Cinobufacini Tablets Combined With Chemotherapeutic Protocol in Treatment of Diffuse Large B Cell Lymphoma

Diffuse, Large B-Cell, Lymphoma Clinical Trial

Official title:

Cinobufacini Tablets Combined With R-CHOP Protocol (Rituximab + Vindesine + Cyclophosphamide + Epirubicin + Prednisone)/CHOP in Treatment of Diffuse Large B Cell Lymphoma: A Phase II Randomized, Controlled and Multi-center Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02871869
• Other study ID #: XinjiangMU2016(015)V2.0
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: August 12, 2016
• Last updated: July 12, 2017
• Start date: September 2016
• Est. completion date: December 2021

Study information

• Verified date: July 2017
• Source: Xinjiang Medical University
• Contact: Shun-E Yang, Professor
• Phone: 13669926688
• Email: yangshune[@]medmail.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Diffuse large B cell lymphoma (DLBCL), as the most common subtype non-Hodgkin lymphoma (NHL), has great heterogeneity in clinical manifestations, histological morphology and prognosis. R-CHOP Protocol (Rituximab + Vindesine + Cyclophosphamide + Epirubicin + Prednisone) is the gold therapeutic criteria for patients with NHL, and it is also used as the first-line treatment for patients with DLBCL. After treatment, 50％～60％of patients with DLBCL receive complete remission (CR), 30％～40％ recurrent and 10% will never be cured due to initial and secondary drug tolerance. This study aimed to explore whether Cinobufacini Tablets had synergistic effect in the treatment of DLBCL, and whether its action was in close association with the positive expression of Na+/K+-ATPase α3, and to observe the rates of adverse reactions induced by Cinobufacini Tablets during treatment.

Description:

Diffuse large B cell lymphoma (DLBCL), as the most common subtype non-Hodgkin lymphoma (NHL), accounts for 30％～40％ of adults with NHL, and has great heterogeneity in clinical manifestations, histological morphology and prognosis. R-CHOP Protocol (Rituximab + Vindesine + Cyclophosphamide + Epirubicin + Prednisone) is the gold therapeutic criteria for patients with NHL, and it is also used as the first-line treatment for patients with DLBCL. After treatment, 50％～60％of patients with DLBCL receive complete remission (CR), 30％～40％ recurrent and 10% will never be cured due to initial and secondary drug tolerance. The study of Tao Wu et al in domestic showed that cinobufacini combined with CHOP protocol had excellent efficacy in the treatment of NHL, with response rate reaching up to 91.7%, and the adverse reactions were mild and tolerable, whereas the response rate of single CHOP was only 62.5%. In the clinical practice of our studies, it was also found that some patients with recurrent DLBCL NHL also had shrunken or disappeared tumors and a survival time of more than 2 years after single administration of cinobufacini tablets for 3~6 months following the withdrawal of chemotherapy. This study aimed to explore whether Cinobufacini Tablets had synergistic effect in the treatment of DLBCL, and whether its action was in close association with the positive expression of Na+/K+-ATPase α3, and to observe the rates of adverse reactions induced by Cinobufacini Tablets during treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 316
• Est. completion date: December 2021
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

For control and trial groups A:

Inclusion Criteria:

• Patients aged 18-70 years old;

• Patients with eastern Collaborative Oncology Group (ECOG) performance status (PS) score: 0~3 points;

• International prognostic index (IPI): =3 points;

• Patients who were diagnosed as diffuse large B cell lymphoma (DLBCL) with initial treatment by histopathology;

• Patients with more than 1 measurable nidus (common CT or MRI scanning diameter = 20 mm, and spiral CT scanning diameter = 10 mm);

• Patients without dysfunction of important organs, and had normal blood routine, hepatorenal function and cardiac function. White blood cell count (WBC) =4.0×109/L, neutrophil count =1.5×109/L; platelet (PLT) count =100×109/L; hemoglobin (HGB) =95g/L; serum bilirubin (Bil) =1.5 folds of the upper limit of normal value, alanine transaminase (ALT) and aspartate aminotransferase (AST) =2 folds of the upper limit of normal value, and serum creatinine (Scr) =1.5mg/dl;

• Patients with expected survival time>3 months;

• Patients who were well informed of this study and signed the informed consent forms.

• Patients who received administration of Rituximab.

Exclusion Criteria:

• Patients who did not conform to above criteria;

• Patients who were receiving other anti-cancer therapies;

• Patients with DLBCL affected by primary breast gland, lung, testis, bone, peri-orbit, peri-spine, central nerve system and bone marrow;

• Patients with double expression, double strike, trinary expression and trinary strike and CD5+;

• Patients complicated with other non-DLBCL primary malignant tumors;

• Patients who had poor compliance with their families;

• Patients with one of the following conditions: uncontrolled metastatic nidi of central nerve system, dysfunction of important organs and severe cardiac diseases like congestive heart failure, uncontrollable arrhythmia, angina pectoris that needed long-term drug administration, valvular heart diseases, myocardial infarction and refractory hypertension, pregnancy or lactation, chronic infectious wounds, and history of uncontrollable psychological diseases.

• Patients had previous history of treatment with Cinobufacini Tablets.

For control and trial groups B

Inclusion Criteria:

• Patients aged 18-70 years old;

• Patients with eastern Collaborative Oncology Group (ECOG) performance status (PS) score: 0~3 points;

• International prognostic index (IPI): =3 points;

• Patients who were diagnosed as diffuse large B cell lymphoma (DLBCL) with initial treatment by histopathology;

• Patients with more than 1 measurable nidus (common CT or MRI scanning diameter = 20 mm, and spiral CT scanning diameter = 10 mm);

• Patients without dysfunction of important organs, and had normal blood routine, hepatorenal function and cardiac function. White blood cell count (WBC) =4.0×109/L, neutrophil count =1.5×109/L; platelet (PLT) count =100×109/L; hemoglobin (HGB) =95g/L; serum bilirubin (Bil) =1.5 folds of the upper limit of normal value, alanine transaminase (ALT) and aspartate aminotransferase (AST) =2 folds of the upper limit of normal value, and serum creatinine (Scr) =1.5mg/dl;

• Patients with expected survival time>3 months;

• Patients who were well informed of this study and signed the informed consent forms.

• Patients who did not receive administration of Rituximab.

Exclusion Criteria:

• Patients who did not conform to above criteria;

• Patients who were receiving other anti-cancer therapies;

• Patients with DLBCL affected by primary breast gland, lung, testis, bone, peri-orbit, peri-spine, central nerve system and bone marrow;

• Patients with double expression, double strike, trinary expression and trinary strike and CD5+;

• Patients complicated with other non-DLBCL primary malignant tumors;

• Patients who had poor compliance with their families;

• Patients with one of the following conditions: uncontrolled metastatic nidi of central nerve system, dysfunction of important organs and severe cardiac diseases like congestive heart failure, uncontrollable arrhythmia, angina pectoris that needed long-term drug administration, valvular heart diseases, myocardial infarction and refractory hypertension, pregnancy or lactation, chronic infectious wounds, and history of uncontrollable psychological diseases.

• Patients had previous history of treatment with Cinobufacini Tablets.

Related Conditions & MeSH terms

• Diffuse, Large B-Cell, Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• vindesine
3 mg/? (maximum dosage: <4mg), d1, 21 d as a cycle, for 4~6 cycles
• cyclophosphamide
750 mg/?, d1, 21 d as a cycle, for 4~6 cycles
• Epirubicin
60 mg/?, d1, 21 d as a cycle, for 4~6 cycles
• prednisone tablets
100 mg, d1~5, 21 d as a cycle, for 4~6 cycles
• Cinobufacini Tablets
0.3 g per tablet, 3 tablets per time, tid., p.o., until progressive disease or intolerable drug toxicities
• Rituximab
375mg/?,one day before CHOP protocol

Locations

Country	Name	City	State
China	Cancer Hospital Affiliated to Xinjiang Medical University	Ürümqi	Xinjiang

Sponsors (1)

Lead Sponsor	Collaborator
Xinjiang Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	3-year Progression-free survival (PFS) defined as the ratio of study subjects who had disease progression or died within 3 years from the start of randomization.	3 years
Secondary	Overall response rate (ORR)	Overall response rate (ORR) that defined as the total ratio of study subjects with complete response, complete response unconfirmed and partial response after treatment. ORR=(CR+ CRu+ PR)cases/total cases×100%.	2 years
Secondary	overall survival rate (OS)	3-year overall survival rate (OS) that defined as the ratio of study subjects who survived 3 years after randomization	3 years
Secondary	Safety and Tolerability	Incidence of Treatment-Emergent adverse events	2 years
Secondary	Relationship between synergistic effect of Cinobufacini Tablets and expression of Na+/K+-ATPase a3	Relationship between synergistic effect of Cinobufacini Tablets and expression of Na+/K+-ATPase a3	2 years