A randomized, open-label, two-arm, multicenter, comparatiVe study on efficacy and safety of lipegfilgrastim (Lonquex, TEVA) in comparison to pegfilgrastim (Neulasta®, Amgen) in elderly patients with aggressive B cell Non-HOdgkin lymphomas at hIgh risk for R-CHOP-21-inDuced neutropenia – AVOID Neutropenia

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2013-001284-23-IT
• Date of registration: 10/02/2014
• Prospective Registration: Yes
• Primary sponsor: Merckle GmbH
• Public title: A randomized, open-label, two-arm, multicenter, comparatiVe study on efficacy and safety of lipegfilgrastim (Lonquex, TEVA) in comparison to pegfilgrastim (Neulasta®, Amgen) in elderly patients with aggressive B cell Non-HOdgkin lymphomas at hIgh risk for R-CHOP-21-inDuced neutropenia – AVOID Neutropenia
• Scientific title: A randomized, phase IIIB, open-label, two-arm, multicenter, comparatiVe study on efficacy and safety of lipegfilgrastim (Lonquex, TEVA) in comparison to pegfilgrastim (Neulasta®, Amgen) in elderly patients with aggressive B cell Non-HOdgkin lymphomas at hIgh risk for R-CHOP-21-inDuced neutropenia – AVOID Neutropenia - AVOID Neutropenia
• Date of first enrolment: 16/05/2014
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001284-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Italy, Spain

Contacts

• Name: Clinical Operations
• Affiliation: iOMEDICO AG

• Name: Clinical Operations
• Affiliation: iOMEDICO AG

Key inclusion & exclusion criteria

Inclusion criteria:
a. Signed and dated Independent Ethics Committee (IEC)-approved written informed consent
b. Age =65 years and =85 years
c. Histological documentation of aggressive B cell NHL
d. Planned to receive systemic anticancer therapy with at least 6 cycles of R-CHOP-21, according to local standards
e. ECOG score =2
f. Life expectancy of at least 3 months
g. Adequate bone marrow, renal and hepatic function as evidenced by the following within 14 days before start of chemotherapy:
-absolute neutrophil count (ANC) =1.5 x 109/L
-platelets =100 x 109/L
-hemoglobin =9.0 g/dL
-serum creatinine =1.5 x upper limit of the normal range (ULN) OR glomerular filtration rate (GFR) =30 mL/minute/1.73 m2
-Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 x ULN; bilirubin =1.5 x ULN; alkaline phosphatase limit =2.5 x ULN
h. The patient is capable of understanding and complying with parameters as outlined in the protocol
i. 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. Acceptable methods of contraception include intrauterine device (IUD), steroidal contraceptive (oral, implanted, transdermal, or injected), barrier method with spermicide, abstinence, and partner vasectomy.
j. 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 drug because of the possible effects on spermatogenesis). Acceptable methods of
contraception include abstinence, female partner's use of an acceptable method of
contraception (described above), or if female partner is surgically sterile or 2
years post-menopausal. In addition, male patients may not donate sperm for the
duration of the study and for 90 days after taking study drug.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion criteria:
a. Participation in a clinical study within 30 days before randomization
b. 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.
c. The patient is a pregnant or lactating woman. (Any woman becoming pregnant during
the study will be withdrawn from the study.)
d. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of chemotherapy.
e. Active cardiac disease including any of the following:
-Congestive heart failure >New York Heart Association (NYHA) class 2.
-Unstable angina, new-onset angina, myocardial infarction less than 6 months before start of chemotherapy.
-Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
-Uncontrolled hypertension.
f. 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.
g. Ongoing infection, known history of human immunodeficiency virus (HIV) infection, tuberculosis, or chronic hepatitis B or C.
h. Patients with evidence or history of bleeding diathesis.
i. Non-healing wound, ulcer or bone fracture.
j. Renal failure requiring hemo- or peritoneal dialysis.
k. Any conditions that may interfere with the patient’s participation in the study or evaluation of the study results.
l. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
m. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.
n. Treatment with lithium at screening or planned during the study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

The study population includes patients with aggressive B cell Non-Hodgkin Lymphoma (NHL) planned to receive systemic anti-cancer therapy with at least 6 cycles of R-CHOP-21, according to local standards.
MedDRA version: 16.1 Level: LLT Classification code 10066481 Term: Hematological malignancy System Organ Class: 100000004864

Intervention(s)

Trade Name: Lonquex
Product Name: Lonquex
Product Code: XM22
Pharmaceutical Form: Solution for injection
INN or Proposed INN: lipegfilgrastim
CAS Number: 1117844-87-7
Current Sponsor code: XM22
Other descriptive name: GlycoPEGylated r-metHuG-CSF
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Neulasta®
Product Name: pegfilgrastim
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEGFILGRASTIM
CAS Number: 208265-92-3
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: The primary objective of this study is to demonstrate non-inferiority of lipegfilgrastim (Lonquex, Teva) vs. pegfilgrastim (Neulasta®, Amgen) for the duration of severe neutropenia (DSN) in the first cycle of chemotherapy.

Primary end point(s): The primary endpoint for this study is the duration of severe neutropenia in days in the first cycle of chemotherapy.

Secondary Objective: -To compare efficacy of lipegfilgrastim and pegfilgrastim in elderly patients with B cell NHL receiving chemotherapy with R-CHOP-21 throughout the study.
-To compare safety and tolerability of lipegfilgrastim and pegfilgrastim in elderly patients with B cell NHL receiving chemotherapy with R-CHOP-21 throughout the study.
-To assess incidence and severity of infections throughout the study.
-To compare effect of lipegfilgrastim and pegfilgrastim treatment on quality of life.
-To further characterize exposure-response relationships for lipegfilgrastim.
-To further characterize the immunogenicity of lipegfilgrastim.

Timepoint(s) of evaluation of this end point: days 1, 3, 5, 8, 10, 12, 15

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Daily temperature measurement; ANC assessment days 1, 3, 5, 8, 10, 12, 15 in cycle one and days 1, 8, 15 in all other cycles

Secondary end point(s): - Incidence of febrile neutropenia (FN) by cycle and across all cycles
- Incidence of severe/very severe neutropenia in Cycle 1
- Depth of ANC nadir in Cycle 1
- Proportion of patients with severe neutropenia lasting <1 day, <2 days, <3 days, or =3 days in Cycle 1
- Time to ANC recovery in first treatment cycle
- Incidence and severity of infections.
- Time in hospital and time in intensive care unit due to all causes and due to FN or connected
infections.
- Incidence of hospitalizations by cycle due to FN.
- Incidence of treatment with IV and oral antibiotics due to FN or connected infections.
- Percentage of actually delivered vs. scheduled cumulative chemotherapy dose.
- Proportion of patients with chemotherapy doses reduced, omitted, or delayed.

Secondary ID(s)

2013-001284-23-DE

XM22-ONC-305

Source(s) of Monetary Support

Merckle GmbH