Study of Orelabrutinib in Combination With Gemox in Refractory / Relapsed Diffuse Large B-cell Lymphoma

DLBCL Clinical Trial

— O-Gemox  

Official title:

A Phase II, Prospective, Multicenter Study Ofrelabrutinib in Combination With Gemox in Refractory / Relapsed Diffuse Large B-cell Lymphoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05381506
• Other study ID #: 2022-FXY-102-??
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2022
• Est. completion date: December 2025

Study information

• Verified date: May 2022
• Source: Sun Yat-sen University
• Contact: Zhiming Li, Dr.
• Phone: +86-020-87343765
• Email: lizhm[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to investigate the treatment of refractory or relapsed DLBCL with orelabrutinib and gemox. The primary endpoint is response rate (complete response rate and overall response rate), and the second endpoints are survival time (OS and PFS) and toxicities.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 77
• Est. completion date: December 2025
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically confirmed relapsed or refractory Diffuse Large B-cell Lymphoma. There must be at least one evaluate able or measurable lesion that meets the Lugano criteria

2. Age beyond18 years old;

3. ECOG performance status 0-2.

4. Estimated survival time > 12 weeks.

5. Adequate first-line treatment with CD20-containing monoclonal antibody

6. DLBCL patients confirmed as non-GCB by Han's classification

7. The main organs function well, namely, the following requirements were met one week before admission: Blood routine ANC = 1.5×109/L, Hb = 100g/L and PLT = 100×109/L; liver function were normal (total bilirubin =1.5×ULN, ALT and AST = 2.5×ULN), renal function was normal (serum creatinine =1×upper limitation of normal (ULN)), and without abnormal coagulation function.

8. Pregnant women of childbearing age must have a pregnancy test (serum or urine) within 14 days before enrollment and the result is negative, and they are willing to use reliable methods of contraception during the test.

9. The subjects who volunteer to join the study and sign the informed consent form, have good compliance and cooperate with the follow-up.

Exclusion Criteria:

1. Patients with central nervous system involvement

2. Patients with Myc gene and BCL2/BCL6 gene rearrangement at the same time;

3. Patients who have received BTK inhibitor therapy in the past;

4. Patients who have received Gemox or GDP chemotherapy in the past;

5. History of other malignancy within the last 5 years prior to enrollment, except for cured basal cell carcinoma of skin, cervix in situ carcinoma and superficial bladder cancer;

6. Suffering from the following cardiovascular diseases: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmia (including QTc interval = 450 ms for men and = 470 ms for women); according to NYHA standards, grades III to IV cardiac function Incomplete, or echocardiography showed left ventricular ejection fraction (LVEF) <50%;

7. Abnormal coagulation function (INR>1.5 or prothrombin time (PT)>ULN+4 seconds or APTT>1.5 ULN), with bleeding tendency or receiving thrombolysis or anticoagulation therapy;

8. Arterial/venous thrombotic events, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism, that occurred within 12 months before enrollment;

9. Known hereditary or acquired bleeding and thrombotic tendencies (such as hemophiliacs, coagulation disorders, thrombocytopenia, hypersplenism, etc.);

10. Received major surgical operation or suffered severe traumatic injury, fracture or ulcer within 4 weeks of enrollment;

11. There are factors that obviously affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea and intestinal obstruction;

12. Active infection requires antimicrobial treatment (for example, antibiotics and antiviral drugs are required, excluding chronic hepatitis B, anti-hepatitis B treatment, and antifungal drug treatment);

13. Active hepatitis B (HBV DNA = 2000IU/mL or 104 copies/mL) or hepatitis C (positive hepatitis C antibody, and HCV RNA is higher than the detection limit of the analytical method);

14. Those who have a history of psychotropic substance abuse and cannot quit or have mental disorders;

15. Participated in clinical trials of other anti-tumor drugs within 4 weeks before enrollment;

16. Received strong CYP3A4 inhibitor treatment within 7 days before enrollment, or received strong CYP3A4 inducer treatment within 12 days before participating in the study;

17. Pregnant or breastfeeding women; fertile patients who are unwilling or unable to take effective contraceptive measures;

18. The investigator judges other circumstances that may affect the conduct of clinical research and the judgment of research results.

Related Conditions & MeSH terms

• DLBCL
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Orelabrutinib and Gemox
Drug: Orelabrutinib Orelabrutinib 200mg, po, qd Drug: Gemox14 Gemcitabine, Oxaliplatin

Locations

Country	Name	City	State
China	Hunan Cancer Hospital	Changsha	Hunan
China	West China Hospital.Sichuan University	Chengdu	Sichuan
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	Guangxi Medical University Cancer Hospital	Naning	Guangxi
China	Tianjin Medical University Cancer Hospital	Tianjin	Tianjin
China	Hubei Cancer Hospital	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	overall response rate after treated by Orelabrutin and Gemox	12 weeks after the initiation of the treatment
Secondary	Progression Free Survival (PFS)	PFS was defined as time from study registration to first disease progression or death whichever occurred first, otherwise subject data were censored at time last known disease free	Up to two years after the start of the study
Secondary	Overall Survival (OS)	OS was defined as time from study registration to death, and otherwise censored at time last known alive	Up to two years after the start of the study
Secondary	Duration of Response(DOR)	The time from the first assessment of CR or PR to PD (progressive disease) or death from any cause	Up to three years after the start of the study
Secondary	Adverse events	All the adverse events of the patients related will be assessed and graded by NCI CTCAE v5.0	Up to one year after the start of the study