Clinical trial NCT02467868: Efficacy and Safety Study With MYL-1401H and Neulasta
Official title: Multicenter, Double-Blind, Randomized, Comparative Efficacy and Safety Study of MYL-1401H and European Sourced Neulasta® in Stage II/III Breast Cancer Patients Receiving Neoadjuvant or Adjuvant Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Neoplasms
Chemotherapy-Induced Febrile Neutropenia
Keywords: Pegfilgrastim
Granulocyte Colony Stimulating Factor (G-CSF)
Breast Cancer
Neutropenia
Lead sponsor: Viatris Inc.
Sponsor class: INDUSTRY
Collaborators: name: Mylan GmbH
First posted: 2015-06-10
Enrollment: 193
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Multicenter, Double-Blind, Randomized, Comparative Efficacy and Safety Study of MYL-1401H and Neulasta (Pegfilgrastim) in Stage II/III Breast Cancer Patients Receiving Neoadjuvant or Adjuvant Chemotherapy.

Detailed description: After successful screening, eligible patients will be randomly allocated to one of the two study arms, either receiving MYL-1401H or Neulasta.

Randomization is 2:1 to MYL-1401H or Neulasta, respectively.

Subjects will receive first of six cycles of background therapy (Docetaxel, Doxorubicin, Cyclophosphamide \[TAC\]) on day 1. Treatment with study drug (either MYL-1401H or Neulasta) is scheduled on Day 2 of each cycle, at least 24 hours after chemotherapy administration.

Duration of each cycle is 3 weeks.

Follow-up visit is scheduled 24 weeks after the first administration of study drug.

Eligibility criteria: Inclusion Criteria:

* Signed and dated written informed consent.
* Patients ≥18 years.
* Women of child-bearing potential must agree to use effective methods of birth control during the treatment period from the first dose of study drug until 6 months following the last dose of study drug.
* Newly diagnosed, pathologically confirmed breast cancer.
* Stage II or III breast cancer with adequate staging workup and adequate surgery if receiving adjuvant therapy.
* Patients planned/eligible to receive neoadjuvant or adjuvant treatment with (Docetaxel, Doxorubicin, Cyclophosphamide \[TAC\]) for their breast cancer.
* Cancer Chemotherapy and Radiotherapy naïve.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
* Absolute neutrophil count ≥ 1.5 × 109/L ; Platelet count ≥ 100 × 109/L ;
* Hemoglobin \> 10 g/dL without blood transfusions or cytokine support during the two weeks previous to the hemoglobin level.
* Adequate cardiac function (including left ventricular ejection fraction ≥ 50% as assessed by echocardiography) within 4 weeks prior to start of chemotherapy.
* Adequate renal function, i.e., creatinine \< 1.5 × upper limit of normal (ULN).

Other protocol specific inclusion/exclusion criteria may apply

Exclusion Criteria:

* Participation in a clinical trial in which they received an investigational drug within 28 days before randomization.
* Previous exposure to filgrastim, pegfilgrastim, lenograstim, lipegfilgrastim, or other filgrastim forms on the market or in clinical development.
* Received blood transfusions or erythroid growth factors within 2 weeks prior to first dose of chemotherapy.
* Known hypersensitivity to any drugs or excipients that patients will be receiving during the study.
* Known hypersensitivity to E. coli-derived products.
* Known fructose intolerance (related with sorbitol excipient).
* Underlying neuropathy of grade 2 or higher.
* Active infectious disease or any other medical condition which might put the patient at significant risk to tolerate 6 courses of TAC chemotherapy (e.g., recent myocardial infarction).
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 × Upper limit of normal (ULN), ALT and/or AST \> 1.5 × ULN with alkaline phosphatase (ALP) \> 2.5 × ULN; any bilirubin \> ULN.
* Treatment with systemically active antibiotics within 5 days before first dose of chemotherapy.
* Patients under treatment with lithium.
* Chronic use of oral corticosteroids.
* Splenomegaly of unknown origin by physical examination and/or computerized tomography scan or ultrasound and any condition which can cause splenomegaly, e.g., thalassemia, glandular fever, hemolytic anemias, and malaria.
* Myeloproliferative or myelodysplastic disorders, sickle cell disorders, and any illness or condition that in the opinion of the investigator may affect the safety of the patient or the evaluation of any study endpoint.
* Increase potential risk of Adult Respiratory Distress Syndrome.
* Pregnant or nursing women.
* Patients known to be seropositive for human immunodeficiency virus (HIV), or who have had an acquired immunodeficiency syndrome (AIDS) defining illness or a known immunodeficiency disorder.
* A known active abuse of drugs or alcohol should preclude patient participation and evaluation in the study.
* Any known psychiatric conditions.
* Any disease or physical condition that may not allow for the adequate performance of study assessments, such as lack of access to patient's domiciliary, and distance of patient's domiciliary from clinic site.

