A Study of LY2784544 in patients with blood cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eli Lilly & Co.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 Oct 2012 → ongoing

Decision date (initial)

2024-12-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-514254-69-00

EudraCT number

2011-001012-56

WHO UTN

U1111-1308-7154

ClinicalTrials.gov

NCT01594723

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Dose response, Efficacy, Safety, Pharmacogenetic, Pharmacokinetic, Pharmacodynamic

The primary objective of this study is to assess the activity of LY2784544 therapy administered once daily, as measured by objective response rate, in patients with the myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF).

Conditions and MedDRA coding

Myeloproliferative neoplasms (MPNs), myelofibrosis, essential thrombocythemia, and polycythemia vera

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Have a diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF) as defined by the World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms
2. have failed or is intolerant of standard therapies or refuses to take standard medications.
3. have failed or is intolerant of standard therapies or refuses to take standard medications.
4. have intermediate 1, intermediate 2, or high-risk MF according to the Dynamic International Prognostic Scoring System (DIPPS Plus) for Primary Myelofibrosis (Gangat et al. 2011); or ii. have symptomatic MF with spleen greater than 10 cm below left costal margin; or iii. have post-polycythemic MF; or iv. have post-ET MF
5. Have a quantifiable JAK2 V617F mutation. This inclusion criterion will not apply to the subset of patients in Cohorts 10 and 11 that must be negative for the JAK2 V617F mutation. This subset of patients must be negative for the mutation with unquantifiable levels of JAK2 V617F.
6. Are ³18 years of age.
7. Have given written informed consent prior to any study-specific procedures.
8. Have adequate organ function.
9. Have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) scale
10. Have discontinued all previous approved therapies for MPNs, including any chemotherapy, immunomodulating therapy (for example, thalidomide, interferon-alpha), immunosuppressive therapy (for example, corticosteroids >10 mg/day prednisone or equivalent), radiotherapy, and erythropoietin, thrombopoietin, or granulocyte colony stimulating factor for at least 14 days and recovered from the acute effects of therapy. Hydroxyurea used to control blood cell counts is permitted at study entry if the subject has been maintained on a stable dose for at least 4 weeks. Low-dose acetylsalicylic acid (aspirin 80 or 100mg) is permitted as well.
11. Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
12. Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of study drug.
13. Females with child-bearing potential must have had a negative urine pregnancy test £7 days before the first dose of study drug and must also not be breastfeeding.
14. Are able to swallow capsules.
15. For patients who have undergone recent major surgery, at least 28 days must have elapsed between surgery and study participation and the subject must have achieved, in the opinion of the treating physician, at least a good recovery from the surgical procedure
16. Enrollment into Cohort 12 is limited to MF, PV or ET patients, regardless of mutational status, who, in addition to all other criteria, have demonstrated intolerance to ruxolitinib, failure of primary response to ruxolitinib, or have demonstrated disease progression while on ruxolitinib

Exclusion criteria 9

1. Are currently enrolled in, or discontinued within the last 14 days from a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
2. Have a corrected QT (QTc) interval >470 msec using Bazett's formula.
3. Have serious preexisting medical conditions that, in the opinion of the investigator would preclude participation in the study (for example a gastrointestinal disorder causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndrome).
4. Are currently being treated with agents that are metabolized by CYP3A4 with a narrow therapeutic margin (for example, alfentanil, cyclosporine, diergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus) or CYP2B6 (for example, cyclophosphamide, ifosfamide, tamoxifen, efavirenz, propofol, methadone, and bupropion).
5. Are currently being treated with warfarin or 1 of its derivatives which is known to alter levels of protein C or protein S. An exception to this criterion will be allowed for patients with a prior history of Budd-Chiari Syndrome who are being treated with warfarin or 1 of its derivatives.
6. Have received a hematopoietic stem cell transplant.
7. Have a second primary malignancy that in the judgment of the Investigator and Sponsor may affect the interpretation of results.
8. Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required).
9. Have a history of congestive heart failure with New York Heart Association Class >2 (NYHA Class 1 and 2 are eligible), unstable angina, recent myocardial infarction (within 6 months prior to administration of study drug), or documented history of ventricular arrhythmia.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary objective of this study is to assess the activity of LY2784544 therapy administered once daily, as measured by objective response rate, in patients with the myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocytopenia (ET) or myelofibrosos (MF) including those who have demonstrated an intolerance to, failure of primary response to, or have demonstarted disease progression while on ruxolitinib.

Secondary endpoints 1

1. To characterise the toxicity profile To assess response criteria To assess efficacy To characterise PD-PHK

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eli Lilly & Co.

Sponsor organisation

Eli Lilly & Co.

Address

1 Lilly Corporate Center

City

Indianapolis

Postcode

46285-0001

Country

United States

Scientific contact point

Organisation

Eli Lilly & Co.

Contact name

Lilly Clinical Trials information desk

Public contact point

Organisation

Eli Lilly & Co.

Contact name

Lilly Clinical Trials information desk

Third parties 7

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications