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

Phase 3

• Conditions: Lymphoma; Neutropenia
• Interventions: Drug: Pegfilgrastim

• Registration Number: NCT02238873
• Lead Sponsor: Rabin Medical Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-09-08
• Study First Submitted QC: 2014-09-11
• Study First Posted: 2014-09-12
• Status Verified: 2014-10
• Study Start: 2014-10
• Last Update Submitted: 2014-10-01
• Last Update Posted: 2014-10-02
• Primary Completion: 2018-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 300

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pegfilgrastim +1	Pegfilgrastim	Pegfilgrastim will be given 24 hours (day +1) after completion of salvage chemotherapy
Pegfilgrastim +3	Pegfilgrastim	Pegfilgrastim will be given 72 hours (day +3) after completion of salvage chemotherapy

Primary Outcome Measures

Name	Time	Method
Neutrophil count <500/ mcL	day 8 to 10	Number of participants with neutrophil count below 500 /mcL
Febrile neutropenia	30 days	Number of participants with fever and neutropenia

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Rabin Medical Center; 🇮🇱 Petah Tikva, Israel