Clinical Study the Efficacy and Safety of Rh-EPO in the Treatment of Anemia in Lymphoma

Prospective, Open-label, Multicenter Clinical Study for the Efficacy and Safety of Recombinant Human Erythropoietin in the Treatment of Anemia in Patients With Lymphoma

The incidence of lymphoma and anemia is high and the clinical harm is great.However, it has not yet attracted enough clinical attention, and domestic rHuEPO (trade name: Ebio).Shenyang Sansheng Pharmaceutical Co., Ltd.) for lymphoma and anemia patients are less clinical studies.Therefore, a prospective, open-label, multicenter clinical study of recombinant human erythropoietin in the treatment of anemia in patients with lymphoma is planned to analyze the efficacy and safety of recombinant human erythropoietin in patients with lymphoma and anemia, so as to determine the clinical benefits of recombinant human erythropoietin in patients with lymphoma and anemia.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma; Anemia
• Intervention / Treatment: Drug: recombinant human erythropoietin

Detailed Description

Anemia is a common complication of malignant lymphoma.Approximately 30-40% of lymphoma patients develop anemia before chemotherapy begins [1].Common clinical manifestations of anemia include fatigue, weakness, dizziness, headache, shortness of breath, depression and other symptoms.Lymphoma anemia has a complex etiology, including chronic anemia (ACD), autoimmune hemolytic anemia (AIHA), bone marrow infiltration, malnutrition, and blood loss [2].

The incidence and prevalence of anemia are positively correlated with the severity of the disease and the chemotherapy cycle.A multi-center survey of anemia in patients with lymphoma in Shanghai published in 2020 included 501 patients, and the results showed that the incidence of anemia in patients with lymphoma was 35.5%;The prevalence of anemia was 62.7 percent during the entire 6-month follow-up period.Among the newly treated patients, the incidence of anemia was significantly higher in patients with Ann Arbor staging from Ⅲ to normal (P < 0.001), indicating that the incidence of anemia was related to the severity of the disease.In addition, chemotherapy is also a key factor in the development of anemia during the course of the disease.In this Shanghai survey, 267 newly treated lymphoma patients receiving chemotherapy increased the rate of newly diagnosed anaemia from 6.82% in the first course of chemotherapy to 43.18% in the fourth course of chemotherapy and above [3].The results of the European Anemia Survey of 15,367 cancer patients (ECAS) conducted in 2004 also showed a high incidence of anemia in lymphoma patients (2 260 lymphoma patients, 52.5%) [4], and the cumulative incidence of anemia in patients increased with the increase of chemotherapy cycles [5].

Anemia can reduce the quality of life of tumor patients, affect the therapeutic effect, and shorten the survival period of patients [6].A number of studies have shown that anemia is an independent risk factor affecting the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) [7, 8].Compared with patients with Hb≥10 g/dL, those with Hb≥10 g/dL were more likely to have bone marrow involvement before treatment.Patients with lymphoma at 10 g/dL showed a lower event-free and disease-free survival.R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) was also an independent predictor of disease recurrence and an independent predictor of International Prognostic Index (IPI) 6 months after chemotherapy [7].After 3-4 courses of chemotherapy, the efficacy of newly treated lymphoma patients was evaluated, and it was found that the efficacy gradually deteriorated with the increase of anemia level [3].Another domestic study found that among 12L patients treated with R-CHOP regimen, 77 patients had grade 2 anemia or above (Hb < 10g/ dL, 63.6%), and the analysis results of the relationship between different Hb grades and overall survival showed that the greater the degree of anemia, the lower the overall survival rate of patients [9].

Although patients with lymphoma have a higher incidence of anemia, most patients do not receive prompt treatment.ECAS survey showed that anemia treatment rate of lymphoma patients was low, only 47.4%[4].For patients with tumor-associated anemia, treatment includes red blood cell transfusions, erythropoiesis stimulants (ESAs), and iron.Before the emergence of ESAs, blood transfusion was the main treatment.Although blood transfusions can quickly raise Hb levels, there are risks associated with allergies, viral infection, immunosuppression and iron overload.So the only Hb<Blood transfusion should be considered at 60 g/L or when hypoxia is urgently corrected clinically.ECAS survey showed that recombinant human erythropoietin (rHuEPO) was the main treatment for cancer anemia, but the treatment rate was low (17.4%) [4].Previous studies have confirmed that rHuEPO has achieved positive efficacy in the treatment of anemia caused by solid tumors and hematologic tumors.A 2008 study showed that the response rate of 33 NHL patients receiving chemotherapy treated with rHuEPO was 84.8%, and the earlier the treatment of rHuEPO, the higher the response rate [10].Glossmann J P et al. investigated the effects of rHuEPO on Hb level, blood transfusion volume and quality of life in patients with recurrent lymphoma, and found that while rHuEPO increased Hb level, it reduced the need for blood transfusion and improved the quality of life of patients [11].However, in recent years, concerns about the safety of rHuEPO in cancer patients have limited its clinical application.In recent years, large meta-analyses and randomized controlled studies have not shown that ESAs promote tumor progression [12-15].The "Management of Anemia and Iron Deficiency in Cancer Patients: ESMO Clinical Practice Guidelines" published by the European Society of Physicians of Oncology (ESMO) in 2018 also clearly pointed out that the standardized use of ESAS would not promote the progression or recurrence of cancer disease [16].Therefore, the appropriate use of rHuEPO in lymphoma patients undergoing chemotherapy can provide clinical benefits such as reduced need for blood transfusion and improved quality of life without excessive safety concerns.

