Back to resultsEfficacy and Safety Phase IIa Study of Myelo001 in Chemotherapy-Induced Neutropenia (MyeloConcept)
Primary Purpose
Chemotherapy-Induced Neutropenia, Myelosuppression, Breast Cancer
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Myelo001
Placebo
Sponsored by
About this trial
This is an interventional supportive care trial for Chemotherapy-Induced Neutropenia focused on measuring Chemotherapy, Chemotherapy-induced Neutropenia, Supportive Care, Myelosuppression, CIN
Eligibility Criteria
Inclusion Criteria:
- Female patient of any racial origin having fulfilled her 18th birthday on Visit 1 (Screening)
- Histologically confirmed invasive breast cancer scheduled for neoadjuvant or adjuvant chemotherapy (patient with primary wound healing ([R0])
- Already selected for neoadjuvant or adjuvant standard of care EC regimen (Epirubicin 90 mg/m2 BSA (body surface area) + Cyclophosphamide 600 mg/m2 BSA q21d (every 21 days)) (with or without treatment with taxanes afterwards)
- Risk of chemotherapy-induced Febrile Neutropenia ≤20% according to ASCO Guidelines (2015)
- More than 5 days remaining before the planned initiation of the 1st chemotherapy cycle
- Performance status Grade 0-1 (ECOG)
- Echocardiography: No contraindication for the scheduled chemotherapy
Haematologic, laboratory and chemistry thresholds at baseline:
- Absolute neutrophil count (ANC) ≥2,000 cells/ mm3 (≥2.0 x 10/L)
- Platelet count ≥100,000/mm3 (≥100 x 10exp9/L)
- Haemoglobin ≥10 g/dL
- Total bilirubin <1.5 x, AST, ALT <2.5 x upper limit of normal (ULN)
- Serum creatinine <2.0 mg/dL
- Able to read, understand and willing to sign the informed consent form
- Able to undergo the investigations and to follow the Visit schedule
Exclusion Criteria:
- Suspected allergy to Myelo001 or its excipients
- Prior chemotherapy
- Prior or concomitant treatment with radiotherapy
- Currently on or scheduled for other immunomodulatory or immunosuppressive therapies (e.g. TNF inhibitors) during the first chemotherapy cycle
- Currently on or scheduled for other immunostimulatory or hematopoietic active therapies (e.g.G-CSF, GM-CSF)
- Currently on or scheduled for primary prophylaxis with antibiotics in the first chemotherapy cycle
- History of bone marrow transplantation or stem cell transplant
- Administration of another investigational medicinal product / medical device within 30 days prior to screening. Participation in non-interventional, national or international cancer registries is allowed.
- Already confirmed HIV, hepatitis B or C virus (HBV or HCV) infection
- History of somatic disease/condition that may interfere with the objectives of the study
- Any other medical disease or clinical laboratory parameter outside the normal range and of clinical significance according to the investigator
- Serious uncontrolled comorbidities
- Pregnant or breast-feeding subject
- Woman considered to be of childbearing potential who do not use highly effective birth control methods during the study.
Sites / Locations
- Site 20
- Site 16
- Site 21
- Site 26
- Site 05
- Site 09
- Site 02
- Site 13
- Site 01
- Site 25
- Site 11
- Site 10
- Site 22
- Site 07
- Site 29
- Site 03
- Site 23
- Site 04
- Site 19
- Site 17
- Site 24
- Site 28
- Site 12
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Myelo001
Placebo
Arm Description
Myelo001 100 mg QD
Matching Placebo QD
Outcomes
Primary Outcome Measures
Threshold area over the curve (AOC1) of ANC: Area below the threshold line (ANC 2.0x10^9/L classified as grade 1 neutropenia) and above the individual ANC trajectory
Threshold area over the curve (AOC3) of ANC: Area below the threshold line (ANC 1.0x10^9/L classified as grade 3 neutropenia) and above the individual ANC trajectory
Duration of ANC < 1.0x10^9/L classified as grade 3 neutropenia
Secondary Outcome Measures
Treatment success rate: a) Neutropenia grade ≤2, b) No need for G-CSF rescue therapy, c) No early withdrawal (drop-out).
Threshold AOC of ANC (AOC4): Area below the threshold line (ANC 0.5x10^9/L classified as grade 4 neutropenia) and above the individual ANC trajectory
Change of Threshold Area over the Curve of lymphocytes
Change of Threshold Area over the Curve of leukocytes
Change of Threshold Area over the Curve of thrombocytes
Proportion of patients with neutropenia grade 1 and higher; 3 and higher, 4, and ANC ≤0.1x 10^9/L
Duration of neutropenia grade 1 and higher; 3 and higher, 4, and ANC ≤0.1x 10^9/L
ANC at nadir
Time to ANC nadir (from start of chemotherapy)
Time to ANC recovery from grade 3 neutropenia, i. e. time from onset to time of reaching neutropenia grade ≤2 (ANC ≥ 1.5x10^9/L)
Time to ANC recovery from grade 4 neutropenia, i. e. time from onset to time of reaching neutropenia grade ≤2 (ANC ≥ 1.5x10^9/L)
Time to ANC recovery from profound neutropenia (ANC ≥ 0.1x10^9/L), i. e. time from onset to time of reaching neutropenia grade ≤2 (ANC ≥1.5x10^9/L)
Proportion of patients with rescue therapy
Proportion of patients developing febrile neutropenia (body temperature ≥38.3°C by single tympanic or oral measurement) and ANC ≤0.5x 10^9/L (Grade 4)
Proportion of patients with CTX dose reduction and/or delay of CTX cycle 2
Full Information
NCT ID
NCT02692742
First Posted
February 23, 2016
Last Updated
November 22, 2017
Sponsor
Myelo Therapeutics GmbH
1. Study Identification
Unique Protocol Identification Number
NCT02692742
Brief Title
Efficacy and Safety Phase IIa Study of Myelo001 in Chemotherapy-Induced Neutropenia
Acronym
MyeloConcept
Official Title
A Randomised, Double-Blind, Placebo-Controlled, Parallel-Design, Multi-Center Study to Investigate the Efficacy To Reduce Chemotherapy-Induced Neutropenia (CIN), Effects on the Haematopoietic System, Safety and Pharmacokinetics of Myelo001 in Patients Receiving Adjuvant or Neoadjuvant Chemotherapy for the Treatment Of Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
March 2016 (Actual)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
November 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Myelo Therapeutics GmbH
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Neutropenia is the most serious hematologic toxicity of cancer chemotherapy, often limiting the doses and density of chemotherapy that can be tolerated. The degree and duration of neutropenia determine the risk of infection. Myelo001, a small orally bioavailable molecule, has been shown in chemotherapy- or radiotherapy-induced myelosuppression to stimulate differentiation of peripheral white blood cells (WBC) and bone marrow cells of the leucocytic, lymphocytic, and erythrocytic lineage. The purpose of the MyeloConcept study is to determine the safety and effectiveness of Myelo001 in preventing or reducing chemotherapy-induced neutropenia and myelosuppression in patients receiving chemotherapy due to breast cancer.
