FLT3 Gene Mutation NegativePhase 1/2NCT01892371

Quizartinib With Azacitidine or Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

A Phase 1/2 study testing Azacitidine, Cytarabine and Quizartinib in people with FLT3 Gene Mutation Negative and FLT3 Internal Tandem Duplication Positive, run by M.D. Anderson Cancer Center at 1 site 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

Who is it for?: Ages 18 years and older
Conditions the study is for: FLT3 Gene Mutation Negative, FLT3 Internal Tandem Duplication Positive, Recurrent Acute Myeloid Leukemia
What is being tested?: Azacitidine, Cytarabine and Quizartinib
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 73 participants
Where: 1 siteUnited States
Study dates: 12 Nov 2013to 7 Feb 2023
Phase: Phase 1/2

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

PHASE I
Refractory or relapsed disease defined as follows: patients with MDS or chronic myelomonocytic leukemia (CMML) should have failed prior therapy (e.g., with a hypomethylating agent, clofarabine, and/or with lenalidomide); patients with AML should have failed any prior induction therapy or have relapsed after prior therapy; patients (any age) with MDS or CMML who received therapy with a hypomethylating agent and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML. The World Health Organization (WHO) classification will be used for AML; patients with any of the eligible diagnoses who have received no prior therapy are eligible if not candidates to receive standard intensive therapy (i.e., high-dose cytarabine-based chemotherapy).
Patients are eligible regardless of their FLT3 mutation status.
PHASE II
COHORT 2A: Patients with MDS, CMML or AML who are either: age 60 years or older and newly diagnosed, previously untreated. Prior therapy with hydroxyurea or single agent ara-C for the purpose of control of white blood cells (WBC) is acceptable.; age 18 years or older and with refractory or relapse disease who have received no more than one prior treatment regimen and will be receiving first salvage. For this purpose, a second induction cycle with the same drugs used during the first cycle, consolidation chemotherapy or stem cell transplant in complete remission (CR) (or complete response with incomplete platelet recovery [CRp] or complete response with incomplete bone marrow recovery [CRi]) will be considered part of the prior regimen. Prior therapy for MDS (or other malignancies) is not considered a prior regimen for AML in patients who progress from MDS (or other malignancies).
COHORT 2A: Patients (any age) with MDS or CMML who received therapy with a hypomethylating agent and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML. The WHO classification will be used for AML.

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COHORT 2A: Patients must have evidence of FLT3 ITD in their most recent assessment.
COHORT 2B: Patients with MDS, CMML or AML who are either: Age 60 years or older and newly diagnosed, previously untreated. Prior therapy with hydroxyurea or single agent ara-C for the purpose of control of WBC is acceptable or age 18 years or older and with refractory or relapse disease who have received no more than two prior treatment regimens and will be receiving second salvage, or who have received a prior SCT and will be receiving their first salvage. For this purposes, a second induction cycle with the same drugs used during the first cycle, consolidation chemotherapy or stem cell transplant in CR (or CRp or CRi) will be considered part of the prior regimen. Prior therapy for MDS (or other malignancies) is not considered a prior regimen for AML in patients who progress from MDS (or other malignancies)
COHORT 2B: Patients (any age) with MDS or CMML who received therapy with a hypomethylating agent and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML. The WHO classification will be used for AML
COHORT 2B: Patients must have no evidence of FLT3 mutations in their most recent assessment
PHASE I AND II
Eastern Cooperative Oncology Group (ECOG) performance status =< 2.
Bilirubin =< 2 x upper limit of normal (ULN).
Alanine aminotransferase (ALT) =< 2.5 x ULN.
For patients with suspected liver infiltration from leukemia ALT should be =< 5 ULN.
Creatinine =< 2 x ULN.
Serum potassium, magnesium, and calcium (normalized for albumin) levels should be at least within institutional normal limits.
Patients must provide written informed consent.
Patients must have been off chemotherapy for 2 weeks prior to entering this study, unless there is evidence of rapidly progressive disease, and must have recovered from the toxic effects of that therapy to at least grade 1. Use of hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy. The additional days of hydrea after 28 is permitted as clinically indicated, on case by case basis after discussion with the principal investigator (PI). Other agents given transiently with the intention to control rapid proliferation such as 1-2 doses of single agent ara-C or few doses of sorafenib are also allowed.
Women of childbearing potential must practice contraception. Women considered not of childbearing potential include any of the following: no menses for at least 2 years or menses within 2 years but amenorrheic for at least 2 months and luteinizing hormone (LH) and follicular stimulating hormone (FSH) values within normal range (according to definition of postmenopausal for laboratory used) or bilateral oophorectomy or radiation castration and amenorrheic for at least 3 months. Females of childbearing potential should practice effective methods of contraception. Effective methods of contraception include barrier methods (e.g., condoms, diaphragm), spermicidal jelly or foam, oral, depo provera, or injectable contraceptives, intrauterine devices, tubal ligation, and abstinence. Male patients with female partners who are of childbearing potential should also practice contraception.
Negative urine or serum pregnancy test.