Primary outcomes:
measure: Mean Duration of Severe Neutropenia (DSN), defined as consecutive days with absolute neutrophil count (ANC) < 0.5 × 109/L
timeFrame: Cycle 1 of chemotherapy (approx 21 days)
Secondary outcomes:
measure: The rate of febrile neutropenia (FN)
timeFrame: Week 24 (End of the study)
Other outcomes:
measure: Incidence, nature, and severity of adverse events (AEs)
timeFrame: Week 24
measure: Presence of antibodies against MYL-1401H and Pegfilgrastim
timeFrame: Week 24
Locations:
city: Plovdiv
country: Bulgaria
facility: Mylan Investigational Site 3502
city: Plovdiv
country: Bulgaria
facility: Mylan Investigational Site 3506
city: Plovdiv
country: Bulgaria
facility: Mylan Investigational Site 3507
city: Sofia
country: Bulgaria
facility: Mylan Investigational Site 3503
city: Sofia
country: Bulgaria
facility: Mylan Investigational Site 3505
city: Tarnovo
country: Bulgaria
facility: Mylan Investigational SIte 3501
city: Varna
country: Bulgaria
facility: Mylan Investigational Site 3504
city: Tbilisi
country: Georgia
facility: Mylan Investigational Site 9901
city: Tbilisi
country: Georgia
facility: Mylan Investigational Site 9902
city: Tbilisi
country: Georgia
facility: Mylan Investigational Site 9903
city: Tbilisi
country: Georgia
facility: Mylan Investigational Site 9904
city: Tbilisi
country: Georgia
facility: Mylan Investigational Site 9905
city: Tbilisi
country: Georgia
facility: Mylan Investigational Site 9906
city: Tbilisi
country: Georgia
facility: Mylan Investigational Site 9907
city: Bonn
country: Germany
facility: Mylan Investigational site 4905
city: Budapest
country: Hungary
facility: Mylan Investigational Site 3604
city: Budapest
country: Hungary
facility: Mylan Investigational SIte 3606
city: Budapest
country: Hungary
facility: Mylan Investigational Site 3607
city: Debrecen
country: Hungary
facility: Mylan Investigational Site 3609
city: Gyula
country: Hungary
facility: Mylan Investigational Site 3601
city: Nyiregyhaza
country: Hungary
facility: Mylan Investigational SIte 3605
city: Szombathely
country: Hungary
facility: Mylan Investigational Site 3603
city: Zalaegerszeg
country: Hungary
facility: Mylan Investigational Site 3602
city: Bydgoszcz
country: Poland
facility: Mylan Investigational site 4802
city: Koscierzyna
country: Poland
facility: Mylan Investigational Site 4805
city: Krakow
country: Poland
facility: Mylan Investigational SIte 4804
city: Chernivtsi
country: Ukraine
facility: Mylan Investigational SIte 3804
city: Dniepropetrovsk
country: Ukraine
facility: Mylan Investigational site 3801
city: Dniepropetrovsk
country: Ukraine
facility: Mylan Investigational Site 3805
city: Kharkiv
country: Ukraine
facility: Mylan Investigational Site 3808
city: Kyiv
country: Ukraine
facility: Mylan Investigational Site 3810
city: Lutsk
country: Ukraine
facility: Mylan Investigatational Site 3802
city: Lviv
country: Ukraine
facility: Mylan Investigational SIte 3807
city: Odesa
country: Ukraine
facility: Mylan Investigational SIte 3803
city: Sumy
country: Ukraine
facility: Mylan Investigational Site 3809
city: Uzhgorod
country: Ukraine
facility: Mylan Investigational Site 3806
Study officials:
affiliation: Mylan GmbH
name: Rasmus Rojkjaer, MD
role: STUDY_CHAIR
References:
citation: Waller CF, Ranganna GM, Pennella EJ, Blakeley C, Bronchud MH, Mattano LA Jr, Berzoy O, Voitko N, Shparyk Y, Lytvyn I, Rusyn A, Popov V, Lang I, Beckmann K, Sharma R, Baczkowski M, Kothekar M, Barve A. Randomized phase 3 efficacy and safety trial of proposed pegfilgrastim biosimilar MYL-1401H in the prophylactic treatment of chemotherapy-induced neutropenia. Ann Hematol. 2019 May;98(5):1217-1224. doi: 10.1007/s00277-019-03639-5. Epub 2019 Mar 1.