Detailed Description
Phase IIa study, 1:1 randomized, double-blind, placebo-controlled, parallel-design, multi-center study. Each breast cancer patient will be randomly assigned into one of two treatment arms receiving either Myelo001 or placebo as a tablet. Investigational medicinal product is taken as supportive care for 23 consecutive days during chemotherapy treatment. Hematologic and safety parameters as well as actual begin and doses of following chemotherapy cycles will be assessed. A single primary variable will be analyzed with test statistics based on frequent absolute neutrophil measurements. Additionally, in a subgroup of patients biomarkers and pharmacokinetics of Myelo001 will be investigated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chemotherapy-Induced Neutropenia, Myelosuppression, Breast Cancer
Keywords
Chemotherapy, Chemotherapy-induced Neutropenia, Supportive Care, Myelosuppression, CIN
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
137 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Myelo001
Arm Type
Experimental
Arm Description
Myelo001 100 mg QD
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo QD
Intervention Type
Drug
Intervention Name(s)
Myelo001
Intervention Description
Intake of study drug once daily per os for a maximum of 28 days in addition to Epirubicin and Cyclophosphamide treatment
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intake of study drug once daily per os for a maximum of 28 days in addition to Epirubicin and Cyclophosphamide treatment
Primary Outcome Measure Information:
Title
Threshold area over the curve (AOC1) of ANC: Area below the threshold line (ANC 2.0x10^9/L classified as grade 1 neutropenia) and above the individual ANC trajectory
Time Frame
visit 3 to visit 10 (22 days)
Title
Threshold area over the curve (AOC3) of ANC: Area below the threshold line (ANC 1.0x10^9/L classified as grade 3 neutropenia) and above the individual ANC trajectory
Time Frame
visit 3 to visit 10 (22 days)
Title
Duration of ANC < 1.0x10^9/L classified as grade 3 neutropenia
Time Frame
visit 3 to visit 10 (22 days)
Secondary Outcome Measure Information:
Title
Treatment success rate: a) Neutropenia grade ≤2, b) No need for G-CSF rescue therapy, c) No early withdrawal (drop-out).
Time Frame
visit 3 to visit 10 (22 days)
Title
Threshold AOC of ANC (AOC4): Area below the threshold line (ANC 0.5x10^9/L classified as grade 4 neutropenia) and above the individual ANC trajectory
Time Frame
visit 3 to visit 10 (22 days)
Title
Change of Threshold Area over the Curve of lymphocytes
Time Frame
visit 3 to visit 10 (22 days)
Title
Change of Threshold Area over the Curve of leukocytes
Time Frame
visit 3 to visit 10 (22 days)
Title
Change of Threshold Area over the Curve of thrombocytes
Time Frame
visit 3 to visit 10 (22 days)
Title
Proportion of patients with neutropenia grade 1 and higher; 3 and higher, 4, and ANC ≤0.1x 10^9/L
Time Frame
visit 3 to visit 10 (22 days)
Title
Duration of neutropenia grade 1 and higher; 3 and higher, 4, and ANC ≤0.1x 10^9/L
Time Frame
visit 3 to visit 10 (22 days)
Title
ANC at nadir
Time Frame
visit 3 to visit 10 (22 days)
Title
Time to ANC nadir (from start of chemotherapy)
Time Frame
visit 3 to visit 10 (22 days)
Title
Time to ANC recovery from grade 3 neutropenia, i. e. time from onset to time of reaching neutropenia grade ≤2 (ANC ≥ 1.5x10^9/L)
Time Frame
visit 3 to visit 10 (22 days)
Title
Time to ANC recovery from grade 4 neutropenia, i. e. time from onset to time of reaching neutropenia grade ≤2 (ANC ≥ 1.5x10^9/L)
Time Frame
visit 3 to visit 10 (22 days)
Title
Time to ANC recovery from profound neutropenia (ANC ≥ 0.1x10^9/L), i. e. time from onset to time of reaching neutropenia grade ≤2 (ANC ≥1.5x10^9/L)
Time Frame
visit 3 to visit 10 (22 days)
Title
Proportion of patients with rescue therapy
Time Frame
visit 3 to visit 10 (22 days)
Title
Proportion of patients developing febrile neutropenia (body temperature ≥38.3°C by single tympanic or oral measurement) and ANC ≤0.5x 10^9/L (Grade 4)
Time Frame
visit 3 to visit 10 (22 days)
Title
Proportion of patients with CTX dose reduction and/or delay of CTX cycle 2
