A comparatiVe Study on Efficacy and Safety of Lipegfilgrastim in Comparison to Pegfilgrastim in Elderly Patients With Aggressive B Cell Non-HOdgkin Lymphomas at hIgh Risk for R-CHOP-21-inDuced Neutropenia

Study Overview
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Brief Summary
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The primary objective of the study is to demonstrate non-inferiority of lipegfilgrastim to pegfilgrastim for the duration of severe neutropenia in the first cycle of chemotherapy.

Official Title
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A Randomized, Phase IIIB, Open-label, Two-arm, Multicenter, comparatiVe Study on Efficacy and Safety of Lipegfilgrastim (Lonquex, TEVA) in Comparison to Pegfilgrastim (Neulasta(R), Amgen) in Elderly Patients With Aggressive B Cell Non-HOdgkin Lymphomas at hIgh Risk for R-CHOP-21-inDuced Neutropenia - AVOID Neutropenia

Conditions
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Aggressive B Cell Non-Hodgkin Lymphomas at High Risk for R-CHOP-21-induced Neutropenia

Intervention / Treatment
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* Drug: lipegfilgrastim
* Drug: pegfilgrastim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated Independent Ethics Committee (IEC)-approved written informed consent Age ≥65 years and ≤85 years Histological documentation of aggressive B cell NHL Planned to receive systemic anticancer therapy with at least 6 cycles of R-CHOP-21, according to local standards ECOG score ≤2 Life expectancy of at least 3 months Adequate bone marrow, renal and hepatic function within 14 days before start of chemotherapy The patient is capable of understanding and complying with parameters as outlined in the protocol Women of childbearing potential (not surgically sterile or 2 years postmenopausal) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the treatment and for 30 days after discontinuation of study drug. The patient, if a man, is surgically sterile, or, if capable of producing offspring, is currently using an approved method of birth control and agrees to continued use of this method for the duration of the treatment (and for 90 days after taking the last dose of study Other Criteria apply, please contact the investigator for more information Exclusion Criteria: Participation in a clinical study within 30 days before randomization Any chemotherapy within the last 3 months before start of chemotherapy. A prephase to reduce tumor burden prior to start of R-CHOP is allowed. The patient is a pregnant or lactating woman. (Any woman becoming pregnant during the study will be withdrawn from the study.) Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of chemotherapy. Active cardiac disease Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of chemotherapy. Ongoing infection, known history of human immunodeficiency virus (HIV) infection, tuberculosis, or chronic hepatitis B or C. Patients with evidence or history of bleeding diathesis. Non-healing wound, ulcer or bone fracture. Renal failure requiring hemo- or peritoneal dialysis. Any conditions that may interfere with the patient's participation in the study or evaluation of the study results. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study. Treatment with lithium at screening or planned during the study. Other Criteria apply, please contact the investigator for more information

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lipegfilgrastim.<br>subcutaneous (SC) injection of 6 mg lipegfilgrastim | Drug: lipegfilgrastim<br>* 6 mg<br>* Other names: XM22;|
| Active Comparator: pegfilgrastim<br>SC injection of 6 mg pegfilgrastim | Drug: pegfilgrastim<br>* 6 mg<br>* Other names: Neulasta®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of severe neutropenia (DSN) ANC <0.5 * 10^9/L | Grade 4 neutropenia measured in days | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of febrile neutropenia (FN) (strict definition) | Body temperature of >38.5°C for at least one hour and ANC<1*10^9/L | 18 weeks | 
| Incidence of FN | A single temperature of ≥38.3°C or ≥38.0°C for at least one hour and ANC <1 * 10^9/L | 18 weeks | 
| Incidence of very severe neutropenia | The occurrence of at least one incidence of ANC <0.1 * 10*9/L | 3 weeks | 
| Incidence of infections | Incidence and severity of infections | 18 weeks | 
| Time to ANC recovery | The time in days from start of chemotherapy administration until the ANC increases to ≥1.0 x 109/L, ≥1.5 x 109/L, and ≥2.0 x 109/L after the expected nadir | 3 weeks | 
| Summary of participants with adverse events |  | 9 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neutropenia, NHL, Non-Hodgkin lymphomas, R-CHOP-21