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

Refractory Acute Myeloid Leukemia Clinical Trial

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)

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. 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:

I. 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. ;

Related Conditions & MeSH terms

• FLT3 Gene Mutation Negative
• FLT3 Internal Tandem Duplication Positive
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndromes
• Preleukemia
• Recurrence
• Recurrent Acute Myeloid Leukemia
• Recurrent Chronic Myelomonocytic Leukemia
• Recurrent Myelodysplastic Syndrome
• Refractory Acute Myeloid Leukemia
• Refractory Chronic Myelomonocytic Leukemia
• Refractory Myelodysplastic Syndrome
• Syndrome

• NCT number: NCT01892371
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 12, 2013
• Completion date: February 7, 2023