← Back to Search

Gemtuzumab + Midostaurin for Acute Myeloid Leukemia

Phase 1

Recruiting

Led By Uma Borate, M.D.

Research Sponsored by OHSU Knight Cancer Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Must not have

Except for hydroxyurea, no other prior systemic anti-AML therapies may have been received prior to starting study therapy

Known active human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new combination of two drugs, gemtuzumab ozogamicin and midostaurin, to see if it is safe and tolerable in patients with newly diagnosed FLT3-mutated Acute Myeloid Leukemia (AML).

Who is the study for?

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.

What is being tested?

The 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.

What are the potential side effects?

Potential side effects may include reactions related to the immune system such as fever or chills during infusion, bleeding problems due to low blood cell counts, liver function changes, nausea or vomiting from chemotherapy drugs used in the treatment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

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

Select...

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

Select...

I do not have any severe heart conditions or recent heart attacks.

Select...

My cancer affects my blood or bone marrow.

Select...

I have been diagnosed with a specific type of leukemia.

Select...

I do not have any untreated infections.

Select...

I have a history of blood vessel blockage in my liver.

Select...

I cannot take medicine by mouth.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Secondary study objectives

Duration of response

Event free survival

Incidence of 30-day treatment-related mortality

+5 more

Other study objectives

CD33 expression

CD33 single nucleotide polymorphism (SNP)

Side effects data

From 2019 Phase 2 trial • 77 Patients • NCT01251575

Hypoxia

Febrile neutropenia

Acute kidney injury

Blood bilirubin increased

Diarrhea

Creatinine increased

Sepsis

Hypotension

Left ventricular systolic dysfunction

Bronchopulmonary hemorrhage

Chronic kidney disease

Thromboembolic event

Lung infection

Atrial fibrillation

Atrial flutter

Hemolysis

Hemolytic uremic syndrome

Ejection fraction decreased

Encephalitis infection

Gastric hemorrhage

Gastritis

Heart failure

Mucositis oral

Multi-organ failure

Myalgia

Pleural effusion

Respiratory failure

Small intestine infection

Syncope

Treatment related secondary malignancy

Typhlitis

Fever

Paroxysmal atrial tachycardia

Ascites

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (Fludarabine, Transplant, Immunosuppression)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cytarabine

2016

Completed Phase 3

~3330

Allogeneic Hematopoietic Stem Cell Transplantation

2012

Completed Phase 2

~1240