PEG-rhG-CSF in Patients With Non-Hodgkin Lymphoma Receiving Chemotherapy to Prevent Neutropenia

Lymphoma,Non-Hodgkin Clinical Trial

Official title:

PEG-rhG-CSF in Patients With Non-Hodgkin Lymphoma Receiving Chemotherapy to Prevent Neutropenia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02996617
• Other study ID #: ShandongPH02
• Status: Recruiting
• Phase: Phase 4
• First received: November 19, 2016
• Last updated: December 15, 2016
• Start date: November 2016
• Est. completion date: December 2018

Study information

• Verified date: December 2016
• Source: Shandong Provincial Hospital
• Contact: xin wang, MD, PHD
• Phone: 86-531-68778331
• Email: xinw007[@]126.com
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Neutropenia is one of the most frequent adverse effects of chemotherapy, and the main factor to limit the dosage and the continuation of chemotherapy. The PEG-rhG-CSF has increased plasma half-life, and prolonged efficacy in compare with rhG-CSF. The purpose of this study is to determine the safety and effectiveness of PEG-rhG-CSF in preventing neutropenia following chemotherapy in patients with non-Hodgkin lymphoma.

Description:

Neutropenia is a common clinical complication of chemotherapy in cancer patients. It is an important factor that delays the course of standard treatments in patients. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is an effective drug for the treatment of chemotherapy-induced neutropenia. However, for patients with neutropenia, multiple rhG-CSF treatments are usually required. This is likely to extend the antitumor treatment period and increase physical and mental stress in patients. Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) is rhG-CSF chemically modified by a single methoxy polyethylene glycol group; it is able to alleviate neutropenia with a single dose. The aim of the present study was to determine the safety and effectiveness of preventive treatment with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) on concurrent chemotherapy-induced neutropenia and to provide a rational basis for its clinical application. Therefore, the investigators designed the multi-center, open-label,randomized controlled clinical study and aimed to compare the efficacy and safety between PEG-rhG-CSF and rhG-CSF in non-Hodgkin lymphoma receiving chemotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Investigator diagnosis of non-Hodgkin lymphoma(Highly invasive lymphoma/Burkitt lymphoma were excluded)

• Age 18 to 80 years

• ECOG performance status = 2

• receive multi-cycle Chemotherapy naive

• grade 3/4 neutropenia occurred in the patient's first cycle chemotherapy or the risk of neutropenia >20% without rhG-CSF support

• Expected survival time=3 months; cNormal bone marrow function(absolute neutrophil count =1.5 × 109/L; platelet count = 80 × 109/L)

• Liver function: transaminase=2.5× upper limit of normal value,bilirubin=2.5×upper limit of normal value; serum creatinine=2×upper limit of normal value;

Exclusion Criteria:

• Patients with severe complications or severe infection;

• Invasion of central nervous system;

• Patients with severe visceral organ dysfunction, heart block, myocardial infarction within 6 months;

• Prior bone marrow stem cell or organ transplantation

• patients with severe allergic constitution, or those who are allergic to Escherichia coli products; 5. Patients participate in other clinical studies within 4 weeks;

• Pregnancy, lactation

• Other patients who are not suitable for the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Lymphoma,Non-Hodgkin
• Neutropenia

Intervention

Drug:
• rhG-CSF regimen
Patients weren't preventive use of rhG-CSF.If their WBC=1×10^ 9/L,they were administered rhG-CSF:5ug/kg/day until their WBC=4×10^ 9/L.Chemotherapy regimen: CHOP: Epirubicin:70 mg/m2 , Cyclophosphamide:750 mg/m2, Vincristine: 1.4 mg/m2 , Prednison:100mg/d; CHOPE: Epirubicin:70 mg/m2, Cyclophosphamide:750 mg/m2,Vincristine: 1.4 mg/m2,Prednison:100mg/d,Etoposide: 100 mg/(m2•d);EPOCH:etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin;Hyper-CVAD(A):hyperfractionated cyclophosphamide, vincristine,doxorubicin, dexamethasone, cytarabine and methotrexate;GemOx-R:Gemcitabine, Oxaliplatin;GDP:gemcitabine, dexamethasone, and cisplatin
• Pegylated rhG-CSF regimen
Patients were administered pegylated rhG-CSF 6mg(weight=45Kg)or 3mg(weight=45Kg)once 24 hours after the end of chemotherapy drugs of every chemotherapy cycle.Chemotherapy regimen: CHOP: Epirubicin:70 mg/m2 , Cyclophosphamide:750 mg/m2, Vincristine: 1.4 mg/m2 , Prednison:100mg/d; CHOPE: Epirubicin:70 mg/m2, Cyclophosphamide:750 mg/m2,Vincristine: 1.4 mg/m2,Prednison:100mg/d,Etoposide: 100 mg/(m2•d);EPOCH:etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin;Hyper-CVAD(A):hyperfractionated cyclophosphamide, vincristine,doxorubicin, dexamethasone, cytarabine and methotrexate;GemOx-R:Gemcitabine, Oxaliplatin;GDP:gemcitabine, dexamethasone, and cisplatin

Locations

Country	Name	City	State
China	Department of Hematology, Provincial Hospital Affiliated to Shandong University	Jin'an	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Shandong Provincial Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

Green MD, Koelbl H, Baselga J, Galid A, Guillem V, Gascon P, Siena S, Lalisang RI, Samonigg H, Clemens MR, Zani V, Liang BC, Renwick J, Piccart MJ; International Pegfilgrastim 749 Study Group.. A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol. 2003 Jan;14(1):29-35. — View Citation

Hadji P, Kostev K, Schröder-Bernhardi D, Ziller V. Cost comparison of outpatient treatment with granulocyte colony-stimulating factors (G-CSF) in Germany. Int J Clin Pharmacol Ther. 2012 Apr;50(4):281-9. Erratum in: Int J Clin Pharmacol Ther. 2012 Jul;50(7):532. — View Citation

Holmes FA, Jones SE, O'Shaughnessy J, Vukelja S, George T, Savin M, Richards D, Glaspy J, Meza L, Cohen G, Dhami M, Budman DR, Hackett J, Brassard M, Yang BB, Liang BC. Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann Oncol. 2002 Jun;13(6):903-9. — View Citation

Johnston E, Crawford J, Blackwell S, Bjurstrom T, Lockbaum P, Roskos L, Yang BB, Gardner S, Miller-Messana MA, Shoemaker D, Garst J, Schwab G. Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy. J Clin Oncol. 2000 Jul;18(13):2522-8. — View Citation

Molineux G. Pegylation: engineering improved pharmaceuticals for enhanced therapy. Cancer Treat Rev. 2002 Apr;28 Suppl A:13-6. Review. — View Citation

Shi YK, Chen Q, Zhu YZ, He XH, Wang HQ, Jiang ZF, Chang JH, Liu YP, Wang AL, Luo DY, Zhang Y, Ke XY, Li WL, Zhang WJ, Wang XW, Zhang YP, Wang JM, Liu XQ. Pegylated filgrastim is comparable with filgrastim as support for commonly used chemotherapy regimens: a multicenter, randomized, crossover phase 3 study. Anticancer Drugs. 2013 Jul;24(6):641-7. doi: 10.1097/CAD.0b013e3283610b5d. — View Citation

Wen TJ, Wen YW, Chien CR, Chiang SC, Hsu WW, Shen LJ, Hsiao FY. Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis in chemotherapy-induced febrile neutropenia among breast cancer and Non-Hodgkin's lymphoma patients under Taiwan's national health insurance system. J Eval Clin Pract. 2016 Aug 4. doi: 10.1111/jep.12597. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of grade 3/4 neutropenia(neutrophils=1×10^ 9/L) in every cycle	Proportion of patients grade 3/4 neutropenia(neutrophils=1×10^ 9/L)	through the study completion,an average of 4 months	Yes
Secondary	Rate of the chemotherapy delay	Proportion of chemotherapy delay(>7 days) caused by neutropenia	through the study completion,an average of 4 months	Yes
Secondary	Rate of the febrile neutropenia in every cycle	Proportion of febrile caused by neutropenia	through the study completion,an average of 4 months	Yes