Selinexor Combined With R-GemOx as Second-line Treatment in Patients With Diffuse Large B-cell Lymphoma

Diffuse Large B-Cell Lymphoma, Not Otherwise Specified Clinical Trial

Official title:

Selinexor Combined With R-GemOx as Second-line Treatment in Patients With Diffuse Large B-cell Lymphoma： a Single-arm, Single-centre, Open-label Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05786989
• Other study ID #: Chongqingcancer v3.0_20220908
• Status: Recruiting
• Phase: Phase 4
• Start date: February 28, 2023
• Est. completion date: September 30, 2024

Study information

• Verified date: March 2023
• Source: Chongqing University Cancer Hospital
• Contact: Yao Liu, MD
• Phone: 13228684685
• Email: liuyao77[@]cqu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this interventional study is to evaluate efficiency and safety in prior one-line treated diffuse large B-cell lymphoma. The main questions it aims to answer are:

• Complete remission rate

• Objective remission rate

• Progression-free survival

• tolerance Participants will recevied a minimum of 2 and a maximum of 6 cycles of R-GemOx(rituximab 375 mg/m2 IV on day 1 , Gemcitabine 1000 mg/m2, Oxaliplatin 100 mg/m2 IV on day 2) and 60 mg selinexor on days 1, 8, and 15 of each cycle

Description:

After the subject has completed at least 2 courses of treatment with Serenixol and R-GemOx for up to 6 courses, the patients who have reached ≥ partial remission (PR) and meet the conditions of transplantation can receive transplantation according to the institutional standards, and those who are not suitable for transplantation can receive maintenance treatment with Serenixol. In the maintenance treatment, the dose of Serenixol is 60 mg on the first day of the week until the disease progresses In case of intolerable toxicity or if the researcher believes that the patient is no longer suitable for study treatment, re-examine every 3 months in the first year, the second year and every 6 months after the end of transplantation or maintenance treatment; Patients with stable disease (SD) or disease progression (PD) after 2~6 courses of treatment will end the trial, and no survival follow-up will be conducted

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: September 30, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Have pathologically confirmed CD20 positive de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma)

• HIV-seropositive

• Age 18-75 years

• ECOG PS=2

• Positron emission tomography (PET) positive measurable disease with at least one node having the longest diameter (LDi)>1.5cm or one extranodal lesion with LDi>1cm (per the Lugano Criteria 2014) (Documentation to be provided)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 2.5 × Upper limit of normal value (ULN), or = 5 in the presence of known lymphoma involving the liver × ULN; Total serum bilirubin = 2 × ULN, or = 5 when Gilbert syndrome or known lymphoma affects the liver × ULN; Creatinine clearance (CrCl) calculated according to Cockcroft Gault formula = 30 mL/min;

• Absolute neutrophil count (ANC)=1.5×10^9/L,or Platelet count=75×10^9/L(No platelet were transfused within 14 days before the treatment of the study drug),or Hemoglobin=80g/L(No red blood cells were transfused within 14 days before the treatment of the study drug)

• Written informed consent in accordance with federal, local, and institutional guidelines

• Patients understanding the characteristics of the disease and voluntarily joins the study program for treatment and follow-up

• No other serious diseases in conflict with this program

• Investigator believe that subjects can benefit

Exclusion Criteria:

• Patients with known central nervous system involvement by lymphoma;

• Patients with a history of autoimmune diseases or syndrome requiring systemic use of steroid, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism and hypothyroidism

• Patients received systemic glucocorticoid (prednisone >20mg/d) or any other immunosuppressive therapy within 7 days before the first administration,excluding nasal spray inhalation or other topical glucocorticoids;

• Uncontrolled heart diseases, including unstable angina pectoris, acute myocardial infarction 6 months before randomization, congestive heart failure (NYHA), cardiac function grade greater than grade III or IV, or left ventricular ejection fraction<50%;

• Patients previously treated with selinexor;

