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IO-202 as Monotherapy in Patients in AML and CMML

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ClinicalTrials.gov Identifier: NCT04372433
Recruitment Status : Recruiting
First Posted : May 4, 2020
Last Update Posted : September 16, 2020
Sponsor:
Information provided by (Responsible Party):
Immune-Onc Therapeutics Inc

Tracking Information
First Submitted Date  ICMJE April 20, 2020
First Posted Date  ICMJE May 4, 2020
Last Update Posted Date September 16, 2020
Actual Study Start Date  ICMJE September 14, 2020
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2020)
  • 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 ]
    Incidence of adverse events
  • Safety of IO-202 as measured by severity of adverse events. [ Time Frame: From first dose of IO-202 to 30 days following last study treatment ]
    Severity of adverse events
  • Tolerability of IO-202 as measured by incidence and duration of dose interruptions and dose reductions of study treatment [ Time Frame: From first dose of IO-202 to 30 days following last study treatment ]
    Incidence dose interruptions and dose reductions
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2020)
  • 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 ]
    Maximum concentration (Cmax) of IO-202
  • 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 ]
    measure area under the curve (AUC) of IO-202
  • To evaluate the incidence of anti-drug antibodies against IO-202 [ Time Frame: Through study completion, an average of 1 year ]
    Measure anti-drug antibodies in plasma.
  • To measure rates of response to IO-202 in patients with anti-drug antibodies [ Time Frame: Through study completion, an average of 1 year ]
    Measure response rates in patients with anti-drug antibodies.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2020)
  • 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 ]
    Maximum concentration (Cmax) of IO-202
  • 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 ]
    measure area under the curve (AUC) of IO-202
  • To evaluate the incidence of anti-drug antibodies against IO-202 [ Time Frame: Through study completion, an average of 1 year ]
    Measure anti-drug antibodies in plasma.
  • To measure rates of response to IO-202 in patients with anti-drug antibodies [ Time Frame: Through study completion, an average of 1 year ]
    Measure response rates in patients with anti-drug antibodies.
  • Measure response rates in patients treated with IO-202 or IO-202 in combination with AZA [ Time Frame: Through study completion, an average of 1 year ]
    Measure response rates by bone marrow examination of blast percentage.
Current Other Pre-specified Outcome Measures
 (submitted: September 14, 2020)
  • To correlate target expression with response rates [ Time Frame: Through study completion, a average of 1 year ]
    Statistical correlation levels of target expression on leukemic blasts with response rate
  • To correlate target expression with rates of adverse events [ Time Frame: Through study completion, a average of 1 year ]
    Statistical correlation of target expression on leukemic blasts with adverse event rates
  • To evaluate immunophenotype of leukemic blasts after study treatment. [ Time Frame: Through study completion, a average of 1 year ]
    Measure immunophenotype of leukemic blasts from bone marrow aspirates after study treatment
Original Other Pre-specified Outcome Measures
 (submitted: April 29, 2020)
  • To assess changes in lymphocytes with IO-202 or IO-202 in combination with AZA [ Time Frame: Through study completion, a average of 1 year ]
    Measure changes in numbers of lymphocytes with study drug treatment
  • To measure blood immune proteins with IO-202 or IO-202 in combination with AZA [ Time Frame: Through study completion, a average of 1 year ]
    Measure changes in blood immune proteins with study drug treatment
  • To correlate target expression with response rates [ Time Frame: Through study completion, a average of 1 year ]
    Statistical correlation levels of target expression on leukemic blasts with response rate
  • To correlate target expression with rates of adverse events [ Time Frame: Through study completion, a average of 1 year ]
    Statistical correlation of target expression on leukemic blasts with adverse event rates
  • To evaluate immunophenotype of leukemic blasts after study treatment. [ Time Frame: Through study completion, a average of 1 year ]
    Measure immunophenotype of leukemic blasts from bone marrow aspirates after study treatment
 
Descriptive Information
Brief Title  ICMJE IO-202 as Monotherapy in Patients in AML and CMML
Official Title  ICMJE 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)
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Dose Escalation and Expansion
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • AML M5
  • AML M4
  • AML, Nos
  • Acute Myelogenous Leukemia in Relapse
  • Myelomonocytic Leukemia, Chronic
Intervention  ICMJE
  • Drug: IO-202 Dose Escalation
    IO-202 monotherapy
  • Drug: IO-202 Dose Expansion
    IO-202 monotherapy
Study Arms  ICMJE
  • Experimental: Dose Escalation
    Dose cohorts treated with intravenous (IV) IO-202 monotherapy, in ascending doses Q2wks.
    Intervention: Drug: IO-202 Dose Escalation
  • Experimental: Dose Expansion
    IV IO-202 monotherapy at the recommended Phase 2 dose and frequency
    Intervention: Drug: IO-202 Dose Expansion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 14, 2020)
44
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2020)
64
Estimated Study Completion Date  ICMJE March 2024
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Paul Woodard, MD 650-457-1741 ext 105 paul.woodard@immuneonc.com
Contact: Liz Wieland elizabeth.wieland@immuneonc.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04372433
Other Study ID Numbers  ICMJE IO-202-CL-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Immune-Onc Therapeutics Inc
Study Sponsor  ICMJE Immune-Onc Therapeutics Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Paul Woodard, MD Immune-Onc Therapeutics
PRS Account Immune-Onc Therapeutics Inc
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP