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

July 12, 2017 updated by: Shun-E Yang, Xinjiang Medical University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
316

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Xinjiang
      • Ürümqi, Xinjiang, China, 830011
        • Recruiting
        • Cancer Hospital affiliated to Xinjiang Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Control group A
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.
Drug: vindesine
3 mg/㎡ (maximum dosage: <4mg), d1, 21 d as a cycle, for 4～6 cycles
Other Names:
  • eldisine
Drug: cyclophosphamide
750 mg/㎡, d1, 21 d as a cycle, for 4～6 cycles
Other Names:
  • endoxan
Drug: Epirubicin
60 mg/㎡, d1, 21 d as a cycle, for 4～6 cycles
Other Names:
  • EPI
Drug: prednisone tablets
100 mg, d1～5, 21 d as a cycle, for 4～6 cycles
Other Names:
  • metacortandracin
Drug: Rituximab
375mg/㎡,one day before CHOP protocol
Other Names:
  • RTX
Experimental: Trial group A
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.
Drug: vindesine
3 mg/㎡ (maximum dosage: <4mg), d1, 21 d as a cycle, for 4～6 cycles
Other Names:
  • eldisine
Drug: cyclophosphamide
750 mg/㎡, d1, 21 d as a cycle, for 4～6 cycles
Other Names:
  • endoxan
Drug: Epirubicin
60 mg/㎡, d1, 21 d as a cycle, for 4～6 cycles
Other Names:
  • EPI
Drug: prednisone tablets
100 mg, d1～5, 21 d as a cycle, for 4～6 cycles
Other Names:
  • metacortandracin
Drug: Rituximab
375mg/㎡,one day before CHOP protocol
Other Names:
  • RTX
Drug: Cinobufacini Tablets
0.3 g per tablet, 3 tablets per time, tid., p.o., until progressive disease or intolerable drug toxicities
Other Names:
  • buformin
Active Comparator: Control group B
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.
Drug: vindesine
3 mg/㎡ (maximum dosage: <4mg), d1, 21 d as a cycle, for 4～6 cycles
Other Names:
  • eldisine
Drug: cyclophosphamide
750 mg/㎡, d1, 21 d as a cycle, for 4～6 cycles
Other Names:
  • endoxan
Drug: Epirubicin
60 mg/㎡, d1, 21 d as a cycle, for 4～6 cycles
Other Names:
  • EPI
Drug: prednisone tablets
100 mg, d1～5, 21 d as a cycle, for 4～6 cycles
Other Names:
  • metacortandracin
Experimental: Trial group B
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.
Drug: vindesine
3 mg/㎡ (maximum dosage: <4mg), d1, 21 d as a cycle, for 4～6 cycles
Other Names:
  • eldisine
Drug: cyclophosphamide
750 mg/㎡, d1, 21 d as a cycle, for 4～6 cycles
Other Names:
  • endoxan
Drug: Epirubicin
60 mg/㎡, d1, 21 d as a cycle, for 4～6 cycles
Other Names:
  • EPI
Drug: prednisone tablets
100 mg, d1～5, 21 d as a cycle, for 4～6 cycles
Other Names:
  • metacortandracin
Drug: Cinobufacini Tablets
0.3 g per tablet, 3 tablets per time, tid., p.o., until progressive disease or intolerable drug toxicities
Other Names:
  • buformin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 3 years
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: 2 years
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
overall survival rate (OS)
Time Frame: 3 years
3-year overall survival rate (OS) that defined as the ratio of study subjects who survived 3 years after randomization
3 years
Safety and Tolerability
Time Frame: 2 years
Incidence of Treatment-Emergent adverse events
2 years
Relationship between synergistic effect of Cinobufacini Tablets and expression of Na+/K+-ATPase α3
Time Frame: 2 years
Relationship between synergistic effect of Cinobufacini Tablets and expression of Na+/K+-ATPase α3
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Xinjiang Medical University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Shun-E Yang, Professor, Cancer Hospital affiliated to Xinjiang Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2016

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 12, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 16, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 18, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 17, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 12, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • XinjiangMU2016(015)V2.0

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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