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Chemotherapy Agent

Gilteritinib + Chemotherapy for Acute Myeloid Leukemia

Phase 1 & 2

Recruiting

Research Sponsored by Astellas Pharma Global Development, Inc.

Eligibility Criteria Checklist

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

Must have

For subject undergoing hematopoietic stem cell transplant (HSCT), at least 90 days must have elapsed since HSCT and subject must not have active graft-versus-host disease (GVHD).

Prior to screening, 90 days must have elapsed if the subject had a prior traumatic brain injury or has received craniospinal XRT.

Must not have

Subject has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The subject needs to be off pressors and have negative blood cultures for 48 hours.

Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A/P-glycoprotein (P-gp).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial will study gilteritinib in combination with fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG) to see if it is safe and effective in treating people with relapsed or refractory acute myeloid leukemia (AML).

Who is the study for?

This trial is for children, adolescents, and young adults aged ≥6 months to <21 years with FLT3/ITD positive relapsed or refractory AML. They must have recovered from prior treatments, not be pregnant or breastfeeding, agree to use contraception, and not have active CNS leukemia or significant heart disease.

What is being tested?

The study tests gilteritinib combined with chemotherapy (fludarabine, cytarabine, G-CSF) in two phases: Phase 1 finds the safest dose; Phase 2 checks how well it works. It measures remission rates after two cycles and monitors safety over a potential two-year treatment period.

What are the potential side effects?

Possible side effects include reactions related to the immune system's response to the drug combination (like inflammation), digestive issues due to chemotherapy agents used alongside gilteritinib, liver function changes, blood disorders such as anemia or clotting problems.

Eligibility Criteria

Inclusion Criteria

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

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It's been over 90 days since my stem cell transplant and I don't have active GVHD.

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It has been over 90 days since my last brain injury or craniospinal radiation.

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My blood or bone marrow has a FLT3 mutation.

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My liver enzymes, AST and ALT, are within normal limits.

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I have been diagnosed with a type of leukemia called AML with at least 5% cancer cells in my bone marrow.

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My AML did not respond to the first treatment or it has returned after initial success.

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I am receiving a specific chemotherapy at a low dose.

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My blood or bone marrow has the FLT3 mutation.

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I am between 6 months and 21 years old.

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My total bilirubin levels are within normal range for my age.

Exclusion Criteria

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

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I have an ongoing infection that hasn't improved with treatment, but I've been off pressors and had negative blood cultures for 48 hours.

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I need medication that strongly affects certain liver enzymes and proteins.

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I am allergic to gilteritinib, cytarabine, fludarabine, G-CSF, or their ingredients.

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I do not have serious heart problems.

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I am not planning to receive any cancer treatment outside of what this study involves.

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I have active leukemia in my brain or spinal cord.

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I tested negative for active hepatitis B but had it before, and my viral load is undetectable.

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My high blood pressure is not under control.

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I have cancer types other than acute myeloid leukemia.

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I have active hepatitis B, C, or another liver condition.

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I am known to have HIV.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Complete Remission (CR) rate after 2 cycles of therapy (phase 2)

Composite complete remission (CRc) rate after 2 cycles of therapy (phase 2)

Number of participants with dose limiting toxicity (DLT) (phase 1/dose escalation)

Secondary study objectives

Clinical Outcome Assessment of Taste

Duration of Event Free Survival (EFS)

Duration of Overall survival (OS)

+14 more

Side effects data

From 2023 Phase 3 trial • 356 Patients • NCT02997202

53%

Chronic graft versus host disease

38%

Acute graft versus host disease

28%

Neutrophil count decreased

25%

Diarrhoea

21%

Nausea

19%

Alanine aminotransferase increased

19%

Cough

19%

Blood creatine phosphokinase increased

18%

Platelet count decreased

17%

Anaemia

17%

Fatigue

16%

Aspartate aminotransferase increased

16%

Oedema peripheral

16%

Hypertension

13%

Vomiting

13%

Neutropenia

13%

Dizziness

12%

Upper respiratory tract infection

12%

Dry mouth

12%

White blood cell count decreased

12%

Thrombocytopenia

11%

Headache

11%

Dry eye

11%

Constipation

10%

Dyspnoea

10%

Viral upper respiratory tract infection

10%

Myalgia

10%

Blood creatinine increased

10%

Hypokalaemia

Pyrexia

Pneumonia

Back pain

Arthralgia

Dry skin

Blood alkaline phosphatase increased

Pain in extremity

Insomnia

Hypomagnesaemia

Hyperglycaemia

Muscle spasms

Pruritus

Rash maculo-papular

Oropharyngeal pain

Anxiety

Non-cardiac chest pain

Influenza

Rash

Abdominal pain

Decreased appetite

Hyperkalaemia

Peripheral sensory neuropathy

Blood lactate dehydrogenase increased

Neuropathy peripheral

Paraesthesia

Hypophosphataemia

Cytomegalovirus viraemia

Febrile neutropenia

Acute kidney injury

Respiratory syncytial virus infection

Lower respiratory tract infection

Viral sepsis

Rhinorrhoea

Escherichia sepsis

Urinary tract infection bacterial

Medication error

Sepsis

Device related infection

Squamous cell carcinoma of skin

Interstitial lung disease

Pneumothorax

Escherichia urinary tract infection

Eye infection

Colitis ulcerative

Lacunar stroke

Motor neurone disease

Renal impairment

Respiratory tract infection viral

Pericardial effusion

Pneumonia bacterial

Hepatic enzyme increased

Femur fracture

Graft versus host disease

Bronchopulmonary aspergillosis allergic

Bacteraemia

Accidental overdose

Fall

Stress fracture

COVID-19

Appendicitis

Viral haemorrhagic cystitis

Arthritis infective

Psychotic disorder

Phimosis

Electrocardiogram QT prolonged

Myelitis transverse

Somatic symptom disorder

Clostridial sepsis

Klebsiella sepsis

Atrial fibrillation

Cystitis haemorrhagic

Adrenal insufficiency

Graft versus host disease in lung

Epstein-Barr viraemia

Agranulocytosis

Death

Clostridium difficile colitis

Adenovirus infection

Neutropenic sepsis

Pharyngeal abscess

Skin cancer

Herpes zoster

Lower respiratory tract infection bacterial

Gastroenteritis norovirus

Gastrointestinal infection

Cytopenia

Encephalopathy

Cytomegalovirus colitis

Genital infection bacterial

Prinzmetal angina

Pneumonia fungal

Pneumocystis jirovecii pneumonia

Febrile bone marrow aplasia

Antithrombin III deficiency

Cystitis bacterial

Femoral neck fracture

Suicidal ideation

Respiratory failure

Hepatic function abnormal

Liver disorder

Oesophageal infection

Septic shock

Hyponatraemia

Syncope

Hypoxia

Deafness neurosensory

Duodenal ulcer haemorrhage

Ophthalmic herpes zoster

Cerebral haemorrhage

Embolism

Clostridium difficile infection

Cytomegalovirus enterocolitis

Enterobacter sepsis

Enterococcal sepsis

Lower respiratory tract infection fungal

Lower respiratory tract infection viral

Pseudomonal sepsis

Streptococcal bacteraemia

Viraemia

Bowen's disease

Gastroenteritis

Colitis

Hip fracture

Oropharyngeal squamous cell carcinoma

Deep vein thrombosis

Fluid overload

Muscular weakness

Post transplant lymphoproliferative disorder

Pseudomonas infection

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

Gilteritinib

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Dose ExpansionExperimental Treatment4 Interventions

Participants will be administered fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG) chemotherapy on days -1 to 5 and gilteritinib will be administered once per day on days 8 to 21 at the dose determined in dose escalation portion. Participants may receive prophylactic intrathecal cytarabine at the start of the cycle, as per institutional standards. A participant completing 2 cycles (cycle is defined as 28 days) will have the option to participate in long term treatment (LTT) with gilteritinib (for up to 2 years).

Group II: Dose Escalation - 6 months to less than 1 year of ageExperimental Treatment4 Interventions

Participants will be administered fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG) chemotherapy on days -1 to 5 and gilteritinib will be administered once per day on days 8 to 21 at the assigned dose. Participants may receive prophylactic intrathecal cytarabine at the start of the cycle, as per institutional standards. A participant completing 2 cycles (cycle is defined as 28 days) will have the option to participate in long term treatment (LTT) with gilteritinib (for up to 2 years).

Group III: Dose Escalation - 2 years to less than 21 years of ageExperimental Treatment4 Interventions

Participants will be administered fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG) chemotherapy on days -1 to 5 and gilteritinib will be administered once per day on days 8 to 21 at the assigned dose. Participants may receive prophylactic intrathecal cytarabine at the start of the cycle, as per institutional standards. A participant completing 2 cycles (cycle is defined as 28 days) will have the option to participate in long term treatment (LTT) with gilteritinib (for up to 2 years).

Group IV: Dose Escalation - 1 year to less than 2 years of ageExperimental Treatment4 Interventions

Participants will be administered fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG) chemotherapy on days -1 to 5 and gilteritinib will be administered once per day on days 8 to 21 at the assigned dose. Participants may receive prophylactic intrathecal cytarabine at the start of the cycle, as per institutional standards. A participant completing 2 cycles (cycle is defined as 28 days) will have the option to participate in long term treatment (LTT) with gilteritinib (for up to 2 years).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

gilteritinib

2016

Completed Phase 3

~430

cytarabine

1997

Completed Phase 3

~10270