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

• Sponsor: Myelo Therapeutics GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02692742
• Collaborator: (none)
• Enrollment: 137
• Locations: 23
• Arms: 2
• Actual Duration (Months): 20
• Patients Per Site: 6
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Chemotherapy-Induced Neutropenia; Myelosuppression; Breast Cancer	Drug: Myelo001; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 137 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• 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
• Actual Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Nov 1, 2017
• Actual Study Completion Date: Nov 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Myelo001 Myelo001 100 mg QD	Drug: Myelo001; Intake of study drug once daily per os for a maximum of 28 days in addition to Epirubicin and Cyclophosphamide treatment
Placebo Comparator: Placebo Matching Placebo QD	Drug: Placebo; Intake of study drug once daily per os for a maximum of 28 days in addition to Epirubicin and Cyclophosphamide treatment

Outcome Measures

Primary Outcome Measures

1. 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)]

2. 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)]

3. Duration of ANC < 1.0x10^9/L classified as grade 3 neutropenia [visit 3 to visit 10 (22 days)]

Secondary Outcome Measures

1. 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)]

2. 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)]

3. Change of Threshold Area over the Curve of lymphocytes [visit 3 to visit 10 (22 days)]

4. Change of Threshold Area over the Curve of leukocytes [visit 3 to visit 10 (22 days)]

5. Change of Threshold Area over the Curve of thrombocytes [visit 3 to visit 10 (22 days)]

6. 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)]

7. 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)]

8. ANC at nadir [visit 3 to visit 10 (22 days)]

9. Time to ANC nadir (from start of chemotherapy) [visit 3 to visit 10 (22 days)]

10. 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)]

11. 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)]

12. 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)]

13. Proportion of patients with rescue therapy [visit 3 to visit 10 (22 days)]

14. 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)]

15. Proportion of patients with CTX dose reduction and/or delay of CTX cycle 2 [visit 10 to visit 11]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

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

2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 20	Aachen		Germany
2	Site 16	Aurich		Germany
3	Site 21	Dresden		Germany
4	Site 26	Dresden		Germany
5	Site 05	Erlangen		Germany
6	Site 09	Esslingen		Germany
7	Site 02	Frankfurt a.M.		Germany
8	Site 13	Frankfurt a.M.		Germany
9	Site 01	Friedrichshafen		Germany
10	Site 25	Goslar		Germany
11	Site 11	Hamburg		Germany
12	Site 10	Hannover		Germany
13	Site 22	Hannover		Germany
14	Site 07	Konstanz		Germany
15	Site 29	Lübeck		Germany
16	Site 03	Mainz		Germany
17	Site 23	Mainz		Germany
18	Site 04	Offenbach		Germany
19	Site 19	Oldenburg		Germany
20	Site 17	Ravensburg		Germany
21	Site 24	Rosenheim		Germany
22	Site 28	Tübingen		Germany
23	Site 12	Westerstede		Germany

Sponsors and Collaborators

• Myelo Therapeutics GmbH

Investigators

• Study Director: Dirk Pleimes, MD, Myelo Therapeutics GmbH

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Company homepage

Publications

None provided.

• Responsible Party: Myelo Therapeutics GmbH
• ClinicalTrials.gov Identifier: NCT02692742
• Other Study ID Numbers: CT-MT001-2-2015-1; 2015-003610-25
• First Posted: Feb 26, 2016
• Last Update Posted: Nov 24, 2017
• Last Verified: Nov 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Myelo Therapeutics GmbH: Chemotherapy; Chemotherapy-induced Neutropenia; Supportive Care; Myelosuppression; CIN
• Additional relevant MeSH terms: Breast Neoplasms; Neutropenia

Study Results

No Results Posted as of Nov 24, 2017