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

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

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.

Study Overview

• Status: Unknown
• Conditions: Lymphoma; Neutropenia
• Intervention / Treatment: Drug: Pegfilgrastim

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Pegfilgrastim +1; Pegfilgrastim will be given 24 hours (day +1) after completion of salvage chemotherapy	Drug: Pegfilgrastim; Other Names: Neulastim
EXPERIMENTAL: Pegfilgrastim +3; Pegfilgrastim will be given 72 hours (day +3) after completion of salvage chemotherapy	Drug: Pegfilgrastim; Other Names: Neulastim

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Collaborators: Tel-Aviv Sourasky Medical Center; Soroka University Medical Center

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (ANTICIPATED): January 1, 2018

Study Registration Dates

• First Submitted: September 8, 2014
• First Submitted That Met QC Criteria: September 11, 2014
• First Posted (ESTIMATE): September 12, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): October 2, 2014
• Last Update Submitted That Met QC Criteria: October 1, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: lymphoma; neutropenia; pegfilgrastim
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Lymphoma; Neutropenia
• Other Study ID Numbers: PEGFIL