Who cannot join

Patients with known allergy or hypersensitivity to quizartinib, mannitol, AZA, cytarabine or any of their components.
Serum potassium < 3.5 mEq/L despite supplementation, or > 5.5 mEq/L.
Serum magnesium above or below the institutional normal limit despite adequate management.
Serum calcium (corrected for albumin levels) above or below institutional normal limit despite adequate management.
Patients with known significant impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of quizartinib.
Patients with any other known disease concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, cardiovascular disease including congestive heart failure, myocardial infarction within 6 months and poorly controlled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study. Patients with current active malignancies or any remission for < 6 months, except patients with carcinoma in situ or with non-melanoma skin cancer who may have active disease or be in remission for less than 6 months.

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Patients with a known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis.
Patients who have had any major surgical procedure within 14 days of day 1.
Patients with known malignant disease of the central nervous system.
Impaired cardiac function including any of the following: screening electrocardiography (ECG) with a corrected QT (QTc) > 450 msec. The QTc interval will be calculated by Fridericia's correction factor (QTcF) at screening and on day 5 prior to the first dose of AC220. The QTcF will be derived from the average QTcF in triplicate; if QTcF > 450 msec on day 5, AC220 will not be given; patients with congenital long QT syndrome; history or presence of sustained ventricular tachycardia requiring medical intervention; any history of clinically significant ventricular fibrillation or torsades de pointes; Known history of second or third degree heart block (may be eligible if the patient currently has a pacemaker); sustained heart rate of < 50/minute on pre-entry ECG; right bundle branch block + left anterior hemiblock (bifascicular block); patients with myocardial infarction or unstable angina within 6 months prior to starting study drug; congestive heart failure (CHF) New York (NY) Heart Association class III or IV. Atrial fibrillation documented within 2 weeks prior to first dose of study drug; patients who require treatment with concomitant drugs that prolong QT/QTc interval or strong CYP3A4 inhibitors or inducers with the exception of antibiotics, antifungals, and antivirals that are used as standard of care to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject.
Known family history of congenital long QT syndrome.

Trial locations and contacts

1 site in 1 country.

United States1 site

M D Anderson Cancer Center
Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I/II Study of the Combination of Quizartinib (AC220) With 5-Azacytidine or Low-Dose Cytarabine for the Treatment of Patients With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

This phase I/II trial studies the side effects and best dose of quizartinib when given in combination with azacitidine or cytarabine in treating patients with acute myeloid leukemia or myelodysplastic syndrome that have come back (relapsed) or are not responding to treatment (refractory). Quizartinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine and cytarabine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving quizartinib with azacitidine or cytarabine may work better in patients with acute myeloid leukemia or myelodysplastic syndrome.

