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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, 2021
Sponsor:
Collaborator:
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Immune-Onc Therapeutics Inc

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.

Condition or disease Intervention/treatment Phase
AML M5 AML M4 AML, Nos Acute Myelogenous Leukemia in Relapse Myelomonocytic Leukemia, Chronic Drug: IO-202 Dose Escalation Drug: IO-202 Dose Expansion Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose Escalation and Expansion
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : September 14, 2020
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : March 2024


Arm Intervention/treatment
Experimental: Dose Escalation
Dose cohorts treated with intravenous (IV) IO-202 monotherapy, in ascending doses Q2wks.
Drug: IO-202 Dose Escalation
IO-202 monotherapy

Experimental: Dose Expansion
IV IO-202 monotherapy at the recommended Phase 2 dose and frequency
Drug: IO-202 Dose Expansion
IO-202 monotherapy




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.

  4. 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.


Other Outcome Measures:
  1. 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

  2. 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

  3. 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



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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. Patients must be ≥18.
  2. For the Part 1 Dose-Escalation Phase, patients must be diagnosed with the following:

    1. Relapsed or refractory 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.
    2. Relapsed or refractory CMML and has failed treatment with available therapies known to be active for CMML
  3. Part 2 Expansion Phase:

    a) Relapsed or refractory AML with myelomonocytic or monoblastic/monocytic differentiation 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
  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 systemic 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); it may be initiated again if necessary 24 hours after 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. Active known malignancy with the exception of any of the following:

    1. Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer;
    2. Low-risk prostate cancer for which observation or hormonal therapy only is indicated;
    3. Any other malignancy treated with curative intent with the last treatment completed ≥6 months before study initiation (with the exception of hormonal therapies when indicated).
  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 or controlled atrial fibrillation are allowed.
  12. Ongoing cardiac dysrhythmias Grade 2 or higher per of NCI CTCAE, Version 5.0, Grade ≥2.
  13. Known or suspected hypersensitivity to recombinant human proteins.
  14. Known active bacterial, viral, and/or fungal infection including hepatitis B (HBV), hepatitis C, human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS)-related illness, or active Covid-19 infection. . Hepatitis B and C and HIV testing are not required for asymptomatic patients; however, for patients who have previously tested positive or have a known history of hepatitis B and C, HIV, and/or tuberculosis, clinical laboratory assessments at screening will include repeat testing for the previous infection. A sample for SARS-CoV-2 should be obtained during the screening period, and results must be available prior to C1D1.
  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. Donor Lymphocyte Infusion within 30 days prior to first IO-202 administration.
  19. Current active treatment in another interventional therapeutic clinical study.
  20. 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.
  21. 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.
  22. Acute Promyelocytic Leukemia patients or patients with known Philadelphia chromosome (Ph+) positive AML or chronic myelogenous leukemia (CML) blast crisis.
  23. 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.
  24. 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.

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): NCT04372433


Contacts
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Contact: Paul Woodard, MD 650-457-1741 ext 105 paul.woodard@immuneonc.com
Contact: Liz Wieland elizabeth.wieland@immuneonc.com

Locations
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United States, California
University California, Davis Recruiting
Davis, California, United States, 95817
Principal Investigator: Brian Jonas, MD         
City of Hope Recruiting
Duarte, California, United States, 91010
Principal Investigator: Ahmed Aribi, MD         
University of California, Irvine Recruiting
Irvine, California, United States, 92868
Contact: Stephanie Osorio       ucstudy@uci.edu   
Principal Investigator: Deepa Jeyakumar, MD         
United States, Colorado
University of Colorado, Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Chase Conrad, BS    720-848-8033      
Principal Investigator: Daniel Pollyea, MD, MS         
United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Shannon Gleason, MLS    404-778-4334 ext 10808    shannon.gleason@emory.edu   
Principal Investigator: William Blum, MD         
United States, Illinois
The University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Howie Weiner    773-702-2084      
Principal Investigator: Hongtao Liu, MD         
United States, New York
Weill Cornell Medical College, New York Presbyterian Hospital Recruiting
New York, New York, United States, 10021
Contact: Yulia Dault    212-746-4829    yud9001@med.cornell.edu   
Principal Investigator: Gail Roboz, MD         
United States, Texas
University of Texas Southwestern, Simmons Comprehensive Cancer Center Recruiting
Dallas, Texas, United States, 75390
Contact: Prapti Patel, MD       prapti.patel@utsouthwestern.edu   
Principal Investigator: Prapti Patel, MD         
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Courtney DiNardo, MD    713-794-1141      
Principal Investigator: Courtney DiNardo, MD         
Sponsors and Collaborators
Immune-Onc Therapeutics Inc
California Institute for Regenerative Medicine (CIRM)
Investigators
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Study Director: Paul Woodard, MD Immune-Onc Therapeutics
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Responsible Party: Immune-Onc Therapeutics Inc
ClinicalTrials.gov Identifier: NCT04372433    
Other Study ID Numbers: IO-202-CL-001
First Posted: May 4, 2020    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: September 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
Keywords provided by Immune-Onc Therapeutics Inc:
Monocytic
Myelomonocytic
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases