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

NCT03900949 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-21190NCI-2019-01726
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief 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). 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.

Conditions

Acute Myeloid Leukemia

Keywords

FLT; FLT-3; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (8)

• Incidence of 30-day treatment-related mortality

  Up to 30 days after receiving initial induction therapy

• Rate of complete composite remission (CCR)

  At end of consolidation treatment (up to 120 days)

• Objective response rate (ORR)

  At end of consolidation treatment (up to 120 days)

• Event free survival

  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

• Duration of response

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

Other Outcomes (2)

• CD33 expression

  Up to 24 months

• CD33 single nucleotide polymorphism (SNP)

  Up to 24 months

Study Arms (1)

Treatment (gemtuzumab ozogamicin, cytarabine, daunorubicin)

EXPERIMENTAL

INDUCTION 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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Gemtuzumab Ozogamicin; Drug: Midostaurin

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic SCT

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (gemtuzumab ozogamicin, cytarabine, daunorubicin)

Cytarabine DRUG

Given IV

Also known as: .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, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (gemtuzumab ozogamicin, cytarabine, daunorubicin)

Daunorubicin Hydrochloride DRUG

Given IV

Also known as: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin Hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, Rubilem

Treatment (gemtuzumab ozogamicin, cytarabine, daunorubicin)

Gemtuzumab Ozogamicin DRUG

Given IV

Also known as: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, gemtuzumab, hP67.6-Calicheamicin, Mylotarg, WAY-CMA-676

Treatment (gemtuzumab ozogamicin, cytarabine, daunorubicin)

Midostaurin DRUG

Given PO

Also known as: CGP 41251, CGP41251, N-Benzoyl-Staurosporine, N-Benzoylstaurosporine, PKC-412, PKC412, Rydapt

Treatment (gemtuzumab ozogamicin, cytarabine, daunorubicin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Uma Borate: lead

Study Sites (2)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University Knight Cancer Institute - Northwest Portland

Portland, Oregon, 97210, United States

Location

Related Publications (1)

• 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.

  PMID: 41488889 DERIVED

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Stem Cell Transplantation; Cytarabine; Daunorubicin; Gemtuzumab; midostaurin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Calicheamicins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Uma Borate, M.D.

  The Ohio State Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 1, 2019
• First Posted: April 3, 2019
• Study Start: March 13, 2019
• Primary Completion: August 8, 2024
• Study Completion: October 23, 2025
• Last Updated: October 28, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)