In view of the high incidence of lymphoma anemia and greater clinical harm.However, it has not yet attracted enough clinical attention, and domestic rHuEPO (trade name: Ebio).Shenyang Sansheng Pharmaceutical Co., Ltd.) for lymphoma and anemia patients are less clinical studies.Therefore, a prospective, open-label, multicenter clinical study of recombinant human erythropoietin in the treatment of anemia in patients with lymphoma is planned to analyze the efficacy and safety of recombinant human erythropoietin in patients with lymphoma and anemia, so as to determine the clinical benefits of recombinant human erythropoietin in patients with lymphoma and anemia.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: wenbin qian; Phone Number: +86 13605801032; Email: qwb@zju.edu.cn
• Study Contact Backup: Name: xibin xiao; Phone Number: +86 13858015535; Email: xiaoxibinzju@zju.edu.cn

Study Locations

• China
  • Hanzhou, China
    • Recruiting
    • 2 nd Affiliated Hospital, School of Medicine, Zhejiang University, China
    • Contact: xibin xiao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histopathological diagnosis: lymphoma;
2. Age 14 to 65, no gender limitation;
3. ECOG physical condition score was 0~3;
4. Life expectancy >6 months;
5. did not receive recombinant human erythropoietin treatment within 30 days before the first day;
6. Complete liver and kidney function (creatinine ≦1.5*ULN, BUN≦1.5*ULN, ALT≦2*ULN, AST≦2*ULN, total bilirubin ≦1.5*ULN;ULN: upper limit of normal value);
7. Willing to sign the informed consent, can understand and abide by the requirements of the study.

Exclusion Criteria:

1. Active infections requiring intravenous antibiotic treatment and any active malignancies (except lymphomas);
2. Grade III or IV heart failure, uncontrolled hypertension or hypotension, and associated risk or event of thromboembolism;
3. Severe hepatic and renal insufficiency;
4. Patients who have received radiotherapy or chemotherapy for other tumors (except lymphoma) within 6 months;
5. other anemia diseases (such as aplastic anemia, thalassemia, myelodysplastic syndrome, etc.);
6. Inability to understand and follow the study protocol or inability to sign the informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin response rate of subjects during treatment.	A hemoglobin response was defined as an increase in hemoglobin levels of ≥ 1.0 g/dL from baseline during 2 or more consecutive assessments (2 weeks apart) without red blood cell infusion.	up to 20weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time of the first hemoglobin response	The time of the first hemoglobin response	up to 20weeks

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Zhejiang Cancer Hospital; First People's Hospital of Hangzhou; Ningbo Medical Center Lihuili Hospital; Second Affiliated Hospital of Wenzhou Medical University; First Affiliated Hospital of Wenzhou Medical University; Wenzhou Central Hospital; Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University; The First Affiliated Hospital of Zhejiang Chinese Medical University; Zhejiang Provincial Tongde Hospital; First Affiliated Hospital of Jiaxing University
• Investigators: Principal Investigator: wenbin qian, 2 nd Affiliated Hospital, School of Medicine, Zhejiang University, China

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2021
• Primary Completion (ANTICIPATED): February 14, 2023
• Study Completion (ANTICIPATED): April 1, 2023

Study Registration Dates

• First Submitted: May 31, 2021
• First Submitted That Met QC Criteria: May 31, 2021
• First Posted (ACTUAL): June 2, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 11, 2021
• Last Update Submitted That Met QC Criteria: August 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: lymphoma; anemia; recombinant human erythropoietin
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Lymphoma; Anemia; Hematinics; Epoetin Alfa
• Other Study ID Numbers: 2021-0135

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: share the dates when published
• IPD Sharing Time Frame: up to ten years
• IPD Sharing Access Criteria: by pubmed
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No