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

Primary Purpose

Diffuse, Large B-Cell, Lymphoma

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

vindesine

cyclophosphamide

Epirubicin

prednisone tablets

Cinobufacini Tablets

Rituximab

About this trial

This is an interventional treatment trial for Diffuse, Large B-Cell, Lymphoma focused on measuring Cinobufacini Tablets, CHOP protocol

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Cancer Hospital Affiliated to Xinjiang Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Active Comparator

Experimental

Arm Label

Control group A

Trial group A

Control group B

Trial group B

Arm Description

Control group A was treated with single R-CHOP protocol[Rituximab 375mg/㎡,one day before CHOP protocol, CHOP protocol included vindesine 3 mg/㎡ (maximum dosage: <4mg) d1 plus cyclophosphamide 750 mg/㎡ d1 plus Epirubicin 60 mg/㎡ d1 plus prednisone tablets 100 mg, d1～5], 21 d as a cycle, for 4～6 cycles.

Trial group A was treated with Cinobufacini Tablets combined with R-CHOP protocol[Rituximab 375mg/㎡,one day before CHOP protocol, CHOP protocol included vindesine 3 mg/㎡ (maximum dosage: <4mg) d1 plus cyclophosphamide 750 mg/㎡ d1 plus Epirubicin 60 mg/㎡d1 plus prednisone tablets 100 mg, d1～5], 21 d as a cycle, for 4～6 cycles.

Control group B was treated with single CHOP protocol[vindesine 3 mg/㎡ (maximum dosage: <4mg) d1 plus cyclophosphamide 750 mg/㎡ d1 plus Epirubicin 60 mg/㎡ d1 plus prednisone tablets 100 mg, d1～5], 21 d as a cycle, for 4～6 cycles.

Trial group B was treated with Cinobufacini Tablets combined with CHOP protocol[vindesine 3 mg/㎡ (maximum dosage: <4mg) d1 plus cyclophosphamide 750 mg/㎡ d1 plus Epirubicin 60 mg/㎡ d1 plus prednisone tablets 100 mg, d1～5], 21 d as a cycle, for 4～6 cycles.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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%.

overall survival rate (OS)

3-year overall survival rate (OS) that defined as the ratio of study subjects who survived 3 years after randomization

Safety and Tolerability

Incidence of Treatment-Emergent adverse events

Relationship between synergistic effect of Cinobufacini Tablets and expression of Na+/K+-ATPase α3

Full Information

NCT ID

NCT02871869

First Posted

August 12, 2016

Last Updated

July 12, 2017

Sponsor

Xinjiang Medical University

1. Study Identification

Unique Protocol Identification Number

NCT02871869

Brief Title

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

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Unknown status

Study Start Date

September 2016 (undefined)

Primary Completion Date

September 2018 (Anticipated)

Study Completion Date

December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Xinjiang Medical University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diffuse, Large B-Cell, Lymphoma

Keywords

Cinobufacini Tablets, CHOP protocol

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

316 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Control group A

Arm Type

Active Comparator

Arm Description

Arm Title

Trial group A

Arm Type

Experimental

Arm Description

Arm Title

Control group B

Arm Type

Active Comparator

Arm Description

Arm Title

Trial group B

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

vindesine

Other Intervention Name(s)

eldisine

Intervention Description

3 mg/㎡ (maximum dosage: <4mg), d1, 21 d as a cycle, for 4～6 cycles

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Other Intervention Name(s)

endoxan

Intervention Description

750 mg/㎡, d1, 21 d as a cycle, for 4～6 cycles

Intervention Type

Drug

Intervention Name(s)

Epirubicin

Other Intervention Name(s)

EPI

Intervention Description

60 mg/㎡, d1, 21 d as a cycle, for 4～6 cycles

Intervention Type

Drug

Intervention Name(s)

prednisone tablets

Other Intervention Name(s)

metacortandracin

Intervention Description

100 mg, d1～5, 21 d as a cycle, for 4～6 cycles

Intervention Type

Drug

Intervention Name(s)

Cinobufacini Tablets

Other Intervention Name(s)

buformin

Intervention Description

0.3 g per tablet, 3 tablets per time, tid., p.o., until progressive disease or intolerable drug toxicities

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

RTX

Intervention Description

375mg/㎡,one day before CHOP protocol

Primary Outcome Measure Information:

Title

Progression-free survival (PFS)

Description

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.

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Overall response rate (ORR)

Description

Time Frame

2 years

Title

overall survival rate (OS)

Description

3-year overall survival rate (OS) that defined as the ratio of study subjects who survived 3 years after randomization

Time Frame

3 years

Title

Safety and Tolerability

Description

Incidence of Treatment-Emergent adverse events

Time Frame

2 years

Title

Relationship between synergistic effect of Cinobufacini Tablets and expression of Na+/K+-ATPase α3

Description

Relationship between synergistic effect of Cinobufacini Tablets and expression of Na+/K+-ATPase α3

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Shun-E Yang, Professor

Phone

13669926688

yangshune@medmail.com.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shun-E Yang, Professor

Organizational Affiliation

Cancer Hospital Affiliated to Xinjiang Medical University

Official's Role

Study Chair

Facility Information:

Facility Name

Cancer Hospital Affiliated to Xinjiang Medical University

City

Ürümqi

State/Province

Xinjiang

ZIP/Postal Code

830011

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shun-E Yang, Professor

Phone

13669926688

yangshune@medmail.com.cn

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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