Efficacy and Safety Phase IIa Study of Myelo001 in Chemotherapy-Induced Neutropenia

Breast Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02692742
• Other study ID #: CT-MT001-2-2015-1
• Secondary ID: 2015-003610-25
• Status: Completed
• Phase: Phase 2
• First received: February 23, 2016
• Last updated: November 22, 2017
• Start date: March 2016
• Est. completion date: November 2017

Study information

• Verified date: November 2017
• Source: Myelo Therapeutics GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 137
• Est. completion date: November 2017
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Female patient of any racial origin having fulfilled her 18th birthday on Visit 1 (Screening)

2. Histologically confirmed invasive breast cancer scheduled for neoadjuvant or adjuvant chemotherapy (patient with primary wound healing ([R0])

3. 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)

4. Risk of chemotherapy-induced Febrile Neutropenia =20% according to ASCO Guidelines (2015)

5. More than 5 days remaining before the planned initiation of the 1st chemotherapy cycle

6. Performance status Grade 0-1 (ECOG)

7. Echocardiography: No contraindication for the scheduled chemotherapy

8. 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

9. Able to read, understand and willing to sign the informed consent form

10. Able to undergo the investigations and to follow the Visit schedule

Exclusion Criteria:

1. Suspected allergy to Myelo001 or its excipients

2. Prior chemotherapy

3. Prior or concomitant treatment with radiotherapy

4. Currently on or scheduled for other immunomodulatory or immunosuppressive therapies (e.g. TNF inhibitors) during the first chemotherapy cycle

5. Currently on or scheduled for other immunostimulatory or hematopoietic active therapies (e.g.G-CSF, GM-CSF)

6. Currently on or scheduled for primary prophylaxis with antibiotics in the first chemotherapy cycle

7. History of bone marrow transplantation or stem cell transplant

8. 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.

9. Already confirmed HIV, hepatitis B or C virus (HBV or HCV) infection

10. History of somatic disease/condition that may interfere with the objectives of the study

11. Any other medical disease or clinical laboratory parameter outside the normal range and of clinical significance according to the investigator

12. Serious uncontrolled comorbidities

13. Pregnant or breast-feeding subject

14. Woman considered to be of childbearing potential who do not use highly effective birth control methods during the study.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Chemotherapy-Induced Neutropenia
• Myelosuppression
• Neutropenia

Intervention

Drug:
• Myelo001
Intake of study drug once daily per os for a maximum of 28 days in addition to Epirubicin and Cyclophosphamide treatment
• Placebo
Intake of study drug once daily per os for a maximum of 28 days in addition to Epirubicin and Cyclophosphamide treatment

Locations

Country	Name	City	State
Germany	Site 20	Aachen
Germany	Site 16	Aurich
Germany	Site 21	Dresden
Germany	Site 26	Dresden
Germany	Site 05	Erlangen
Germany	Site 09	Esslingen
Germany	Site 02	Frankfurt a.M.
Germany	Site 13	Frankfurt a.M.
Germany	Site 01	Friedrichshafen
Germany	Site 25	Goslar
Germany	Site 11	Hamburg
Germany	Site 10	Hannover
Germany	Site 22	Hannover
Germany	Site 07	Konstanz
Germany	Site 29	Lübeck
Germany	Site 03	Mainz
Germany	Site 23	Mainz
Germany	Site 04	Offenbach
Germany	Site 19	Oldenburg
Germany	Site 17	Ravensburg
Germany	Site 24	Rosenheim
Germany	Site 28	Tübingen
Germany	Site 12	Westerstede

Sponsors (1)

Lead Sponsor	Collaborator
Myelo Therapeutics GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		visit 3 to visit 10 (22 days)
Primary	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		visit 3 to visit 10 (22 days)
Primary	Duration of ANC < 1.0x10^9/L classified as grade 3 neutropenia		visit 3 to visit 10 (22 days)
Secondary	Treatment success rate: a) Neutropenia grade =2, b) No need for G-CSF rescue therapy, c) No early withdrawal (drop-out).		visit 3 to visit 10 (22 days)
Secondary	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		visit 3 to visit 10 (22 days)
Secondary	Change of Threshold Area over the Curve of lymphocytes		visit 3 to visit 10 (22 days)
Secondary	Change of Threshold Area over the Curve of leukocytes		visit 3 to visit 10 (22 days)
Secondary	Change of Threshold Area over the Curve of thrombocytes		visit 3 to visit 10 (22 days)
Secondary	Proportion of patients with neutropenia grade 1 and higher; 3 and higher, 4, and ANC =0.1x 10^9/L		visit 3 to visit 10 (22 days)
Secondary	Duration of neutropenia grade 1 and higher; 3 and higher, 4, and ANC =0.1x 10^9/L		visit 3 to visit 10 (22 days)
Secondary	ANC at nadir		visit 3 to visit 10 (22 days)
Secondary	Time to ANC nadir (from start of chemotherapy)		visit 3 to visit 10 (22 days)
Secondary	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)		visit 3 to visit 10 (22 days)
Secondary	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)		visit 3 to visit 10 (22 days)
Secondary	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)		visit 3 to visit 10 (22 days)
Secondary	Proportion of patients with rescue therapy		visit 3 to visit 10 (22 days)
Secondary	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)		visit 3 to visit 10 (22 days)
Secondary	Proportion of patients with CTX dose reduction and/or delay of CTX cycle 2		visit 10 to visit 11

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