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AzTrials

Acute Myeloid LeukemiaPhase 1/2NCT04086264

IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia

A Phase 1/2 study testing Azacitidine, IMGN632 and Venetoclax in people with Acute Myeloid Leukemia, run by AbbVie at 29 sites in 6 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is an open-label, multicenter, Phase 1b/2 study to determine the safety and tolerability of IMGN632 and assess the antileukemia activity of IMGN632 when administered in combination with azacitidine and/or venetoclax in participants with relapsed and frontline CD123-positive AML. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Azacitidine, IMGN632 and Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
218 participants
Where
29 sitesin 6 countries
Study dates
6 Nov 2019to Feb 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Patient must be ≥ 18 years of age.
  • Patients must have confirmed diagnosis of AML (excluding acute promyelocytic leukemia) based on World Health Organization classification (Arber 2016).
  • Disease characteristics and allowable prior therapy:
  • Patients must be evaluated for any available standard of care therapies (including induction, consolidation chemotherapy and/or transplant) and, in the opinion of the treating physician, be deemed appropriate for this experimental therapy.
  • Treatment-naïve (untreated) patients will be allowed in the Expansion Phase for Regimen C (Triplet) (IMGN632 + azacitidine + venetoclax). No prior treatments with hypomethylating agents (HMAs) for MDS are allowed.
  • Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry [IHC]).
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  • Patients may have received prior CD123-targeted therapies, except IMGN632, as long as CD123 remains detectable during screening.
  • Relapsed or refractory CD123-positive AML patients will be allowed to enroll in the Escalation Phase of Regimens A, B, and C (Triplet (IMGN632 + azacitidine, venetoclax, or azacitidine + venetoclax, respectively) and relapsed CD123-positive AML patients will be allowed to enroll the Expansion Phase of Regimens A-C. Note: Patients may also have received up to 2 prior lines of therapy, eg, frontline treatment (induction, consolidation [including transplant], and maintenance) and 1 salvage regimen.
  • Patients enrolling in Regimen D must be in CR (CR/CRh/CRp/ CRi) and be MRD+ at the time of screening, confirmed by central laboratory testing. Patients may have no more than 2 prior lines of therapy (which may include stem cell transplant), ie, frontline or first salvage. Note: Fit patients who received intensive treatment (eg 3+7, HiDAC) are eligible for Regimen D Cohort D1. Unfit patients who received non-intensive treatment (eg, HMA, low dose cytarabine) are eligible for Regimen D Cohort D2.
  • Previous treatment-related toxicities must have resolved to Grade 1 or baseline (excluding alopecia).
  • For patients enrolling in Regimens A-D, total WBC count must < 25 × 10^9 cells/L. Hydroxyurea may be used to control blood counts before Cycle 1 Day 1, at the discretion of the treating physician, according to institutional practice. During the Escalation Phase in Regimens A-C, hydroxyurea may also be used during Cycle 1.
  • Liver enzymes (AST and ALT) ≤ 3 × the upper limit of normal (ULN).
  • Total bilirubin ≤ 1.5 × the ULN; patients with Gilbert syndrome must have total bilirubin < 3.0 × ULN with direct bilirubin < 1.0 × ULN at the time of enrollment.
  • An estimated glomerular filtration rate (eGFR) of > 30 mL/min/1.73 m2 or creatinine clearance of > 30 mL/min.
  • Left ventricular ejection fraction (LVEF) ≥ 45% for patients enrolling in Regimens A-D based on locally available assessment, eg, echocardiogram or other modality.
  • Patients with prior autologous or allogeneic bone marrow transplant are eligible. Patients with an allogeneic transplant must meet the following conditions: The transplant must have been performed more than 120 days before the date of dosing on this study, the patient must not have active ≥ Grade 2 graft versus host disease (GvHD), or extensive chronic GvHD of any severity, and must be off all immunosuppression for at least 2 weeks prior to first dose of IMGN632.
  • Participants or their legally authorized representative must voluntarily sign and date an informed consent, approved by an Institutional Review Board/Independent Ethics Committee (IRB/IEC), before performance of any study-related procedure not part of normal medical care.
  • Women of childbearing potential (WCBP), defined as sexually mature women who have not undergone surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months (ie, who have had menses any time in the preceding 12 consecutive months), must agree to use acceptable contraceptive methods while on study drug and for at least 7 months after the last dose of IMGN632.
  • WCBP must have a negative pregnancy test within 3 days before the first dose of study drug.
  • Male patients who are able to father children must agree to use acceptable methods of contraception throughout the study and for at least 4 months after the last dose of study drug(s).
  • Patients with prior malignancy are eligible; however, the patient's malignancy must be well-controlled or stable and have completed all systemic chemotherapy and radiotherapy for the prior malignancy at least 6 months before enrollment, and all treatment-related toxicities must have resolved to ≤ Grade 1 (excluding alopecia). Note: patients with prostate cancer or breast cancer on adjuvant hormonal therapy are eligible and may or may not be on long-term maintenance treatment that is unlikely to interfere with study therapy. Note: patients with tumors with a negligible risk for metastasis or death (eg, adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible.
  • Patients in expansion Cohorts C1 and C2 must be considered ineligible for intensive induction therapy defined by the following:
  • ≥ 75 years of age OR
  • < 75 years of age with at least one of the following co-morbidities documented within 28 days of Cycle 1 Day 1:
  • ECOG performance status of 2 or 3
  • History of congestive heart failure requirement treatment or ejection fraction ≤ 50% or chronic stable angina
  • Diffusing capacity of the lung for carbon monoxide ≤ 65% or forced expiratory volume in 1 second ≤ 65%
  • Creatinine clearance ≥ 30 mL/min to < 45 mL/min
  • Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × ULN
  • Patients in Cohort C1 and C2 must have an ECOG performance status of 0 to 2 for those ≥ 75 years of age OR 0 to 3 for < 75 years of age.
  • Patients must not be incarcerated and must be freely willing and able to provide informed consent. Examples of patients unable to freely provide informed consent may include some adults under legal protection measure (eg, under guardianship/curatorship) or unable to express their consent and select adults under psychiatric care. Investigator's discretion should be applied.

Who cannot join

  • Patients who have received any anticancer therapy, including investigational agents, within 14 days (or within 28 days for checkpoint inhibitors) before drug administration on this study (hydroxyurea is allowed before beginning study treatment). Patients must have recovered to baseline from all acute toxicity from this prior therapy.
  • Patients who have been previously treated with IMGN632.
  • Patients with myeloproliferative neoplasm-related secondary AML are excluded from the Dose Expansion Phase of the study.
  • Patients with active central nervous system (CNS) AML will be excluded. A lumbar puncture does not need to be performed unless there is clinical suspicion of CNS involvement per investigator judgement. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS AML is allowed with the approval of the sponsor.
  • Patients with a history of sinusoidal obstruction syndrome/venous occlusive disease of the liver.
  • Myocardial infarction within 6 months before enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities before study entry.
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  • Clinically relevant active infection including known active hepatitis B or C, HIV infection, or cytomegalovirus or any other known concurrent infectious disease that, in the judgment of the investigator, would make a patient inappropriate for enrollment into this study (testing not required).
  • Patients who have undergone a major surgery within 4 weeks (or longer if not fully recovered) before study enrollment.
  • Serious or poorly controlled medical conditions that could be exacerbated by treatment or that would seriously compromise safety assessment or compliance with the protocol, in the judgment of the investigator.
  • Women who are pregnant or breastfeeding
  • Prior known hypersensitivity reactions to monoclonal antibodies (≥ Grade 3).
  • Prior known hypersensitivity reactions to study drugs and/or any of their excipients.
  • Patients who have a history of allergy to IMGN632 (or any of its excipients), azacitidine, or venetoclax.

Trial locations and contacts

29 sites in 6 countries.

29 sites in 6 countries

United States13 sites

  • University of Michigan /ID# 269079

    Ann Arbor, Michigan, 48109-2800

  • Dana-Farber Cancer Institute /ID# 269267

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute /ID# 269266

    Buffalo, New York, 14263

  • Northwestern University- Robert H. Lurie Comprehensive Cancer Center /ID# 269642

    Chicago, Illinois, 60611-3015

  • Cleveland Clinic - Cleveland /ID# 269272

    Cleveland, Ohio, 44195

  • City of Hope National Medical Center /ID# 269273

    Duarte, California, 91010

  • Duke University Health System /ID# 269268

    Durham, North Carolina, 27705-3976

  • MD Anderson Houston /ID# 269265

    Houston, Texas, 77030-4000

  • New York Presbyterian Hospital Weill Cornell Medical Center /ID# 269271

    New York, New York, 10461

  • University Of California Irvine Medical Center /ID# 269275

    Orange, California, 92868

  • Mayo Clinic Hospital Rochester /ID# 269643

    Rochester, Minnesota, 55905

  • Fred Hutchinson Cancer Research Center /ID# 269270

    Seattle, Washington, 98109

  • Moffitt Cancer Center /ID# 269269

    Tampa, Florida, 33612

Other trials in United States

France6 sites

  • Centre Hospitalier de Versailles André Mignot /ID# 269287

    Le Chesnay, 78157

  • Institut Paoli-Calmettes /ID# 269080

    Marseille, Bouches-du-Rhone, 13273

  • Centre Antoine-Lacassagne /ID# 269285

    Nice, Provence-Alpes-Côte d'Azur Region, 06189

  • Hôpital Saint-Louis /ID# 269282

    Paris, Paris, 75010

  • Hospices Civils de Lyon - Centre Hospitalier Lyon-Sud /ID# 269286

    Pierre-Bénite, Rhone, 69310

  • IUCT Oncopole /ID# 269284

    Toulouse, Occitanie, 31059

Other trials in France

Italy4 sites

  • IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 269281

    Bologna, Bologna, 40138

  • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST - IRCCS /ID# 269279

    Meldola, Reggio Emilia, 47014

  • Istituto Europeo Di Oncologia /ID# 269646

    Milan, Milano, 20141

  • Azienda Ospedaliero Universitaria Maggiore Della Carità /ID# 269280

    Novara, Novara, 28100

Other trials in Italy

Germany3 sites

  • Universitaetsklinikum Leipzig /ID# 269682

    Leipzig, Saxony, 04103

  • Universitaetsklinikum Muenster /ID# 269688

    Münster, North Rhine-Westphalia, 48149

  • Universitaetsklinikum Ulm /ID# 269686

    Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

Spain2 sites

  • Hospital MD Anderson Cancer Center Madrid /ID# 269641

    Madrid, Madrid, 28033

  • Hospital Universitario y Politecnico La Fe /ID# 269278

    Valencia, Valencia, 46026

Other trials in Spain

United Kingdom1 site

  • Oxford University Hospital NHS Trust /ID# 269647

    Oxford, Oxfordshire, OX3 7LE

Other trials in United Kingdom

About this study

Official title: A Phase 1b/2 Study of IMGN632 as Monotherapy or Combination With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia

This is an open-label, multicenter, Phase 1b/2 study to determine the safety and tolerability of IMGN632 and assess the antileukemia activity of IMGN632 when administered in combination with azacitidine and/or venetoclax in participants with relapsed and frontline CD123-positive AML.

Read the detailed description

This study explores multiple IMGN632 doses in combination and monotherapy Regimens, including (A - closed to enrollment)) azacitidine, (B-closed to enrollment) venetoclax, (C) azacitidine+venetoclax, and (D- closed to enrollment) monotherapy in MRD+ AML. For combination Regimens A-C, a Phase 1b Dose Escalation Cohort will determine the recommended Phase 2 dose (RP2D) of IMGN632 in that specific combination Regimen, followed by a Phase 2 Dose Expansion Cohort for each combination Regimen to characterize the safety profile further and assess the antileukemia activity of the different combination Regimens.

Being tested
Azacitidine, IMGN632, Venetoclax
Keywords
Acute Myeloid Leukemia, AML, Minimal detectable disease, MRD, CD123, Relapsed/refractory, Frontline
Medical subject headings
Leukemia, Myeloid, Acute, Recurrence

What participants receive

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

  • AzacitidineDrug

    Also called Vidaza, Decitabine

    Commercially available formulation given subcutaneously (SC) or intravenous (IV)

  • IMGN632Drug

    Also called CD123-targeted ADC

    Study formulation given intravenously (IV)

  • VenetoclaxDrug

    Also called Venclexta, Venclyxto

    Commercially available formulation administered orally

Study groups in NCT04086264
Study groupRoleWhat they receive
Regimen A (Closed to Enrollment)ExperimentalIMGN632, administered intravenously on Day 7 of a 28 day cycle at 0.015 mg/kg, 0.045 mg/kg, or 0.09 mg/kg, in combination with azacitidine, administered subcutaneously or intravenously daily at 75 mg/m2 on Days 1 to 7 of a 28 day cycle. Cycle 1 azacitidine dose in subsequent cohorts may be reduced.
Receives: Drug: Azacitidine; Drug: IMGN632
Regimen B (Closed to Enrollment)ExperimentalIMGN632, administered intravenously on Day 7 of a 21 day cycle at 0.015 mg/kg, 0.045 mg/kg, or 0.09 mg/kg, in combination with venetoclax, administered orally daily at 100 mg on Day 1, 200mg on Day 2, and 400 mg on the day 3 up to Day 21 of a 21 day cycle. Alternate schedules with reduced venetoclax administration may be explored.
Receives: Drug: IMGN632; Drug: Venetoclax
Regimen C-Frontline&Relapsed/Refractory(Closed to Enrollment)ExperimentalIMGN632, administered intravenously on Day 7 of a 28 day cycle at 0.015 mg/kg or 0.045 mg/ kg, in combination with azacitidine, administered subcutaneously or intravenously daily at 35-75 mg/ m2 given for Days 1 to 7 of a 28 day cycle and venetoclax, administered orally daily at 100 mg on Day 1, 200mg on Day 2, and 400 mg on Day 3 up to Day 28 of a 28 day cycle. Alternate schedules with reduced venetoclax administration or reduced azacitidine dose or administration may be explored.
Receives: Drug: Azacitidine; Drug: IMGN632; Drug: Venetoclax
Regimen D (Closed to Enrollment)ExperimentalIMGN632, administered intravenously on Day 1 of a 21 day cycle at 0.045 mg/kg, as a monotherapy for Fit and Unfit MRD+ patients.
Receives: Drug: IMGN632

What is being measured

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

  1. Safety and Tolerability

    Evaluate the safety and tolerability and identify an RP2D of IMGN632 when administered in combination with azacitidine, with venetoclax, and with azacitidine and venetoclax in patients with relapsed or refractory CD123-positive AML through review of Treatment Emergent Adverse Events and abnormal laboratory values that result in a failure to meet the criteria for re-treatment.

    Measured: approximately 3 years

  2. Preliminary antileukemia activity

    Assess preliminary antileukemia activity of IMGN632 when administered as a monotherapy in MRD+ Fit and MRD + Unfit AML patient populations, and in combination with azacitidine, with venetoclax, and with azacitidine and venetoclax in patients with relapsed or untreated AML as assessed by complete response, complete remission with partial hematologic recovery, complete remission with incomplete platelet recovery, morphologic leukemia-free state, partial response, and duration of remission.

    Measured: approximately 20 months

  3. Minimal Residual Disease Levels

    Assess Minimal Residual Disease Levels using central flow cytometry-based testing.

    Measured: approximately 18 months

Secondary outcomes (4)

  1. Number of Participants with Treatment-Emergent Adverse Events (TEAEs) (Dose Expansion Phase)

    Measured: Up to approximately 12 months

  2. Study Drug Concentration (Dose Escalation and Expansion)

    Measured: Up to approximately 12 months

  3. Anti-drug Antibody Concentration (Dose Escalation and Expansion)

    Measured: Up to approximately 12 months

  4. Minimal Residual Disease Levels (Dose Escalation)

    Measured: Up to approximately 7 months

Timeline

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

  1. First posted11 Sep 2019
  2. Study start6 Nov 2019
  3. Primary completionFeb 2027 (estimated)
  4. Study completionFeb 2027 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
218 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04086264
Sponsor's protocol ID
IMGN632-0802
Other IDs
2024-514197-50-00
Status last verified
Aug 2025
First submitted
9 Sep 2019
Last updated
14 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Azacitidine, IMGN632 and Venetoclax in people with Acute Myeloid Leukemia, run by AbbVie at 29 sites in 6 countries.

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 31 inclusion and 13 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: under way, not looking for participants, as of the sponsor's last update on 14 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States, France, Italy, Germany, Spain and 1 more country. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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 and Tolerability (time frame: approximately 3 years). 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 NCT04086264.

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 Aug 2025.

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