Pegfilgrastim on Day +3 Compared to Day +1 After Salvage Chemotherapy for Patients With Refractory or Relapsed Aggressive Lymphoma

Study Overview
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Brief Summary
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Granulocyte colony stimulating factors (GCSFs) stimulate the level of white blood cells, specifically neutrophils. GCSF support for patients receiving chemotherapy was shown to decrease the rate of fever during low neutrophil count (neutropenia), and in some cancer types may decrease mortality. Pegfilgrastim is a pegylated form of the GCSF named filgrastim. Pegfilgrastim is used to stimulate bone marrow to produce more neutrophils to fight infection in patients undergoing chemotherapy. It has a much longer half-life than the parent filgrastim. It is removed from the body within the neutrophils. According to the American Society of Clinical Oncology 2006 guidelines pegfilgrastim should be given 24 hours after the completion of chemotherapy i.e.before neutrophil count starts to drop. Therefore it is cleared before and after neutropenia. Comparative low quality studies suggest that deferring pegfilgrastim delivery until neutrophil counts start dropping may result in improved its efficacy. This was further tested in a few small randomized controlled trials (high quality studies, considered the gold standard of studies) in different settings (including first chemotherapy for lymphoma, and solid cancer) with inconsistent results. Pegfilgrastim (given 24 hours after completion of chemotherapy) is a standard part of any salvage chemotherapy for patient with refractory or relapsed aggressive lymphoma. The investigators plan a randomized controlled trial comparing the efficacy of pegfilgrastim given 72 hours (day +3) vs. 24 hours (day +1) after completion of salvage chemotherapy in patients with refractory or relapsed aggressive lymphoma. The investigators will evaluate whether that change of pegfilgrastim schedule affects the risk of fever during neutropenia, neutrophil count, length of hospitalization, mortality, and safety.

Official Title
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Pegfilgrastim on Day +3 Compared to Day +1 for Patients With Refractory or Relapsed Aggressive Lymphoma Receiving Salvage Chemotherapy - a Randomized Controlled Trial

Conditions
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Lymphoma, Neutropenia

Intervention / Treatment
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* Drug: Pegfilgrastim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (age 18 years or above) Refractory or relapsed aggressive lymphoma, including Hodgkin's and non-Hodgkin's lymphoma Candidate for salvage chemotherapy. Salvage chemotherapy includes one of the following regimens: Ifosfamide, etoposide, vincristine (ICE), Cisplatin, cytarabine, and dexamethasone (DHAP), Etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP). Chemotherapy dose reduction will be allowed. Chemotherapy with or without immunotherapy Therapy in hospital or at the outpatient clinic Exclusion Criteria: Indolent lymphoma; we will exclude patients with transformed lymphoma. Treatment with GCSFs for the primary disease (e.g. aplastic anemia, MDS). Uncontrolled infection Pregnant women

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pegfilgrastim +1<br>Pegfilgrastim will be given 24 hours (day +1) after completion of salvage chemotherapy | Drug: Pegfilgrastim<br> <br> * Other names: Neulastim;|
| Experimental: Pegfilgrastim +3<br>Pegfilgrastim will be given 72 hours (day +3) after completion of salvage chemotherapy | Drug: Pegfilgrastim<br> <br> * Other names: Neulastim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Febrile neutropenia | Number of participants with fever and neutropenia | 30 days | 
| Neutrophil count <500/ mcL | Number of participants with neutrophil count below 500 /mcL | day 8 to 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Number of participants who died by day 30 | 30 days | 
| Neutrophil count <100/ mcL | Number of patients with neutrophil count below 100/ mcL | day 8 to 10 | 
| Number of febrile days | a febrile day defined by at least one documented temperature measurement >38ºC | 30 days | 
| Development of clinically documented infections (CDI), microbiologically-documented infections (MDI) and clinically-significant bloodstream infections (BSI), not present at the time of randomization | Number of participants with CDI, MCI or BSI. CDI, MDI and BSI will be defined in accordance with the CDC surveillance definitions for healthcare-associated infections | 30 days | 
| Hospitalization | Number of hospitalization days of each participant (excluding days of hospitalization for chemotherapy) | 30 days | 
| Adverse events | ECOG common toxicity criteria grading Number of patients with an adverse event (AE). Number of patients with grade 3-4 AE | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neutropenia, lymphoma, pegfilgrastim