Gemtuzumab + Midostaurin for Acute Myeloid Leukemia

Recruiting in Palo Alto (17 mi)

+2 other locations

Dr. Uma Borate - Hematology - Columbus, OH

Overseen byUma Borate, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: OHSU Knight Cancer Institute

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for adults with newly diagnosed FLT-3 mutated Acute Myeloid Leukemia (AML) who can sign consent, have an ECOG status of ≤2, and CD33 positive AML. They must not have had previous AML treatments, no active HIV or hepatitis B/C, and agree to contraception use. Those with severe heart issues, uncontrolled infections or certain allergies are excluded.

Inclusion Criteria

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 3 months following the last dose of study treatment. They must also refrain from sperm donation from the screening visit until 90 days following the last dose of study treatment

I can take care of myself but might not be able to do heavy physical work.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

I have only used hydroxyurea for my AML, no other treatments.

I do not have active HIV, hepatitis B, or hepatitis C.

My AML has spread to my brain or spinal cord, confirmed by a spinal tap.

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Treatment Details

Interventions

Cytarabine (Chemotherapy)
Daunorubicin Hydrochloride (Anti-tumor antibiotic)
Gemtuzumab Ozogamicin (Monoclonal Antibodies)
Midostaurin (Protein Kinase Inhibitor)

Trial OverviewThe study tests a combination of gemtuzumab ozogamicin (GO) and midostaurin with standard cytarabine and daunorubicin chemotherapy in patients with new FLT-3 mutated AML. It aims to find out if this novel approach is safe and how well patients tolerate it.

Participant Groups

1Treatment groups

Experimental Treatment

Group I: Treatment (gemtuzumab ozogamicin, cytarabine, daunorubicin)Experimental Treatment5 Interventions

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.

Cytarabine is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Cytosar-U for: