Myelofibrosis MedDRA version: 21.0 Level: LLT Classification code 10074692 Term: Post essential thrombocythaemia myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10074691 Term: Post polycythaemia vera myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10077161 Term: P
Conditions
Sponsors
Imago BioSciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to sign the approved informed consent. 2. Age: 18+ years old at Screening. 3. Diagnosis of either PMF per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Section 16.2), PPV-MF per the IWG-MRT (Section 16.3), or PET-MF per the IWG-MRT (Section 16.4) and meet the following additional subtype specific criteria: a. Classified as high risk (3 prognostic factors) intermediate risk-2 (2 prognostic factors) or intermediate risk-1 (1 prognostic factor). The prognostic factors, defined by the International Working Group (Cervantes, et al., 2009): i. Age > 65 years; ii. Presence of constitutional symptoms (weight loss, fever, night sweats); iii. Marked anaemia (Hgb 25 x109/L (25,000/µL)]; v. Circulating blasts = 1%. *A haemoglobin value 36 weeks. 10. Have discontinued all previous therapies for MPNs including ruxolitinib, any chemotherapeutic agents, immunosuppressive therapy (e.g., corticosteroids > 10 mg/day with the noted exception: use of corticosteroids for management of gout is allowed; maintenance supplemental corticosteroid therapy such as prednisone = 10 mg/day or corticosteroid equivalent is allowed), immune modulators (e.g., thalidomide), radiotherapy for at least 2 weeks prior, and interferon for 4 weeks prior to study Day 0. Low dose acetylsalicyclic acid is permitted. Palliative radiation treatment to non-index or bone lesions performed 10 half-lives of the drug at th
Exclusion criteria
Exclusion criteria: 1. Has undergone major surgery =4 weeks prior to starting study drug or has not recovered from side effects of such surgery. 2. Has undergone any surgical procedure within 2 weeks, excluding minor procedures (e.g., skin biopsy or central venous catheter placement/removal) prior to starting study drug. 3. History of splenectomy. 4. History of or scheduled haematopoietic stem-cell transplant within 24 weeks of screening. 5. Unresolved treatment related toxicities from prior therapies (unless resolved to = Grade 1). 6. Current use of a prohibited medication (e.g., romiplostim) or expected to require any of these medications during treatment with the investigational drug. 7. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to IMG-7289 or LSD1 inhibitors (i.e., monoamine oxidase inhibitors; MAOIs) that contraindicates their participation. 8. Current use of monoamine oxidase A and B inhibitors (MAOIs). 9. Uncontrolled active infection. 10. A concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, such as non-melanoma skin cancers, are eligible). 11. Evidence at the time of Screening of risk of bleeding, including any of the following: a. Activated partial thromboplastin time (aPTT) = 1.3 x the local upper limit of normal b. International normalized ratio (INR) = 1.3 x the local upper limit of normal c. History of severe thrombocytopenia or platelet dysfunction unrelated to a myeloproliferative disorder or its treatment d. Known bleeding disorder (e.g., dysfibrinogenaemia, factor IX deficiency, haemophilia, Von Willebrand's disease, Disseminated Intravascular Coagulation [DIC], fibrinogen deficiency, or other clotting factor deficiency) 12. Evidence at the time of Screening of significant renal or hepatic insufficiency (unless due to haemolysis, or leukaemic infiltration) as defined by any of the following local lab parameters: a. Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) 1.5 x the local upper limit of normal b. Aspartate transaminase (AST) or alanine aminotransferase (ALT) =2 x the local upper limit of normal 13. Known human immunodeficiency virus (HIV) infection or known active Hepatitis B or Hepatitis C virus infection (testing will not be conducted as part of Screening procedures). For Italy ONLY, Exclusion 13 reads: Active infection with hepatitis B virus (positive hepatitis B surface antigen; note: positive hepatitis B surface antibody and positive hepatitis B core antibody are not exclusionary provided disease is not active, which should be clearly documented in the patient's medical history) or C virus (patients with positive hepatitis C antibody result would require confirmation of active disease with a positive hepatitis C polymerase chain reaction (PCR) test), seropositivity for human immunodeficiency virus HIV). 14. History of any illness/impairment of gastrointestinal (GI) function that might interfere with drug absorption (e.g., chronic diarrhea), confound the study results or pose an additional risk to the patient by participation in the study; patients with gastric bypass surgery. 15. Use of an investigational agent within less than 14 days, or the equivalent of at least 7 half-lives of that agent, whichever is the longer, prior to study Day 0. 16. Pregnant or lactating females; females intending to become pregnant within 6 months; females intending t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate in MF patients the effect of IMG-7289 on: • Safety and tolerability • Pharmacokinetics (Phase 1/2a only) - NA for EU • Reduction in spleen volume To evaluate the safety and tolerability of IMG-7289 when administered orally on a daily basis to patients with myelofibrosis. This will be evaluated by clinical assessments of safety parameters i.e. safety laboratory testing, adverse event reporting, physical examination and vital sign assessments. The second primary objective is to assess the change in spleen volume due to treatment with IMG-7289. An additional objective for the phase 1/2a portion of this study (which is already complete) was to assess the pharmacokinetics of IMG-7289 (The EU will participate in the phase 2b expansion protocol and this assessment will not be made in patients enrolled here; no further detail provided on PK in this application) ;Secondary Objective: Not applicable;Primary end point(s): The safety and tolerability of IMG-7289 will be assessed by the analysis of adverse events (AEs), as well as changes in physical examinations, vital signs and laboratory values as detailed below. o Monitoring of Adverse Events (AEs) including determination of dose limiting toxicities (DLTs), serious adverse events (SAEs), and AEs. AEs will be assessed post-first dose until 28 days post-last dose in terms of onset, duration, seriousness, severity, and causality, using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03. Deaths and other serious adverse events (SAEs) will also be evaluated and will be collected on a separate electronic case report form (eCRF). o Changes in physical examinations, vital signs and laboratory values will also be evaluated and assessed from Screening/Baseline until EoS/ET. Information on the timing of these assessments is presented in the schedule of assessment. The following laboratory tests will be conducted: ? Complete blood counts (CBC) and differenti | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): NA;Timepoint(s) of evaluation of this end point: NA | — |
Countries
Australia, Germany, Italy, United Kingdom, United States
Contacts
Public ContactAmber Jones
Imago BioSciences B.V.
Outcome results
None listed