Time Frame
visit 10 to visit 11
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female patient of any racial origin having fulfilled her 18th birthday on Visit 1 (Screening)
Histologically confirmed invasive breast cancer scheduled for neoadjuvant or adjuvant chemotherapy (patient with primary wound healing ([R0])
Already selected for neoadjuvant or adjuvant standard of care EC regimen (Epirubicin 90 mg/m2 BSA (body surface area) + Cyclophosphamide 600 mg/m2 BSA q21d (every 21 days)) (with or without treatment with taxanes afterwards)
Risk of chemotherapy-induced Febrile Neutropenia ≤20% according to ASCO Guidelines (2015)
More than 5 days remaining before the planned initiation of the 1st chemotherapy cycle
Performance status Grade 0-1 (ECOG)
Echocardiography: No contraindication for the scheduled chemotherapy
Haematologic, laboratory and chemistry thresholds at baseline:
Absolute neutrophil count (ANC) ≥2,000 cells/ mm3 (≥2.0 x 10/L)
Platelet count ≥100,000/mm3 (≥100 x 10exp9/L)
Haemoglobin ≥10 g/dL
Total bilirubin <1.5 x, AST, ALT <2.5 x upper limit of normal (ULN)
Serum creatinine <2.0 mg/dL
Able to read, understand and willing to sign the informed consent form
Able to undergo the investigations and to follow the Visit schedule
Exclusion Criteria:
Suspected allergy to Myelo001 or its excipients
Prior chemotherapy
Prior or concomitant treatment with radiotherapy
Currently on or scheduled for other immunomodulatory or immunosuppressive therapies (e.g. TNF inhibitors) during the first chemotherapy cycle
Currently on or scheduled for other immunostimulatory or hematopoietic active therapies (e.g.G-CSF, GM-CSF)
Currently on or scheduled for primary prophylaxis with antibiotics in the first chemotherapy cycle
History of bone marrow transplantation or stem cell transplant
Administration of another investigational medicinal product / medical device within 30 days prior to screening. Participation in non-interventional, national or international cancer registries is allowed.
Already confirmed HIV, hepatitis B or C virus (HBV or HCV) infection
History of somatic disease/condition that may interfere with the objectives of the study
Any other medical disease or clinical laboratory parameter outside the normal range and of clinical significance according to the investigator
Serious uncontrolled comorbidities
Pregnant or breast-feeding subject
Woman considered to be of childbearing potential who do not use highly effective birth control methods during the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dirk Pleimes, MD
Organizational Affiliation
Myelo Therapeutics GmbH
Official's Role
Study Director
Facility Information:
Facility Name
Site 20
City
Aachen
Country
Germany
Facility Name
Site 16
City
Aurich
Country
Germany
Facility Name
Site 21
City
Dresden
Country
Germany
Facility Name
Site 26
City
Dresden
Country
Germany
Facility Name
Site 05
City
Erlangen
Country
Germany
Facility Name
Site 09
City
Esslingen
Country
Germany
Facility Name
Site 02
City
Frankfurt a.M.
Country
Germany
Facility Name
Site 13
City
Frankfurt a.M.
Country
Germany
Facility Name
Site 01
City
Friedrichshafen
Country
Germany
Facility Name
Site 25
City
Goslar
Country
Germany
Facility Name
Site 11
City
Hamburg
Country
Germany
Facility Name
Site 10
City
Hannover
Country
Germany
Facility Name
Site 22
City
Hannover
Country
Germany
Facility Name
Site 07
City
Konstanz
Country
Germany
Facility Name
Site 29
City
Lübeck
Country
Germany
Facility Name
Site 03
City
Mainz
Country
Germany
Facility Name
Site 23
City
Mainz
Country
Germany
Facility Name
Site 04
City
Offenbach
Country
Germany
Facility Name
Site 19
City
Oldenburg
Country
Germany
Facility Name
Site 17
City
Ravensburg
Country
Germany
Facility Name
Site 24
City
Rosenheim
Country
Germany
Facility Name
Site 28
City
Tübingen
Country
Germany
Facility Name
Site 12
City
Westerstede
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.myelotherapeutics.com
Description
Company homepage
Learn more about this trial
Efficacy and Safety Phase IIa Study of Myelo001 in Chemotherapy-Induced Neutropenia
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