Read the detailed description

PRIMARY OBJECTIVES:

To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of the combination of quizartinib (AC220) with either azacitidine (5-azacitidine [AZA]) or low-dose cytarabine (LDAC) in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). (Phase I) II. To determine the clinical activity of the combination of quizartinib with either AZA or LDAC in patients with AML or MDS. (Phase II)

SECONDARY OBJECTIVES:

To determine the clinical activity of the combination of quizartinib with either AZA or LDAC in patients with AML or MDS. (Phase I) II. To determine the safety of the combination of quizartinib with either AZA or LDAC in patients with AML or MDS. (Phase II) III. To determine the induction of hypomethylation, deoxyribonucleic acid (DNA) damage and FLT3 signaling during therapy with this combination and its correlation with response. (Phase I and II) IV. To determine the effect of this combination therapy on plasma levels of FLT3-ligand. (Phase I and II) V. To determine the pharmacodynamics of this combination therapy in patients with AML or high-risk MDS. (Phase I and II)

OUTLINE: This is a phase I, dose-escalation study of quizartinib followed by a phase II study. Participants are assigned to 1 of 2 arms.

ARM I: Patients receive quizartinib orally (PO) once daily (QD) on days 5-28 of cycle 1 and on days 1-28 of subsequent cycles and azacitidine subcutaneously (SC) or intravenously (IV) over 10-40 minutes on days 1-7. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive quizartinib PO QD on days 5-28 of cycle 1 and on days 1-28 of subsequent cycles and cytarabine SC twice daily (BID) on days 1-10. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6-12 months.

Conditions: FLT3 Gene Mutation Negative, FLT3 Internal Tandem Duplication Positive, Recurrent Acute Myeloid Leukemia, Recurrent Chronic Myelomonocytic Leukemia, Recurrent Myelodysplastic Syndrome, Refractory Acute Myeloid Leukemia
Being tested: Azacitidine, Cytarabine, Quizartinib
Medical subject headings: Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes

What participants receive

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

AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC
Given SC or IV
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 SC
QuizartinibDrug
Also called AC-220, AC010220, AC220
Given PO

Study groups in NCT01892371
Study group	Role	What they receive
Phase 1 Arm I (quizartinib, azacitidine)	Experimental	Patients receive quizartinib PO QD on days 5-28 of cycle 1 and on days 1-28 of subsequent cycles and azacitidine SC or IV over 10-40 minutes on days 1-7. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Azacitidine; Drug: Quizartinib
Phase 1 Arm II (quizartinib, cytarabine)	Experimental	Patients receive quizartinib PO QD on days 5-28 of cycle 1 and on days 1-28 of subsequent cycles and cytarabine SC BID on days 1-10. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Cytarabine; Drug: Quizartinib
Phase 2 Arm I (quizartinib, azacitidine)	Experimental	Patients receive quizartinib PO QD on days 5-28 of cycle 1 and on days 1-28 of subsequent cycles and azacitidine SC or IV over 10-40 minutes on days 1-7. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Azacitidine; Drug: Quizartinib
Phase 2 Arm II (quizartinib, cytarabine)	Experimental	Patients receive quizartinib PO QD on days 5-28 of cycle 1 and on days 1-28 of subsequent cycles and cytarabine SC BID on days 1-10. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Cytarabine

What is being measured

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

Maximum Tolerated Dose of Quizartinib (Phase I)
Measured: At 28 days
Participants With a Response
(complete remission [CR]+complete response with incomplete bone marrow recovery [CRI]+partial remission [PR]+ hematologic improvement [HI]). Complete Rmission (CR) is bone marrow blasts of </= 5%, platelets >/= 100 and Absolute Neutrophil Count of >/= 1000. complete response with incomplete bone marrow recovery [CRI] is is bone marrow blasts of </= 5%, platelets >/= 100 or Absolute Neutrophil Count of >/= 1000. Hematologic improvement [HI]) is Bone Marrow Blasts </= 5%. Partial remission [PR] is bone marrow blasts of </= 5% with > 50% reduction, platelets >/= 100 and Absolute Neutrophil Count of >/= 1000.
Measured: At 56 days

Timeline

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

12 Nov 20137 Feb 2023

First posted4 Jul 2013 (estimated)
Study start12 Nov 2013
Primary completion7 Feb 2023
Study completion7 Feb 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for FLT3 Gene Mutation NegativeStudies of the same condition, open and under way.
More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 73 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01892371
Sponsor's protocol ID: 2012-1047
Other IDs: NCI-2018-01813, 2012-1047
Status last verified: Sep 2026
First submitted: 1 Jul 2013
Last updated: 23 Oct 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No