• History of severe allergic reactions (as determined by treating physician) attributed to the drugs being used in the study;

• Patients undergoing organ transplantation;

• Diagnosed as malignant tumor other than lymphoma or receiving treatment,excluding:

1. Malignant tumors that have received treatment for the purpose of cure and have not developed known active diseases for = 5 years before enrollment

2. Basal cell carcinoma of the skin (excluding melanoma) with adequate treatment and no signs of disease

3. Cervical carcinoma in situ with adequate treatment and no signs of disease

• Patients with grade 2 or more neurotoxicity occurred within two weeks before treatment;

• Severe infection;

• Drug abuse, medical psychological or social conditions that may interfere with the subject's participation in the study or the evaluation of the results of the study;

• Any active, serious psychiatric, medical, or other conditions/situations which, in the treating physician's opinion, could compromise the patient's safety

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• selinexor
Given PO

Locations

Country	Name	City	State
China	Chongqing University Cancer Hospital	Chongqing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Chongqing University Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (17)

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Corazzelli G, Capobianco G, Arcamone M, Ballerini PF, Iannitto E, Russo F, Frigeri F, Becchimanzi C, Marcacci G, De Chiara A, Pinto A. Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligi — View Citation

Corno C, Stucchi S, De Cesare M, Carenini N, Stamatakos S, Ciusani E, Minoli L, Scanziani E, Argueta C, Landesman Y, Zaffaroni N, Gatti L, Perego P. FoxO-1 contributes to the efficacy of the combination of the XPO1 inhibitor selinexor and cisplatin in ova — View Citation

Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808. Blood. 2018 Feb 1;131(5):587-588. doi: 10.1182/blood-2017-11-817775. No abstract ava — View Citation

Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patient — View Citation

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Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Briere J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituxima — View Citation

Harris LJ, Patel K, Martin M. Novel Therapies for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Int J Mol Sci. 2020 Nov 13;21(22):8553. doi: 10.3390/ijms21228553. — View Citation

Kalakonda N, Maerevoet M, Cavallo F, Follows G, Goy A, Vermaat JSP, Casasnovas O, Hamad N, Zijlstra JM, Bakhshi S, Bouabdallah R, Choquet S, Gurion R, Hill B, Jaeger U, Sancho JM, Schuster M, Thieblemont C, De la Cruz F, Egyed M, Mishra S, Offner F, Vassi — View Citation

Kazim S, Malafa MP, Coppola D, Husain K, Zibadi S, Kashyap T, Crochiere M, Landesman Y, Rashal T, Sullivan DM, Mahipal A. Selective Nuclear Export Inhibitor KPT-330 Enhances the Antitumor Activity of Gemcitabine in Human Pancreatic Cancer. Mol Cancer Ther — View Citation

Krok-Schoen JL, Fisher JL, Stephens JA, Mims A, Ayyappan S, Woyach JA, Rosko AE. Incidence and survival of hematological cancers among adults ages >/=75 years. Cancer Med. 2018 Jul;7(7):3425-3433. doi: 10.1002/cam4.1461. Epub 2018 Apr 13. — View Citation

Mounier N, El Gnaoui T, Tilly H, Canioni D, Sebban C, Casasnovas RO, Delarue R, Sonet A, Beaussart P, Petrella T, Castaigne S, Bologna S, Salles G, Rahmouni A, Gaulard P, Haioun C. Rituximab plus gemcitabine and oxaliplatin in patients with refractory/rel — View Citation

Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, Lopez-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuh — View Citation

Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgk — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission rate	Response rates will be estimated as proportions with 95% Wilson confidence intervals	UP to 2 years
Secondary	Progression-free survival	PFS will be described with Kaplan-Meier curves and estimated medians with 95% confidence intervals	From baseline to disease progression or death from any cause, assessed up to 2 years
Secondary	Objective remission rate	Response rates will be estimated as proportions with 95% Wilson confidence intervals	UP to 2 years

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