The study will measure how many patients respond to the treatment (overall response rate), how long the response lasts (progression-free survival), overall survival, and safety. This research aims to provide a less toxic and more effective option for treating CNSL in patients who are older or medically unfit for transplantation.

Conditions

Lymphomas

Keywords

Selinexor; central nervous system lymphoma; WBRT

Outcome Measures

Primary Outcomes (1)

• ORR

  The proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by investigators according to the 2014 Lugano classification for lymphoma response evaluation.

  2 years

Secondary Outcomes (1)

• PFS

  2 years

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Participants in this single-arm study will receive combination therapy as follows: Rituximab 375 mg/m² intravenously on Day 0 of each 21-day cycle High-dose Methotrexate (HD-MTX) 3.5 g/m² intravenously over 4 hours on Day 1 of each cycle Selinexor 80 mg orally once weekly (on Days 1, 8, and 15) during each cycle Treatment is administered every 21 days for up to 6 cycles. Tumor response will be evaluated every 3 cycles. Patients who achieve a partial response (PR) or better will undergo consolidative low-dose whole-brain radiotherapy (WBRT) at 23.4 Gy in 13 fractions. After radiotherapy, patients who maintain a response will continue with maintenance selinexor 80 mg orally once weekly until disease progression, unacceptable toxicity, or withdrawal. This arm is designed to assess the synergistic effect of selinexor when combined with standard CNSL chemotherapy and radiotherapy in patients who are not eligible for stem cell transplantation.

Drug: Selinexor + High-dose Methotrexate + Rituximab + WBRT

Interventions

Selinexor + High-dose Methotrexate + Rituximab + WBRT DRUG

Rituximab 375 mg/m² intravenously on Day 0 of each 21-day cycle High-dose Methotrexate (HD-MTX) 3.5 g/m² intravenously over 4 hours on Day 1 of each cycle Selinexor 80 mg orally once weekly (on Days 1, 8, and 15) during each cycle Treatment is administered every 21 days for up to 6 cycles. Tumor response will be evaluated every 3 cycles. Patients who achieve a partial response (PR) or better will undergo consolidative low-dose whole-brain radiotherapy (WBRT) at 23.4 Gy in 13 fractions.

Experimental Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years, male or female.
• Histologically confirmed primary CNS lymphoma (PCNSL) or secondary CNS lymphoma (SCNSL) with CNS-only involvement.
• Ineligible for autologous stem cell transplantation based on clinical assessment or patient refusal.
• At least one measurable brain lesion ≥1 cm in diameter, or positive cerebrospinal fluid (CSF) cytology/flow cytometry for patients with leptomeningeal disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
• Adequate organ function, including:
• Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L
• Platelets ≥ 75 × 10⁹/L
• Hemoglobin ≥ 80 g/L
• Total bilirubin ≤ 1.5 × ULN (or ≤ 3 × ULN if liver involvement)
• ALT and AST ≤ 2.5 × ULN (or ≤ 5 × ULN if liver involvement)
• Creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)
• INR ≤ 1.5 × ULN; APTT within 10 seconds of normal
• Estimated life expectancy of ≥ 3 months.
• Negative serum pregnancy test for women of childbearing potential.

You may not qualify if:

• CNS involvement limited to intraocular lymphoma only.
• Prior systemic therapy for CNS lymphoma.
• SCNSL with active systemic (non-CNS) disease involvement.
• Uncontrolled intracranial hypertension.
• Clinically significant or unstable cardiovascular disease, including:
• Myocardial infarction within 6 months
• Unstable angina within 3 months
• Uncontrolled arrhythmias (e.g., ventricular tachycardia/fibrillation)
• Congestive heart failure NYHA class ≥ III
• LVEF \< 50% by echocardiography
• Other severe uncontrolled medical conditions, including active infections requiring systemic therapy.
• Known active hepatitis B (HBV), hepatitis C (HCV), or HIV infection.
• Active gastrointestinal dysfunction that interferes with the ability to swallow or absorb oral medication.
• Prior treatment with selective inhibitor of nuclear export (SINE) compounds, including selinexor.
• Concurrent malignancy, except for adequately treated basal/squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the cervix, prostate, or breast.

Sponsors & Collaborators

• Second Affiliated Hospital of Soochow University: lead

Study Sites (1)

The Second Affiliated Hospital of Soochow University

Suzhou, 215000, China

RECRUITING

Related Publications (6)

• Houillier C, Soussain C, Ghesquieres H, Soubeyran P, Chinot O, Taillandier L, Lamy T, Choquet S, Ahle G, Damaj G, Agape P, Molucon-Chabrot C, Amiel A, Delwail V, Fabbro M, Jardin F, Chauchet A, Moles-Moreau MP, Morschhauser F, Casasnovas O, Gressin R, Fornecker LM, Abraham J, Marolleau JP, Tempescul A, Campello C, Colin P, Tamburini J, Laribi K, Serrier C, Haioun C, Chebrek S, Schmitt A, Blonski M, Houot R, Boyle E, Bay JO, Oberic L, Tabouret E, Waultier A, Martin-Duverneuil N, Touitou V, Cassoux N, Kas A, Mokhtari K, Charlotte F, Alentorn A, Feuvret L, Le Garff-Tavernier M, Costopoulos M, Mathon B, Peyre M, Delgadillo D, Douzane H, Genet D, Aidaoui B, Hoang-Xuan K, Gyan E. Management and outcome of primary CNS lymphoma in the modern era: An LOC network study. Neurology. 2020 Mar 10;94(10):e1027-e1039. doi: 10.1212/WNL.0000000000008900. Epub 2020 Jan 6.

  PMID: 31907289 BACKGROUND

• Walker JS, Garzon R, Lapalombella R. Selinexor for advanced hematologic malignancies. Leuk Lymphoma. 2020 Oct;61(10):2335-2350. doi: 10.1080/10428194.2020.1775210. Epub 2020 Jun 14.

  PMID: 32536290 BACKGROUND

• Neupane K, Wahab A, Masood A, Faraz T, Bahram S, Ehsan H, Hannan A, Anwer F. Profile and Management of Toxicity of Selinexor and Belantamab Mafodotin for the Treatment of Triple Class Refractory Multiple Myeloma. J Blood Med. 2021 Jul 1;12:529-550. doi: 10.2147/JBM.S317966. eCollection 2021.

  PMID: 34234609 BACKGROUND

• Lurain K, Uldrick TS, Ramaswami R, Polizzotto MN, Goncalves PH, Widell A, Steinberg SM, Jaffe ES, Pittaluga S, Wang HW, Yuan CM, Tamula MA, Martin S, Wolters PL, George J, Little RF, Yarchoan R. Treatment of HIV-associated primary CNS lymphoma with antiretroviral therapy, rituximab, and high-dose methotrexate. Blood. 2020 Nov 5;136(19):2229-2232. doi: 10.1182/blood.2020006048. No abstract available.

  PMID: 32609814 BACKGROUND

• Gandhi MK, Hoang T, Law SC, Brosda S, O'Rourke K, Tobin JWD, Vari F, Murigneux V, Fink L, Gunawardana J, Gould C, Oey H, Bednarska K, Delecluse S, Trappe RU, Merida de Long L, Sabdia MB, Bhagat G, Hapgood G, Blyth E, Clancy L, Wight J, Hawkes E, Rimsza LM, Maguire A, Bojarczuk K, Chapuy B, Keane C. EBV-associated primary CNS lymphoma occurring after immunosuppression is a distinct immunobiological entity. Blood. 2021 Mar 18;137(11):1468-1477. doi: 10.1182/blood.2020008520.

  PMID: 33202420 BACKGROUND

• Ostrom QT, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018. Neuro Oncol. 2021 Oct 5;23(12 Suppl 2):iii1-iii105. doi: 10.1093/neuonc/noab200.

  PMID: 34608945 BACKGROUND

MeSH Terms

Conditions

Lymphoma

Interventions

selinexor; Methotrexate; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Bingzong Li

  Second Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bingzong Li

CONTACT

86-512-67784069; lbzwz0907@hotmail.com

Yuchen Zhang

CONTACT

+8615250035366; 1520287376@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2025
• First Posted: June 3, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 3, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)