Status:
RECRUITING
A Phase Ib/II Clinical Study Evaluating the Safety and Efficacy of Tislelizumab in Combination With Golidocitinib and Selinexor for the Treatment of R/R NKTCL
Lead Sponsor:
Fudan University
Conditions:
Natural Killer/T-cell Lymphoma
Relapsed or Refractory Lymphoma Including ENKL
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
This open-label, multicenter Ib/II phase clinical trial investigates the safety, tolerability, and preliminary efficacy of tislezumab (anti-PD-1 monoclonal antibody), golidocitinib (JAK1/STAT3 signali...
Detailed Description
This phase Ib/II open-label, multicenter clinical trial addresses the critical unmet need in relapsed/refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL), an aggressive Epstein-Barr virus...
Eligibility Criteria
Inclusion
- Voluntarily participate in the clinical study; fully understand and provide informed consent (via a signed Informed Consent Form, ICF); willing and able to comply with all trial procedures.
- Histopathologically confirmed diagnosis of extranodal NK/T-cell lymphoma, nasal type (NKTCL) by the participating study center.
- Relapsed or refractory NKTCL after failure of asparaginase-based chemotherapy ± radiotherapy:
- Relapse: Disease recurrence \>6 months after achieving complete response (CR) to prior therapy.
- Refractory: Failure to achieve CR or disease progression after adequate systemic therapy (≥4 cycles of a combination regimen).
- For Phase II: Patients must have received prior anti-PD-1 monoclonal antibody therapy and remain refractory.
- At least one measurable or evaluable lesion per Lugano 2014 criteria:
- Measurable lesion: CT/MRI: Longest diameter ≥1.5 cm (lymph nodes) or ≥1.0 cm (extranodal lesions).Post-radiation lesions require radiological evidence of progression.
- Evaluable lesion: FDG-PET: Lymph node/extranodal lesion with uptake \> liver and imaging consistent with lymphoma.
- Age ≥18 years at the time of ICF signing.
- Life expectancy \>12 weeks.
- ECOG performance status 0-2.
- Adequate organ and bone marrow function:
- Hematology (no transfusion/G-CSF support within 14 days): ANC ≥1.5×10⁹/L (≥0.5×10⁹/L if bone marrow involvement)；Platelets ≥100×10⁹/L (≥50×10⁹/L if bone marrow involvement)；Hemoglobin ≥8.0 g/dL.
- Liver function: Total bilirubin ≤1.5×ULN (≤3.0×ULN for Gilbert's syndrome or liver involvement).
- ALT/AST ≤2.5×ULN (≤5.0×ULN with liver involvement).
- Renal function: Serum creatinine ≤1.5×ULN OR creatinine clearance (Cockcroft-Gault) ≥50 mL/min.
- Coagulation: INR ≤1.5×ULN; PT/APTT ≤1.5×ULN (unless on anticoagulants within therapeutic range).
- Cardiac function: LVEF ≥50% by echocardiography (ECHO).
- Recovery from prior anticancer therapy toxicities to CTCAE v5.0 Grade ≤1 or baseline. Exceptions: Irreversible Grade 2 toxicities unlikely to worsen during the study (e.g., neuropathy, alopecia) per investigator's assessment.
- For women of childbearing potential (WOCBP): Negative serum pregnancy test within 7 days before enrollment. WOCBP and male participants with WOCBP partners must agree to use effective contraception from ICF signing until ≥6 months after the last study dose.
Exclusion
- History of malignancy within the past 5 years, with the exception of: Locally curable malignancies treated with curative intent (e.g., basal or squamous cell skin cancer, thyroid carcinoma, superficial bladder cancer, or in situ carcinoma of the prostate, cervix, or breast).
- Any of the following prior treatments:
- History of allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 5 years prior to the first dose (patients with allo-HSCT \>5 years before the first dose and no active graft-versus-host disease may enroll).
- Autologous hematopoietic stem cell transplantation (auto-HSCT) within 3 months prior to the first dose.
- Prior use of JAK inhibitors, STAT3 inhibitors, or XPO1 inhibitors.
- Current use of vitamin K antagonists, antiplatelet agents, or anticoagulants (or inability to discontinue within 1 week before the first dose).
- Systemic glucocorticoids or immunosuppressants within 14 days prior to enrollment (allowed: topical, ocular, intra-articular, intranasal, or inhaled glucocorticoids; short-term \[≤7 days\] prophylactic use for non-autoimmune conditions).
- Cytotoxic chemotherapy within 14 days prior to enrollment.
- Systemic anticancer therapy (including monoclonal antibodies or immunotherapy) within 4 weeks prior to the first dose.
- Major organ surgery within 6 weeks or radiotherapy within 90 days prior to enrollment.
- Radioimmunoconjugate therapy within 10 weeks prior to enrollment.
- Use of other investigational drugs requiring investigator's risk-benefit assessment.
- Participation in other clinical trials with investigational drugs within 30 days prior to enrollment.
- Vaccines (except influenza vaccines) within 28 days prior to enrollment.
- Active infections, including:
- Active or latent tuberculosis (positive tuberculin skin test \[PPD\] with induration ≥10 mm or radiologically confirmed active lesions).
- Known HIV infection or AIDS.
- Chronic active hepatitis B or C:
- HBV: Exclude if HBV DNA detectable (↑center-specific ULN). HCV: Exclude if HCV RNA detectable (↑center-specific ULN).
- Other active viral infections (e.g., herpes zoster, CMV) requiring treatment. Infections requiring intravenous antimicrobial therapy.
- Uncontrolled cardiac conditions, including:
- NYHA Class \>II heart failure.
- Unstable angina.
- Myocardial infarction within 1 year.
- Clinically significant arrhythmias requiring intervention.
- Persistent drug-related toxicities \>CTCAE Grade 1 (excluding alopecia) at baseline.
- Uncontrolled nausea/vomiting, chronic gastrointestinal diseases, dysphagia, or prior bowel resection affecting drug absorption.
- Pregnancy, lactation, or refusal to use contraception by participants of reproductive potential.
- Psychiatric disorders or inability to provide informed consent.
- Other conditions deemed unsuitable for study participation by the investigator.
Key Trial Info
Start Date :
May 26 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
May 30 2028
Estimated Enrollment :
68 Patients enrolled
Trial Details
Trial ID
NCT06966154
Start Date
May 26 2025
End Date
May 30 2028
Last Update
May 30 2025
Active Locations (1)
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1
Dept of lymphoma and medical oncology, Shanghai Cancer Center
Shanghai, Shangai, China, 200032