Quizartinib, Decitabine, and Venetoclax in Treating Participants With Untreated or Relapsed Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Acute Myeloid Leukemia Clinical Trial

Official title: A Phase I/II Study of Quizartinib in Combination With Decitabine and Venetoclax for the Treatment of Patients With Acute Myeloid Leukemia (AML)

Status Recruiting

Clinical Trial Summary

This phase I/II trial studies how well quizartinib, decitabine, and venetoclax work in treating participants with acute myeloid leukemia or high risk myelodysplastic syndrome that is untreated or has come back (relapsed). Quizartinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine and venetoclax, 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 and decitabine may work better at treating acute myeloid leukemia and myelodysplastic syndrome.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the overall response rate (ORR) including CR (complete remission) + CRp (complete remission with incomplete platelet recovery) + CRi (complete remission with incomplete count recovery) + partial remission (PR) within 3 months of treatment initiation of quizartinib and decitabine + venetoclax combination in patients with newly diagnosed or relapsed acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS) (> 10% blasts).

II. To determine the safety and maximum tolerable dose (MTD) of this combination.

SECONDARY OBJECTIVES:

I. To determine CR and CR+CRh rates within 3 months of treatment initiation of quizartinib and decitabine + venetoclax combination in patients with newly diagnosed or relapsed AML or high risk MDS (> 10% blast).

II. To determine the duration of response (DOR), event-free survival (EFS), overall survival (OS), MRD status at response and best MRD response attained by flow-cytometry (all patients) and by FLT3-PCR (if applicable) or variant allele frequency monitoring (if applicable) and number of patients bridged to hematopoietic stem cell transplant (HSCT) and median duration to HSCT from the initiation of the combination.

III. To investigate correlations of response to this combination with a pre-therapy, on-therapy, and progression 81-gene panel of gene mutations in AML.

EXPLORATORY OBJECTIVES:

I. To investigate possible relationships between response and non-response to the combination with pretherapy, on-therapy, and progression gene expression signatures.

II. To investigate the characterization of genetic heterogeneity in tumor cell populations, by performing targeted single-cell sequencing on longitudinally collected AML tumor populations from patients using a novel microfluidic approach that barcodes amplified genomic DNA from thousands of individual leukemia cells confined to droplets (single cell sequencing).

III. To identify individual treatment-resistant cell populations and how their signaling state in disease relates to clinical outcomes we will perform CyTOF (mass cytometry) on patients' bone marrow samples and peripheral blood at diagnosis, remission and relapse.

IV. To store and/or analyze surplus blood or tissue including bone marrow, if available, for potential future exploratory research into factors that may influence development of AML and/or response to the combination (where response is defined broadly to include efficacy, tolerability or safety).

OUTLINE: This is a phase I, dose escalation study followed by a phase II study.

Patients receive decitabine intravenously (IV) over 1 hour on days 1-10, quizartinib orally (PO) every day beginning on day 1 of cycle 1, and venetoclax PO on days 1-14 (days 1-21 if persistent leukemia). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months for up to 5 years. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Recurrence
• Recurrent Acute Myeloid Leukemia
• Recurrent Myelodysplastic Syndrome
• Refractory Acute Myeloid Leukemia
• Syndrome

• NCT number: NCT03661307
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Contact: Musa Yilmaz
• Phone: 713-745-9945
• Email: myilmaz@mdanderson.org
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 31, 2018
• Completion date: January 1, 2026