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Acute Myeloid LeukemiaPhase 1NCT03900949

Gentuzumab Ozogamicin and Midostaurin Combination With Standard Cytarabine and Danunorubi Midostaurin as a Novel Approach to Treating Patients With Newly Diagnosed FLT-3 Mutated Acute Myeloid Leukemia

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cytarabine and Daunorubicin Hydrochloride in people with Acute Myeloid Leukemia, run by Uma Borate at 2 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

This phase I study hopes to explore how safe and tolerable is the combination of gemtuzumab ozogamicin (GO) and midostaurin, with the standard induction therapy (cytarabine and daunorubicin) in patients with newly diagnosed FLT-3 mutated Acute Myeloid Leukemia (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?
Allogeneic Hematopoietic Stem Cell Transplantation, Cytarabine and Daunorubicin Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
2 sitesUnited States
Study dates
13 Mar 2019to 23 Oct 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

  • Ability to understand and the willingness to sign a written informed consent document
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Newly diagnosed AML as confirmed by bone marrow and/or peripheral blood examination as indicated, with:
  • Confirmed CD33 positivity, per institutional standards
  • Presence of FLT3 internal tandem duplication (ITD) or tyrosine kinase domain (TKD) mutation as confirmed by next-generation sequencing (NGS) or other molecular method
  • Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN; local laboratory)
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  • Alanine aminotransferase (ALT) < 2.5 x ULN
  • Total bilirubin < 2 x ULN (except for patients with known Gilbert's syndrome)
  • Calculated creatinine clearance (according to the Cockcroft-Gault equation) > 40 mL/min OR serum creatinine < 1.5 x the ULN
  • Female patients of childbearing potential must agree to use adequate contraception (2 forms of contraception or abstinence) from the screening visit until 6 months following the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 4 months following the last dose of study treatment. They must also refrain from sperm donation from the screening visit until 4 months following the last dose of study treatment

Who cannot join

  • Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement to enter study)
  • Acute promyelocytic leukemia (per World Health Organization classification)
  • Active central nervous system (CNS) involvement by AML, as assessed at discretion of principal investigator (PI) or treating physician and confirmed by lumbar puncture
  • Except for hydroxyurea, no other prior systemic anti-AML therapies may have been received prior to starting study therapy
  • Known history of veno-occlusive disease
  • Known active human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection
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  • Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled ventricular arrhythmias
  • Patients with uncontrolled infection will not be enrolled until infection is treated
  • Any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
  • Inability to take oral medication
  • Hypersensitivity to any study agent, or its excipients, when administered alone
  • Pregnancy or breastfeeding at the time of enrollment

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Oregon Health and Science University Knight Cancer Institute - Northwest Portland

    Portland, Oregon, 97210

Other trials in United States

About this study

Official title: A Phase I Study to Evaluate the Safety and Tolerability of Gemtuzumab Ozogamicin and Midostaurin When Used in Combination With Standard Cytarabine and Daunorubicin Induction for Newly Diagnosed FLT3-mutated Acute Myeloid Leukemia

This phase I study hopes to explore how safe and tolerable is the combination of gemtuzumab ozogamicin (GO) and midostaurin, with the standard induction therapy (cytarabine and daunorubicin) in patients with newly diagnosed FLT-3 mutated Acute Myeloid Leukemia (AML). GO is FDA approved for the treatment of adults with newly diagnosed CD33 positive AML and used in combination with chemotherapy, cytarabine and daunorubicin. Midostaurin is FDA approved for use with cytarabine and daunorubicin in patients with FLT3-mutated AML. By combining standard induction therapy with GO and midostaurin, our aim is to investigate a novel approach to treating patients with newly diagnosed FLT3-mutated AML.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the maximum tolerated dose (MTD) of combining gemtuzumab ozogamicin (GO) to the induction regimen of cytarabine and daunorubicin (DA) and midostaurin.

SECONDARY OBJECTIVES:

  1. To assess the frequency of early death associated with study treatment. II. To evaluate the preliminary efficacy of the study treatment. III. To assess the safety profile of the study treatment.

EXPLORATORY OBJECTIVES:

  1. Quantify CD33 expression on acute myeloid leukemia (AML) blasts. II. Determine the CD33 single-nucleotide polymorphism (SNP) status previously reported to correlate with response and correlate clinical outcomes of patients with the CD33 genotype.

OUTLINE: This is a dose finding study to identify the maximum tolerated dose (MTD) schedule of GO, and its safety and tolerability in combination with midostaurin in FLT3-mutated newly diagnosed AML patients.

INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7, daunorubicin IV on days 1-3 and midostaurin 50mg orally (PO) twice daily (BID) on days 8-21. Patients also receive gemtuzumab ozogamicin IV either on day or days 1 and 4 or days 1, 4 and 7 depending on dose level in the absence of disease progression or unacceptable toxicity.

RE-INDUCTION THERAPY: Between days 14 and 21 of Induction Therapy, patients who achieve at least 5% bone marrow blasts after an optional bone marrow biopsy may receive a single 28-day cycle of cytarabine and daunorubicin with or without midostaurin per the treating physician. Patients who achieve a complete remission (CR) or complete remission with incomplete blood count recovery (CRi) may undergo allogeneic stem cell transplantation (SCT) or receive consolidation therapy.

CONSOLIDATION THERAPY:

PATIENTS < 60 YEARS: Patients receive high dose cytarabine (HiDAC) IV on days 1, 3, and 5 and gemtuzumab ozogamicin IV on day 1 of cycle 1 and midostaurin 50mg PO BID on days 8-21. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

PATIENTS >= 60 YEARS: Patients receive cytarabine (MiDAC) IV on days 1, 3, and 5 and gemtuzumab ozogamicin IV on day 1 of cycle 1 and midostaurin 50mg PO BID on days 8-21. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 24 months.

Being tested
Allogeneic Hematopoietic Stem Cell Transplantation, Cytarabine, Daunorubicin Hydrochloride, Gemtuzumab Ozogamicin, Midostaurin
Keywords
FLT, FLT-3, Acute Myeloid Leukemia
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC

    Undergo allogeneic SCT

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IV

  • Daunorubicin HydrochlorideDrug

    Also called Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin

    Given IV

  • Gemtuzumab OzogamicinDrug

    Also called Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab

    Given IV

  • MidostaurinDrug

    Also called CGP 41251, CGP41251, N-Benzoyl-Staurosporine, N-Benzoylstaurosporine

    Given PO

Study groups in NCT03900949
Study groupRoleWhat they receive
Treatment (gemtuzumab ozogamicin, cytarabine, daunorubicin)ExperimentalINDUCTION THERAPY: Cytarabine intravenously (IV) on days 1-7, daunorubicin IV on days 1-3 and midostaurin 50 mg orally (PO) twice daily (BID) on days 8-21. Gemtuzumab ozogamicin IV may be given either on days 1, or days 1 and 4 or days 1, 4 and 7. RE-INDUCTION THERAPY: Between days 14 and 21 of Induction Therapy, patients may receive a single 28-day cycle of cytarabine and daunorubicin with or without midostaurin per the treating physician. Patients may also undergo allogeneic stem cell transplantation (SCT) or receive consolidation therapy. CONSOLIDATION THERAPY: PATIENTS < 60 YEARS: high dose cytarabine (HiDAC) IV on days 1, 3, and 5 and gemtuzumab ozogamicin IV on day 1 of cycle 1 and midostaurin 50 mg PO BID on days 8-21. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. PATIENTS >= 60 YEARS: Same as above except cytarabine (MiDAC) IV on days 1, 3, and 5.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Gemtuzumab Ozogamicin; Drug: Midostaurin

What is being measured

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

  1. Maximum-tolerated dose (MTD) of combining gemtuzumab ozogamicin with cytarabine, daunorubicin, and midostaurin

    The MTD will be estimated using isotonic regression. An incidence of dose limiting toxicity at each dose level will be summarized.

    Measured: 42 days after start of last induction (i.e. induction or re-induction)

Secondary outcomes (8)

  1. Incidence of 30-day treatment-related mortality

    Will be estimated with exact confidence intervals.

    Measured: Up to 30 days after receiving initial induction therapy

  2. Rate of complete composite remission (CCR)

    Complete composite remission is defined as meeting criteria for complete remission (CR), complete remission with incomplete blood count recovery (CRi), or complete remission with incomplete platelet recovery (CRp). Will be measured and reported with 95% exact confidence intervals.

    Measured: At end of consolidation treatment (up to 120 days)

  3. Objective response rate (ORR)

    ORR is defined as the sum of CR, CRi, Morphologic leukemia-free state (MLFS), and Partial remission (PR). Will be measured and reported with 95% exact confidence intervals.

    Measured: At end of consolidation treatment (up to 120 days)

  4. Event free survival

    EFS will be measured from start of on-study therapy (i.e., Day 1) to the date of primary refractory disease, relapse from CR or CRi, or death from any cause. Participants not known to have failed induction therapy, relapsed, or died at time of last follow-up will be censored on the date they were last examined (i.e., 2 years following completion of on-study therapy). The Kaplan-Meier method will be used. Mean and/or median survival and 95% confidence intervals will be reported, if available.

    Measured: From date of primary refractory disease, or relapse from complete response (CR) or complete remission with incomplete blood count recovery (CRi) , or death from any cause, assessed up to 24 months

  5. Duration of response

    For only participants that achieve CR or CRi, the DoR is measured from the date of first documented response (CR, CRi) until the date of relapse. Participants not known to have relapsed at time of last follow-up will be censored on the date they were last examined (i.e., 2 years following completion of on-study therapy). The Kaplan-Meier method will be used. Mean and/or median survival and 95% confidence intervals will be reported, if available.

    Measured: From date of first documented response (CR, CRi) to date of documented relapse, assessed up to 24 months

  6. Relapse-free survival

    For only participants that achieve CR or CRi, RFS will be measured from the date of first documented response (CR, CRi) to the date of relapse or death from any cause. Participants not known to have relapsed or died at time of last follow-up will be censored on the date they were last examined (i.e., 2 years following completion of on-study therapy). The Kaplan-Meier method will be used. Mean and/or median survival and 95% confidence intervals will be reported, if available.

    Measured: From date of first documented response (CR, CRi) to date of relapse or death from any cause, assessed up to 24 months

  7. Overall survival

    The Kaplan-Meier method will be used. Mean and/or median survival and 95% confidence intervals will be reported, if available.

    Measured: From start of treatment until death, assessed up to 24 months

  8. Incidence of adverse events and serious adverse events

    Will be tabulated and summarized by severity and major organ site according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 90 days after last dose of treatment

Timeline

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

  1. First posted3 Apr 2019
  2. Study start13 Mar 2019
  3. Primary completion8 Aug 2024
  4. Study completion23 Oct 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03900949
Sponsor's protocol ID
OSU-21190
Other IDs
NCI-2019-01726
Status last verified
May 2026
First submitted
1 Apr 2019
Last updated
15 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Jain J, Pugh K, Handa S, Dvorak-Kornaus KM, Zhao Q, Walter RB, Cook R, Saultz J, Swords R, Li J, Laszlo GS, Grieselhuber NR, Mims AS, Larkin KTM, Sahasrabudhe K, Blachly JS, Behbehani GK, Eisfeld AK, Long M, Srisuwananukorn A, Koenig KL, Borate U. Safety of gemtuzumab ozogamicin with cytarabine, daunorubicin, and midostaurin induction in FLT3-mutated AML. Blood Neoplasia. 2025 Oct 9;3(1):100171. doi: 10.1016/j.bneo.2025.100171. eCollection 2026 Feb.

    PubMed 41488889

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cytarabine and Daunorubicin Hydrochloride in people with Acute Myeloid Leukemia, run by Uma Borate at 2 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 11 inclusion and 12 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 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

Maximum-tolerated dose (MTD) of combining gemtuzumab ozogamicin with cytarabine, daunorubicin, and midostaurin (time frame: 42 days after start of last induction (i.e. induction or re-induction)). 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 NCT03900949, 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 15 May 2026.

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