Selinexor, Anti-PD-1 Antibody and P-GemOx Regimen in R/R NKTCL

The Efficacy and Safety of Selinexor, Anti-PD-1 Antibody and P-GemOx Regimen in the Treatment of Relapsed or Refractory Natural Killer / T-cell Lymphoma

A multicenter, prospective trial to evaluate the efficacy and safety of Selinexor, anti-PD-1 antibody and P-GemOx in the treatment of relapsed or refractory Natural Killer / T-cell lymphoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Selinexor, anti-PD-1 antibody and P-GemOx

Detailed Description

This study aims to evaluate the efficacy and safety of Selinexor, anti-PD-1 antibody plus P-GemOx in relapsed or refractory NKTCL and find the optimal treatment regimen for patients with relapsed refractory NKTCL.

Patients receive 3 cycles of Selinexor, anti-PD-1 antibody plus P-GemOx, and then PET evaluation.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weili Zhao, Prof.; Phone Number: 008602164370045; Email: zwl_trial@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Confirmed histological diagnosis of NKTCL nasal type
2. The subject had received prior adequate anti-lymphoma therapy containing asparaginase
3. Age 14-75 years old
4. Expected to live longer than 3 months
5. At least one measurable/evaluable site after diagnostic biopsy before treatment start
6. ECOG performance status of 0-2
7. Adequate hematological and organ function; i.e. ANC >1000 cells /mmc, platelet counts > 50.000/mmc, Hemoglobin > 9 g/dl AST, ALT <3 x ULN; serum bilirubin < 1.5x ULN (patient with Gilbert disease can be enrolled) Serum creatinine < 2 x ULN or creatinine clearance > 50ml/min
8. Tumor tissue (fresh preferred, archival tissue is also acceptable)
9. For women of childbearing potential a negative pregnancy test on day 1 of cycle 1 and agree to adopt adequate measure to avoid pregnancy during study treatment and for at least one year from EOT.
10. For men agreement to remain abstinent or to use barrier contraception
11. Signed Informed consent

Exclusion Criteria:

1. Confirmed histological diagnosis of aggressive NK cell leukemia
2. Evidence of suspect of CNS disease.
3. Has an active autoimmune disease that has required systemic treatment in past 2-years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs), including but not limited to myotonia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associate with antiphospholipid syndrome, wegener's granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis or glomerulonephritis. The following exception are allowed: patients with autoimmune related hypothyroidism or type I diabetes mellitus who are on stable treatment. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
4. Treatment with systemic immunosuppressive medications, including prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide and anti tumor necrosis factor (anti-TNF) agents within 2 weeks prior to cycle 1 day 1; inhaled corticosteroids are allowed.
5. Active infection requiring systemic therapy
6. History of (non-infectious) pneumonitis that required steroids; evidence of interstitial lung disease or active, non-infectious pneumonitis
7. Significant cardiovascular disease, myocardial infarction in the previous 3 months, unstable arrhythmias, or unstable angina.
8. History of other(s) infiltrating cancer(s) in the previous 3 years that were not treated with curative intent or who are still receiving anticancer therapy (including hormone therapy for breast or prostate cancer).
9. HBsAg, HCV or HIV positivity. Positive serology is admitted for HBV and HCV but DNA/RNA test must be negative
10. Pregnant or lactating women
11. Administration of a live attenuated vaccine within 4 weeks before cyle 1 day 1. Patients must not receive live, attenuate vaccines, including influenza vaccines at any time during study.
12. Other uncontrollable medical condition that may interfere the participation of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemo; Patients receive 3 cycles of Selinexor, anti-PD-1 antibody plus P-GemOx.	Drug: Selinexor, anti-PD-1 antibody and P-GemOx; Selinexor, 40mg, qw, po; Pegaspargase, 2500U/m2, IM, d1; Gemcitabine, 1000mg/m2, i.v., d1, d8; Oxaliplatin, 130mg/m2, i.v., d1; anti-PD1 antibody, 200mg, d2, i.v. (21d cycle);

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best CRR	CRR defined according to 2014 Lugano criteria and 2016 Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy.	through study completion, an average of 1 year]

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: August 16, 2024
• First Submitted That Met QC Criteria: August 23, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): August 27, 2024
• Last Update Submitted That Met QC Criteria: August 23, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: RJ-NKTCL-5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No