Clinical Trials /

IMG-7289 in Patients With Essential Thrombocythemia (ET) or Polycythemia Vera (PV)

NCT04262141

Description:

The purpose of this study is to assess the hematologic effects of IMG-7289 therapy in ET and PV patients who require platelet, White Blood Cell (WBC) or Red Blood Cell (RBC) control, and have failed at least one standard therapy.

Related Conditions:
  • Essential Thrombocythemia
  • Polycythemia Vera
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: IMG-7289 in Patients With Essential Thrombocythemia (ET) or Polycythemia Vera (PV)
  • Official Title: Investigator-Initiated Trial of the LSD1 Inhibitor IMG-7289 for the Treatment of Patients With Essential Thrombocythemia (ET) or Polycythemia Vera (PV) That Have Failed at Least One Standard Therapy

Clinical Trial IDs

  • ORG STUDY ID: 20190932
  • NCT ID: NCT04262141

Conditions

  • Essential Thrombocythemia
  • Polycythemia Vera

Interventions

DrugSynonymsArms
IMG-7289IMG7289, IMG 7289IMG-7289 in ET and PV Patients

Purpose

The purpose of this study is to assess the hematologic effects of IMG-7289 therapy in ET and PV patients who require platelet, White Blood Cell (WBC) or Red Blood Cell (RBC) control, and have failed at least one standard therapy.

Trial Arms

NameTypeDescriptionInterventions
IMG-7289 in ET and PV PatientsExperimentalOral daily dose of 0.6 mg/kg/day IMG-7289 will be administered: The initial pilot period will enroll 8 participants to receive oral daily dose of IMG-7829 for 24 weeks, iteratively as long as there is clinical benefit in the absence of excess toxicity. The second stage group will enroll an additional 16 participants to receive IMG-7829 for over 2 years, iteratively as long as there is clinical benefit in the absence of toxicity.
  • IMG-7289

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 18 years.

          2. Diagnosis of Essential Thrombocythemia or Polycythemia Vera per World Health
             Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Arber et al.,
             2016).

          3. Patients that have failed at least one standard therapy (failure is the equivalent of
             inadequate response or intolerance).

          4. Platelet count > 450 x 10^9/L pre-dose Day 1.

          5. Peripheral blast count < 10% pre-dose Day 1.

          6. Absolute neutrophil count (ANC) ≥ 0.5 x 10^9/L pre-dose Day 1.

          7. Fibrosis score ≤ grade 2, as per a slightly modified version (Arber et al., 2016) of
             the European Consensus Criteria for Grading Myelofibrosis, (Thiele et al., 2005).

          8. Life expectancy > 36 weeks.

          9. Able to swallow capsules.

         10. Amenable to blood draws, spleen size determination, bone marrow evaluations, and
             peripheral blood sampling during the study.

         11. Must have discontinued prior therapy for condition under study for 2 weeks (4 weeks
             for interferon) prior to study drug initiation.

         12. Agrees to use an approved method of contraception from Screening until 28 days after
             last administration of the study drug.

         13. If male, agrees not to donate sperm or father a child for at least one month after the
             last dose of the study medication.

        Exclusion Criteria:

          1. Eastern Cooperative Oncology Group (ECOG) questionnaire score of 3 or greater.

          2. Currently pregnant, planning on being pregnant in the following 6 months or currently
             breastfeeding.

          3. Currently residing outside the United States.

          4. History of splenectomy.

          5. Unresolved treatment related toxicities from prior therapies (unless resolved to ≤
             Grade 1).

          6. Uncontrolled active infection.

          7. Known positive for HIV if not well-controlled (i.e., undetectable viral load), or
             infectious hepatitis, type A, B or C.

          8. Current use of monoamine oxidase A and B inhibitors (MAOIs).

          9. Evidence at the time of screening of increased risk of bleeding, including any of the
             following:

               -  Activated partial thromboplastin time (aPTT) > 1.3 x the upper limit of normal

               -  International normalized ratio (INR) >1.3 x the local upper limit of normal

               -  History of severe thrombocytopenia or platelet dysfunction unrelated to a
                  myeloproliferative disorder or its treatment

               -  Known bleeding disorder (e.g., dysfibrinogenaemia, factor IX deficiency,
                  haemophilia, Von Willebrand's disorder, Disseminated Intravascular Coagulation
                  [DIC], fibrinogen deficiency, or other clotting factor deficiency)

         10. 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:

               1. Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) <
                  40 mL/min or serum creatinine > 1.5 x the local upper limit of normal

               2. Aspartate transaminase (AST) or alanine aminotransferase (ALT) ≥ 2 x the local
                  upper limit of normal

         11. Current use of a prohibited medication (e.g., romiplostim) or expected to require any
             of these medications during treatment with the investigational drug.

         12. 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.

         13. Patients with impaired decision-making capacity.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Hematologic Response Rates
Time Frame:24 Weeks
Safety Issue:
Description:As evaluated by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) response criteria.

Secondary Outcome Measures

Measure:Incidence of Treatment-Related Toxicity
Time Frame:Up to 3 Years
Safety Issue:
Description:As evaluated by the treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Measure:Change in Total Symptom Score (TSS) as Measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
Time Frame:Baseline, Up to 3 Years
Safety Issue:
Description:As measured using the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) that includes 14 disease related symptoms each scored from 0 (absent) to 10 (worst imaginable).
Measure:Change in Mutational Allele Burden
Time Frame:Baseline, Up to 3 Years
Safety Issue:
Description:Evaluated via Next Generation Sequencing (NGS) molecular profiling from serum blood sample.
Measure:Change in Spleen Size in Centimeters
Time Frame:Baseline, Up to 3 Years
Safety Issue:
Description:Measured via physical examination and radiologic imaging measurement.
Measure:Change in Fibrosis Score
Time Frame:Baseline, Up to 3 Years
Safety Issue:
Description:Assessed using the European Consensus Criteria for Grading Myelofibrosis from bone marrow/aspirate sample.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Terrence J Bradley, MD

Last Updated

February 6, 2020