Quizartinib, Decitabine, and Venetoclax in Treating Participants With Untreated or Relapsed Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome
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|ClinicalTrials.gov Identifier: NCT03661307|
Recruitment Status : Recruiting
First Posted : September 7, 2018
Last Update Posted : October 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Blasts More Than 10 Percent of Bone Marrow Nucleated Cells Blasts More Than 10 Percent of Peripheral Blood White Cells High Risk Myelodysplastic Syndrome Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Recurrent Myelodysplastic Syndrome Refractory Acute Myeloid Leukemia TP53 Gene Deletion TP53 Gene Mutation||Drug: Decitabine Drug: Quizartinib Drug: Venetoclax||Phase 1 Phase 2|
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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.
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.
II. To investigate correlations of response to this combination with a pre-therapy, on-therapy, and progression 81-gene panel of gene mutations in AML.
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 I 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||52 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||October 31, 2018|
|Estimated Primary Completion Date :||January 1, 2021|
|Estimated Study Completion Date :||January 1, 2022|
Experimental: Treatment (decitabine, quizartinib, venetoclax)
Patients receive decitabine IV over 1 hour on days 1-10, quizartinib 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.
- Maximum tolerated dose of the combination drugs (Phase I) [ Time Frame: Up to 28 days ]
- Incidence of adverse events (Phase II) [ Time Frame: Within 3 months ]
- 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) (Phase II) [ Time Frame: Within 3 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03661307
|Contact: Musa Yilmazfirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Musa Yilmaz 713-745-9945|
|Principal Investigator: Musa Yilmaz|
|Principal Investigator:||Musa Yilmaz||M.D. Anderson Cancer Center|