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

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ClinicalTrials.gov Identifier: NCT04262141
Recruitment Status : Recruiting
First Posted : February 10, 2020
Last Update Posted : March 24, 2021
Sponsor:
Collaborator:
Imago BioSciences,Inc.
Information provided by (Responsible Party):
Terrence J Bradley, MD, University of Miami

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Essential Thrombocythemia Polycythemia Vera Drug: IMG-7289 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 2, 2020
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2023


Arm Intervention/treatment
Experimental: IMG-7289 in ET and PV Patients

Oral 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.
Drug: IMG-7289
Daily oral dose of 0.6 mg/kg/day IMG-7829 capsules. Dose escalation an de-escalation rules applied as necessary.
Other Names:
  • IMG7289
  • IMG 7289




Primary Outcome Measures :
  1. Hematologic Response Rates [ Time Frame: 24 Weeks ]
    As evaluated by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) response criteria.


Secondary Outcome Measures :
  1. Incidence of Treatment-Related Toxicity [ Time Frame: Up to 3 Years ]
    As evaluated by the treating physician using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

  2. Change in Total Symptom Score (TSS) as Measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) [ Time Frame: Baseline, Up to 3 Years ]
    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).

  3. Change in Mutational Allele Burden [ Time Frame: Baseline, Up to 3 Years ]
    Evaluated via Next Generation Sequencing (NGS) molecular profiling from serum blood sample.

  4. Change in Spleen Size in Centimeters [ Time Frame: Baseline, Up to 3 Years ]
    Measured via physical examination and radiologic imaging measurement.

  5. Change in Fibrosis Score [ Time Frame: Baseline, Up to 3 Years ]
    Assessed using a slightly modified version of European Consensus Criteria for Grading Myelofibrosis from bone marrow/aspirate sample, as presented in Thiele et al, 2005. Myelofibrosis (MF) scores are graded on a four-point scale, from MF-0 to MF-3, grading the reticulin and collagen content of bone marrow, with MF-0 being the lowest and MF-3 the highest.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 >400 x 10^9/L pre-dose Day 1for patients with essential thrombocytopenia.
  5. Platelet count >150 x 10^9/L pre-dose Day 1 for patients with polycythemia vera.
  6. Peripheral blast count < 10% pre-dose Day 1.
  7. Absolute neutrophil count (ANC) ≥ 0.5 x 10^9/L pre-dose Day 1.
  8. 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).
  9. Life expectancy > 36 weeks.
  10. Able to swallow capsules.
  11. Amenable to blood draws, spleen size determination, bone marrow evaluations, and peripheral blood sampling during the study.
  12. Must have discontinued prior therapy for condition under study for 2 weeks (4 weeks for interferon) prior to study drug initiation.
  13. Agrees to use an approved method of contraception from Screening until 28 days after last administration of the study drug.
  14. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04262141


Contacts
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Contact: Leanne Rodriguez 305-243-2383 lmr248@med.miami.edu

Locations
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United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Leanne Rodriguez    305-243-2383    lmr248@med.miami.edu   
Principal Investigator: Terrence J Bradley, MD         
Sponsors and Collaborators
Terrence J Bradley, MD
Imago BioSciences,Inc.
Investigators
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Principal Investigator: Terrence J Bradley, MD University of Miami
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Responsible Party: Terrence J Bradley, MD, Assistant Professor, University of Miami
ClinicalTrials.gov Identifier: NCT04262141    
Other Study ID Numbers: 20190932
First Posted: February 10, 2020    Key Record Dates
Last Update Posted: March 24, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Polycythemia Vera
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Bone Marrow Diseases
Myeloproliferative Disorders
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders