Clinical trial NCT02871869: Cinobufacini Tablets Combined With Chemotherapeutic Protocol in Treatment of Diffuse Large B Cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Diffuse, Large B-Cell, Lymphoma
Keywords: Cinobufacini Tablets
CHOP protocol
Lead sponsor: Xinjiang Medical University
Sponsor class: OTHER
First posted: 2016-08-18
Enrollment: 316
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: 2 years
measure: overall survival rate (OS)
timeFrame: 3 years
measure: Safety and Tolerability
timeFrame: 2 years
measure: Relationship between synergistic effect of Cinobufacini Tablets and expression of Na+/K+-ATPase α3
timeFrame: 2 years
Other outcomes:
Locations:
city: Ürümqi
country: China
facility: Cancer Hospital Affiliated to Xinjiang Medical University
state: Xinjiang
Study officials:
affiliation: Cancer Hospital Affiliated to Xinjiang Medical University
name: Shun-E Yang, Professor
role: STUDY_CHAIR
References: