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AML With Monocytic DifferentiationPhase 1NCT04372433

IO-202 as Monotherapy and IO-202 Plus Azacitidine ± Venetoclax in Patients in AML and CMML

A Phase 1 study testing IO-202, IO-202 and Azacitidine and IO-202 and Azacitidine + Venetoclax in people with AML With Monocytic Differentiation and CMML, run by Immune-Onc Therapeutics at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To assess safety and tolerability at increasing dose levels of IO-202 in successive cohorts of participants with AML with monocytic differentiation and CMML in order to estimate the maximum tolerated dose (MTD) or maximum administered dose (MAD) and select the recommended Phase 2 dose (RP2D) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
AML With Monocytic Differentiation, CMML
What is being tested?
IO-202, IO-202 and Azacitidine and IO-202 and Azacitidine + Venetoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
67 participants
Where
14 sitesUnited States
Study dates
14 Sep 2020to 31 Jan 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must be ≥18.
  • For the Part 1 Dose-Escalation Phase, patients must be diagnosed with the following:
  • 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.
  • Relapsed or refractory CMML and has failed treatment with available therapies known to be active for CMML
  • Part 2 Expansion Phase:
  • Relapsed or refractory LILRB4high AML with myelomonocytic or monoblastic/monocytic differentiation and has failed treatment with available therapies known to be active for AML.
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  • Hypomethylating-agent naive CMML regardless of LILRB4 expression levels.
  • Newly diagnosed high LILRB4 expression monocytic AML patients considered to be ineligible for standard induction therapy.
  • Patients must be amenable to serial BM aspirates/biopsies and peripheral blood sampling during the study.
  • Patients must be able to understand and willing to sign an informed consent. A legally authorized representative may consent.
  • Patients must have an ECOG performance status of 0 to 2
  • Patients must have adequate hepatic function
  • Patients must have adequate renal function
  • 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 must be off systemic calcineurin inhibitors for at least 4 weeks prior to study drug treatment.
  • Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy.

Who cannot join

  • Patients who have previously received a monoclonal antibody therapy targeting LILRB4.
  • Patients who have undergone HSCT within 60 days of the first dose of IO-202.
  • 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.
  • Patients who received an investigational agent <7 days prior to their first day of study drug administration.
  • Patients for whom potentially curative anti-cancer therapy is available.
  • Patients who are pregnant or breastfeeding.
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  • Patients with uncontrolled, active infection.
  • Patients with known hypersensitivity to any of the components of the IO-202 formulation.
  • Patients with known pulmonary lesions and/or history of pneumonitis or interstitial lung disease.
  • Active known malignancy.
  • Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) or left ventricular ejection fraction (LVEF) <40%.
  • Ongoing cardiac dysrhythmias Grade 2 or higher per of NCI CTCAE, Version 5.0, Grade ≥2.
  • Known or suspected hypersensitivity to recombinant proteins.
  • Known active bacterial, viral, and/or fungal infection.
  • Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol.
  • Patients with clinical signs and/or symptoms suggesting active, uncontrolled central nervous system (CNS) leukemia or known active, uncontrolled CNS leukemia.
  • Patients with immediately life-threatening, severe complications of leukemia.
  • Donor Lymphocyte Infusion within 30 days prior to first IO-202 administration.
  • Current active treatment in another interventional therapeutic clinical study.
  • Chronic systemic corticosteroid treatment with a dose of >10 mg prednisone/day or dose equivalent.
  • 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.
  • Acute Promyelocytic Leukemia patients or patients with known Philadelphia chromosome (Ph+) positive AML or chronic myelogenous leukemia (CML) blast crisis.
  • Hyperleukocytosis (leukocytes ≥25 x 10e9/L) at first dose of IO-202.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Winship Cancer Institute of Emory University (105)

    Atlanta, Georgia, 30322

  • University of Colorado, Anschutz Medical Campus (103)

    Aurora, Colorado, 80045

  • The University of Chicago (113)

    Chicago, Illinois, 60637

  • Cleveland Clinic, Taussig Cancer Institute (111)

    Cleveland, Ohio, 44195

  • University of Texas Southwestern, Simmons Comprehensive Cancer Center (104)

    Dallas, Texas, 75390

  • University California, Davis (117)

    Davis, California, 95817

  • City of Hope (106)

    Duarte, California, 91010

  • MD Anderson Cancer Center (101)

    Houston, Texas, 77030

  • University of California, Irvine (107)

    Irvine, California, 92868

  • UCLA, Medical Center Division of Hematology/Oncology (119)

    Los Angeles, California, 90095

  • Weill Cornell Medical College, New York Presbyterian Hospital (110)

    New York, New York, 10021

  • Stanford University (114)

    Palo Alto, California, 94305

  • Oregon Health and Science University, Center for Hematologic Malignancies (116)

    Portland, Oregon, 97239

  • University of California, San Francisco (118)

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: A Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Intravenously Administered IO-202 and IO-202 + Azacitidine ± Venetoclax in Acute Myeloid Leukemia (AML) Patients With Monocytic Differentiation and in Chronic Myelomonocytic Leukemia (CMML) Patients

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

Read the detailed description

This is a Phase 1, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Intravenously Administered IO-202 and IO-202 + Azacitidine ± Venetoclax in Acute Myeloid Leukemia (AML) Patients with Monocytic Differentiation and in Chronic Myelomonocytic Leukemia (CMML) Patients

Being tested
IO-202, IO-202 and Azacitidine, IO-202 and Azacitidine + Venetoclax
Keywords
Monocytic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IO-202Biological

    IO-202 as monotherapy

  • IO-202 and AzacitidineBiological

    Also called IO-202 and AZA

    IO-202 and azacitidine combination therapy

  • IO-202 and Azacitidine + VenetoclaxBiological

    Also called IO-202 and AZA + Ven

    IO-202 and azacitidine + venetoclax combination therapy

  • IO-202 and AzacitidineBiological

    Also called IO-202 and AZA

    IO-202 and azacitidine combination therapy

Study groups in NCT04372433
Study groupRoleWhat they receive
Dose Escalation of IO-202ExperimentalDose cohorts treated with intravenous (IV) IO-202 monotherapy in ascending doses.
Receives: Biological: IO-202
Dose Escalation of IO-202 Plus AzacitidineExperimentalAZA Dose cohorts treated with intravenous (IV) IO-202 in ascending doses plus Azacitidine (IV or SC) on days 1-7 of each 28-day cycle.
Receives: Biological: IO-202 and Azacitidine
Dose Expansion of IO-202 plus Azacitidine AMLExperimentalTo enroll high LILRB4 expression monocytic AML patients refractory to or relapsed after available therapies known to be active in AML.
Receives: Biological: IO-202 and Azacitidine
Dose Expansion of IO-202 plus Azacitidine CMMLExperimentalTo enroll hypomethylating-agent naive CMML patients.
Receives: Biological: IO-202 and Azacitidine
Dose Expansion of IO-202 plus Azacitidine + Venetoclax (Ven)ExperimentalTo enroll newly diagnosed high LILRB4 expression AML patients who are unfit for intensive induction chemotherapy.
Receives: Biological: IO-202 and Azacitidine + Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence of adverse events.

    Incidence of adverse events

    Measured: From first dose of IO-202 to 30 days following last study treatment

  2. Safety of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence of adverse events.

    Severity of adverse events

    Measured: From first dose of IO-202 to 30 days following last study treatment

  3. Tolerability of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence and duration of dose interruptions and dose reductions of study treatment.

    Incidence dose interruptions and dose reductions

    Measured: From first dose of IO-202 to 30 days following last study treatment

Secondary outcomes (4)

  1. To characterize the pharmacokinetics (PK) of IO-202 and IO-202 plus azacitidine ± venetoclax and as defined by maximum plasma concentration (Cmax)

    Maximum concentration (Cmax) of IO-202

    Measured: Through study completion, an average of 1 year

  2. To characterize the PK of IO-202 and IO-202 IO-202 plus azacitidine ± venetoclax as defined by area under the curve (AUC)

    measure area under the curve (AUC) of IO-202

    Measured: Through study completion, an average of 1 year

  3. To evaluate the incidence of anti-drug antibodies against IO-202

    Measure anti-drug antibodies in plasma.

    Measured: Through study completion, an average of 1 year

  4. To measure rates of response to IO-202 and IO-202 plus azacitidine ± venetoclax

    Measure response rates in patients with anti-drug antibodies.

    Measured: Through study completion, an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2020
  2. Study start14 Sep 2020
  3. Primary completion31 Jan 2025
  4. Study completion31 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Dose Escalation and Expansion
Masking
None (open label)
Enrolment
67 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04372433
Sponsor's protocol ID
IO-202-CL-001
Status last verified
Feb 2025
First submitted
20 Apr 2020
Last updated
14 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Aribi A, Mannis GN, Madanat YF, Jonas BA, Dunavin N, Roboz GJ, Jeyakumar D, Garcia-Manero G, Liu H, Carraway HE, Saultz JN, Blum W, Schiller G, Huang T, Woodard P, Klencke B, Liao XC, Xiang H, Pollyea DA, DiNardo CD. A phase 1 study of IO-202, an anti-LILRB4 antibody, in chronic myelomonocytic leukemia and acute myeloid leukemia. Blood Neoplasia. 2025 Jun 9;2(4):100126. doi: 10.1016/j.bneo.2025.100126. eCollection 2025 Nov.

    PubMed 40919482

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing IO-202, IO-202 and Azacitidine and IO-202 and Azacitidine + Venetoclax in people with AML With Monocytic Differentiation and CMML, run by Immune-Onc Therapeutics at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of IO-202 and IO-202 plus azacitidine ± venetoclax as measured by incidence of adverse events. (time frame: From first dose of IO-202 to 30 days following last study treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04372433, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2025.

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