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Trial record 1 of 1 for:    IO-202
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IO-202 as Monotherapy and in Combination With Azacitidine in AML and CMML

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ClinicalTrials.gov Identifier: NCT04372433
Recruitment Status : Not yet recruiting
First Posted : May 4, 2020
Last Update Posted : May 4, 2020
Sponsor:
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 and in combination with azacitidine (AZA).

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 A Drug: IO-202 Dose Expansion B 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 and in Combination with Azacitidine 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 : 64 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 I Study of IO-202 as Monotherapy and in Combination With Azacitidine in Relapsed/ Refractory AML With Monocytic Differentiation and in Relapsed/Refractory CMML
Estimated Study Start Date : July 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, followed by IO-202 Q2wks at the same dose in combination with IV or subcutaneous (SC) azacitidine (75mg/m2) for 7 days every 28 days
Drug: IO-202 Dose Escalation
IO-202 monotherapy and in combination with azacitidine
Other Names:
  • Azacitidine
  • Vidaza

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

Experimental: Dose Expansion B
IV IO-202 Q2wks at the recommended Phase 2 dose and frequency in combination with IV or SC azacitidine, 75mg/m2 for 7 days every 28 days
Drug: IO-202 Dose Expansion B
IO-202 in combination with azacitidine
Other Names:
  • Azacitidine
  • Vidaza




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.

  5. 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.


Other Outcome Measures:
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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:

    a) Relapsed AML with myelomonocytic or monoblastic/monocytic differentiation according to the World Health Organization (WHO) 2016 criteria and fulfills one of the following: i) Primary refractory to intensive induction chemotherapy, defined as lack of complete remission (CR), or complete remission with incomplete hematologic recovery (CRi) after >2 cycles of intensive induction chemotherapy ii) Primary refractory to low-intensity treatment for patients ineligible for an intensive induction therapy, defined as lack of CR/CRi after >2 cycles of low-intensity therapy iii) Progression on therapy iv) Relapsed after achieving CR/CRi with intensive induction chemotherapy v) Relapsed after achieving CR/CRi with low-intensity treatment

    b) CMML according to WHO 2016 criteria and fulfills one of the following: i) Primary refractory defined as lack of response to at least 4 cycles of a hypomethylating agent. Lack of response is defined as lack of CR, complete cytogenetic remission, partial remission (PR), marrow response, or clinical benefit.

    ii) Progression on therapy iii) Relapsed after achieving a response to a hypomethylating agent.

  3. For the Part 2 Expansion Phase, Arms A and B, patients must be diagnosed with the following:

    a) AML with myelomonocytic or monoblastic/monocytic differentiation according to the World

    Health Organization 2016 criteria and fulfills one of the following:

    i) Primary refractory to venetoclax + AZA, defined as lack of CR/CRi after ≥2 cycles of low intensity therapy ii) Progression on therapy iii) Relapsed after achieving CR/CRi with venetoclax + AZA

  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. More than 2 prior lines of AML or CMML therapy (prior therapy for myelodysplastic syndrome [MDS] if AML has transformed from prior MDS, does not count towards lines of therapy for AML).
  4. 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 [Day -14]).
  5. 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.
  6. Patients for whom potentially curative anti-cancer therapy is available.
  7. Patients who are pregnant or breast feeding.
  8. Patients with uncontrolled, active infection.
  9. Patients with known hypersensitivity to any of the components of the IO-202 formulation.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. Known or suspected hypersensitivity to recombinant human proteins.
  15. 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.
  16. 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.
  17. 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.
  18. Patients with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, or disseminated intravascular coagulation.
  19. Patients known to be refractory to platelet or packed red cell transfusions per institutional guidelines.
  20. Donor Lymphocyte Infusion within 30 days prior to first IO-202 administration.
  21. Current active treatment in another interventional therapeutic clinical study.
  22. 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.
  23. 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.
  24. Acute Promyelocytic Leukemia patients or patients with known Philadelphia chromosome (Ph+) positive AML or chronic myelogenous leukemia (CML) blast crisis.
  25. Hyperleukocytosis (leukocytes ≥30 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 30 x 10e9/L.
  26. 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 1-650-457-1741 ext 105 paul.woodard@immuneonc.com

Sponsors and Collaborators
Immune-Onc Therapeutics Inc
Investigators
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Study Director: Medical Director, MD Immune-Onc Therapeutics Inc
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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: May 4, 2020
Last Verified: April 2020
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, Myeloid, Acute
Leukemia, Myelomonocytic, Chronic
Neoplasms by Histologic Type
Neoplasms
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors