Clinical Trials /

IO-202 as Monotherapy in Patients in AML and CMML

NCT04372433

Description:

To assess safety and tolerability at increasing dose levels of IO-202 in successive cohorts of participants with relapsed or refractory monocytic AML and CMML in order to estimate the maximum tolerated dose (MTD) or maximum administered dose (MAD) and select the recommended Phase 2 dose (RP2D) and dose schedule as monotherapy.

Related Conditions:
  • Acute Monoblastic and Monocytic Leukemia
  • Acute Myelomonocytic Leukemia
  • Chronic Myelomonocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: IO-202 as Monotherapy in Patients in AML and CMML
  • Official Title: A Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion Study of Intravenously Administered IO-202 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Chronic Myelomonocytic Leukemia (CMML)

Clinical Trial IDs

  • ORG STUDY ID: IO-202-CL-001
  • NCT ID: NCT04372433

Conditions

  • AML M5
  • AML M4
  • AML, Nos
  • Acute Myelogenous Leukemia in Relapse
  • Myelomonocytic Leukemia, Chronic

Interventions

DrugSynonymsArms
IO-202 Dose EscalationDose Escalation
IO-202 Dose ExpansionDose Expansion

Purpose

To assess safety and tolerability at increasing dose levels of IO-202 in successive cohorts of participants with relapsed or refractory monocytic AML and CMML in order to estimate the maximum tolerated dose (MTD) or maximum administered dose (MAD) and select the recommended Phase 2 dose (RP2D) and dose schedule as monotherapy.

Detailed Description

      This is a Phase 1, Multicenter, Open-Label, Dose-Escalation and Dose Expansion Study to
      Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity
      Study of IO-202 as Monotherapy in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients
      with Monocytic Differentiation and in Relapsed/Refractory Chronic Myelomonocytic Leukemia
      (CMML) Patients.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalDose cohorts treated with intravenous (IV) IO-202 monotherapy, in ascending doses Q2wks.
  • IO-202 Dose Escalation
Dose ExpansionExperimentalIV IO-202 monotherapy at the recommended Phase 2 dose and frequency
  • IO-202 Dose Expansion

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must be ≥18.

          2. For the Part 1 Dose-Escalation Phase, patients must be diagnosed with the following:

               1. Relapsed AML with myelomonocytic or monoblastic/monocytic differentiation
                  according to the World Health Organization (WHO) 2016 criteria and has failed
                  treatment with available therapies known to be active for AML.

               2. CMML according to World Health Organization (WHO) 2016 criteria and has failed
                  treatment with available therapies known to be active for CMML.

          3. Part 2 Expansion Phase:

             a) AML with myelomonocytic or monoblastic/monocytic differentiation according to the
             World Health Organization 2016 criteria and has failed treatment with available
             therapies known to be active for AML.

          4. Patients must be amenable to serial BM aspirates/biopsies and peripheral blood
             sampling during the study.

          5. Patients must be able to understand and willing to sign an informed consent. A legally
             authorized representative may consent on behalf of a patient who is otherwise unable
             to provide informed consent, if acceptable to and approved by the site and/or site's
             Institutional Review Board (IRB) or Ethics Committee.

          6. Patients must have an ECOG performance status of 0 to 2, inclusive.

          7. Patients must have adequate hepatic function

          8. Patients must have adequate renal function

          9. Patients must be recovered from any clinically relevant toxic effects of any prior
             surgery, radiotherapy, or other therapy intended for the treatment of cancer (patients
             with residual Grade 1 toxicity, or any grade of alopecia, are allowed; patients with
             peripheral neuropathy that is not more than Grade 2 and stable are allowed).

         10. Patients must be off calcineurin inhibitors (e.g., cyclosporine, tacrolimus) for at
             least 4 weeks prior to study drug treatment.

         11. Female patients with reproductive potential must have a negative serum pregnancy test
             within 7 days prior to the start of therapy.

        Exclusion Criteria:

          1. Patients who have previously received IO-202.

          2. Patients who have undergone HSCT within 60 days of the first dose of IO-202, or
             patients on immunosuppressive therapy post human stem cell transplantation (HSCT) at
             the time of screening, or with clinically significant graft-versus-host disease (GVHD)
             (the use of a stable dose of oral steroids post-HSCT of <10 mg prednisone/day or dose
             equivalent of other corticosteroid and/or topical steroids for ongoing skin GVHD is
             permitted with Medical Monitor approval).

          3. Patients who received systemic anti-cancer therapy or radiotherapy <7 days prior to
             their first day of study drug administration (Hydroxyurea or leukapheresis is allowed
             up to 24 hours prior to the first dose. However, hydroxyurea must be ceased 24 hours
             prior to the first dose of IO-202 treatment in Cycle 1).

          4. Patients who received an investigational agent <7 days prior to their first day of
             study drug administration. In addition, the first dose of IO-202 should not occur
             before a period ≥5 half-lives of the investigational agent has elapsed.

          5. Patients for whom potentially curative anti-cancer therapy is available.

          6. Patients who are pregnant or breast feeding.

          7. Patients with uncontrolled, active infection.

          8. Patients with known hypersensitivity to any of the components of the IO-202
             formulation.

          9. History of another malignancy in the previous 5 years, unless cured by surgery alone
             and continuously disease free. Exceptions include appropriately treated carcinoma in
             situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, localized
             prostate cancer that has been treated surgically with curative intent and presumed
             cured, resected breast cancer that has been treated with or is currently being treated
             with adjuvant hormonal and/or other endocrine therapy, resected prostate cancer that
             has been treated with androgen deprivation therapy and prostate-specific antigen level
             is stable or 0.

         10. Patients with New York Heart Association (NYHA) Class III or IV congestive heart
             failure (CHF) or left ventricular ejection fraction (LVEF) <40% by echocardiogram
             (ECHO) or multi-gated acquisition (MUGA) scan ≤28 days prior to Cycle 1, Day 1.

         11. Any of the following in the previous 6 months: myocardial infarction, congenital long
             QT syndrome, Torsades de pointes, clinically significant arrhythmias (including
             sustained ventricular tachyarrhythmia and ventricular fibrillation), and left anterior
             hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass
             graft, symptomatic CHF (NYHA class III or IV), cerebrovascular accident, transient
             ischemic attack, or pulmonary embolism. Patients with asymptomatic right bundle branch
             block are allowed.

         12. Ongoing cardiac dysrhythmias of NCI CTCAE, Version 5.0, Grade ≥2 or QT interval
             corrected by Fridericia's formula (QTcF) interval >470 msec at screening.

         13. Known or suspected hypersensitivity to recombinant human proteins.

         14. Active bacterial, viral, and/or fungal infection including hepatitis B (HB), hepatitis
             C, human immunodeficiency virus (HIV), acquired immunodeficiency syndrome
             (AIDS)-related illness, or active Covid-19 infection.

         15. Patients with any psychological, familial, sociological, or geographical condition
             potentially hampering compliance with the study protocol and follow-up schedule; those
             conditions should be discussed with the patient before trial entry.

         16. Patients with clinical signs and/or symptoms suggesting active, uncontrolled central
             nervous system (CNS) leukemia or known active, uncontrolled CNS leukemia (a lumbar
             puncture is not required in patients without signs or symptoms that are suggestive of
             CNS leukemia). Note: Patients with controlled CNS leukemia (documented by 2
             consecutive assessments of zero blast count in cerebrospinal fluid), and who are still
             receiving intrathecal (IT) therapy at study entry are considered eligible and will
             continue to receive IT therapy.

         17. Patients with immediately life-threatening, severe complications of leukemia such as
             uncontrolled bleeding, pneumonia with hypoxia or shock, or disseminated intravascular
             coagulation.

         18. Patients known to be refractory to platelet or packed red cell transfusions per
             institutional guidelines.

         19. Donor Lymphocyte Infusion within 30 days prior to first IO-202 administration.

         20. Current active treatment in another interventional therapeutic clinical study.

         21. Chronic systemic corticosteroid treatment with a dose of ≥10 mg prednisone/day or dose
             equivalent of another corticosteroid. Topical applications, inhaled sprays, eye drops,
             local injections of corticosteroids, and systemic steroids required for acute medical
             interventions are allowed.

         22. Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or
             investigational product administration or may interfere with the interpretation of
             study results and, in the judgment of the Investigator, would make the patient
             inappropriate for entry into this study.

         23. Acute Promyelocytic Leukemia patients or patients with known Philadelphia chromosome
             (Ph+) positive AML or chronic myelogenous leukemia (CML) blast crisis.

         24. Hyperleukocytosis (leukocytes ≥25 x 10e9/L) at first dose of IO-202. These patients
             may be treated with hydroxyurea or receive leukapheresis treatment according to
             routine practice, and enrolled in the study when the leukocyte count falls below 25 x
             10e9/L.

         25. Patients who are investigational site staff members or relatives of those site staff
             members or patients who are Immune-Onc employees directly involved in the conduct of
             the trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of IO-202 as measured by incidence of adverse events.
Time Frame:From first dose of IO-202 to 30 days following last study treatment
Safety Issue:
Description:Incidence of adverse events

Secondary Outcome Measures

Measure:To characterize the pharmacokinetics (PK) of IO-202 as defined by maximum plasma concentration (Cmax)
Time Frame:Through study completion, an average of 1 year
Safety Issue:
Description:Maximum concentration (Cmax) of IO-202
Measure:To characterize the PK of IO-202 as defined by area under the curve (AUC)
Time Frame:Through study completion, an average of 1 year
Safety Issue:
Description:measure area under the curve (AUC) of IO-202
Measure:To evaluate the incidence of anti-drug antibodies against IO-202
Time Frame:Through study completion, an average of 1 year
Safety Issue:
Description:Measure anti-drug antibodies in plasma.
Measure:To measure rates of response to IO-202 in patients with anti-drug antibodies
Time Frame:Through study completion, an average of 1 year
Safety Issue:
Description:Measure response rates in patients with anti-drug antibodies.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Immune-Onc Therapeutics Inc

Trial Keywords

  • Monocytic
  • Myelomonocytic

Last Updated

September 14, 2020