A Study of CPX-351 (Vyxeos™) With Quizartinib for the Treatment of FLT3-ITD Mutation-Positive Acute Myeloid Leukemia
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ClinicalTrials.gov Identifier: NCT04209725 |
Recruitment Status :
Recruiting
First Posted : December 24, 2019
Last Update Posted : October 8, 2020
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This is a research study to be done at multiple sites in participants with advanced acute myeloid leukemia (AML) that have a mutation in Fms-like tyrosine kinase-3 internal tandem duplications (FLT3-ITD). This study is to learn more about an investigational drug, quizartinib, being tested with the anti-cancer medicine CPX-351 (also called Vyxeos™), which is approved and widely used to treat AML.
The purpose of this study is to assess the safety, tolerability and survival of patients receiving the combination of CPX-351 and quizartinib.
Condition or disease | Intervention/treatment | Phase |
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Leukemia, Myeloid, Acute | Drug: CPX-351 Drug: Quizartinib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 34 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase II Study Assessing CPX-351 (Vyxeos™) With Quizartinib for the Treatment of Relapsed or Refractory FLT3-ITD Mutation-Positive AML |
Actual Study Start Date : | June 3, 2020 |
Estimated Primary Completion Date : | January 2024 |
Estimated Study Completion Date : | January 2024 |

Arm | Intervention/treatment |
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Experimental: CPX-351 and Quizartinib treatment
Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance.
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Drug: CPX-351
To be given during the induction and consildation phase and will consist of 44 mg/m^2 daunorubicin with 100 mg/m^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase.
Other Name: Vyxeos Drug: Quizartinib To be given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase. |
- Number of patients with treatment related adverse events after taking CPX-351 and quizartinib [ Time Frame: from the start of treatment for approximately 24 months ]Counting the incidence of patients with treatment related adverse events as a measure of safety and tolerability.
- Determine the number of patients with an overall response taking CPX-351 and quizartinib [ Time Frame: from cycle 1 day 1 (each cycle is 28 days) until disease progression for up to 2 years post treatment ]Overall response is defined by the International Working Group response criteria (Cheson et al 2003) as having a complete remission (CR) - a complete morphologic response with complete blood count recovery absolute neutrophil count ≥1000/μL and platelet count ≥100,000/μL) or a complete morphologic response with an incomplete blood count recovery (CRi) - absolute neutrophil count <1000/μL and/or platelet count <100,000/μL)
- Median time to platelet count recovery [ Time Frame: from cycle 1 Day 1 (each cycle is 28 days) for up to 24 months ]Time to platelet recovery is defined as the time to when the peripheral blood platelet count is >50, 000/ μL
- Median time to absolute neutrophil count (ANC) recovery [ Time Frame: from Cycle 1 Day 1 (each cycle is 28 days) for up to 24 months ]Time to neutrophil recovery is defined as the time to when the peripheral blood ANC is ≥500/μL
- Number of patients proceeding to an allogeneic hematopoietic cell transplantation (alloHCT) [ Time Frame: up to 60 days after consolidation therapy ]Patients receiving allogeneic hematopoietic cell transplantation (alloHCT) following treatment in induction and consolidation therapies.
- Median time to disease progression [ Time Frame: from cycle 1 day 1 (each cycle is 28 days) until disease progression for up to 2 years post treatment ]Time to disease progression, confirmed by bone marrow biopsy.
- Determine event-free survival time [ Time Frame: from day 1 for up to 4 years ]Defined as the number of days until date of evidence of progressive disease by bone marrow biopsy/aspirate or death.
- Determine the number of patients who develop late responses [ Time Frame: up to 4 years ]Late responses as defined by the International Working Group response criteria (Cheson et al 2003) as having a complete remission (CR) - a complete morphologic response with complete blood count recovery absolute neutrophil count ≥1000/μL and platelet count ≥100,000/μL) or a complete morphologic response with an incomplete blood count recovery (CRi) - absolute neutrophil count <1000/μL and/or platelet count <100,000/μL
- Define the number of patients who can receive consolidation and maintenance therapy [ Time Frame: approximately 3 months ]Patients who proceed through induction to next stages of consolidation and maintenance
- Define the treatment-related mortality rate [ Time Frame: after end of treatment every 6 months for up to 2 years ]As determined by the number of treatment related deaths on study
- Determine the percentage of patients who achieve a PR or molecular complete remission [ Time Frame: from cycle 1 day 1 (each cycle is 28 days) until disease progression for up to 2 years post treatment ]A PR is defined as persistent disease by morphology but with a >50% reduction in the blast count/cellularity ratio compared to the most recent BM biopsy prior to treatment. A molecular complete remission is defined as no evidence of disease by bone marrow biopsy/aspirate by morphology, immunohistochemistry, or flow cytometry, and FLT3 mutation by MRD analysis.

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Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Written informed consent form (ICF), according to local guidelines, signed by the patient or by a legal guardian prior to the performance of any study-related screening procedures.
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Patients with the following types of AML with >5% blasts:
- Relapsed FLT3-ITD mutation-positive AML, diagnosed by bone marrow (BM) biopsy with FLT3 mutation by polymerase chain reaction (PCR)
- Refractory FLT3-ITD mutation-positive AML, diagnosed by BM biopsy with FLT3 mutation by PCR
- Relapsed or refractory FLT3-ITD mutation-positive AML after HCT, diagnosed by BM biopsy with FLT3 mutation by PCR
- Relapsed or refractory AML with de novo FLT3-ITD mutation, diagnosed by BM biopsy with FLT3 mutation by PCR
- Relapsed or refractory AML after HCT with de novo FLT3-ITD mutation, diagnosed by BM biopsy with FLT3 mutation by PCR
- First-line therapy must have contained a standard induction chemotherapy (e.g. 7+3, FLAG-IDA, FLAG, CLAG, MEC, hypomethylating agent with venetoclax) with or without receiving a prior FLT3 inhibitor (e.g. midostaurin) or multi-tyrosine kinase inhibitor (e.g. sorafenib). All patients who relapsed after an alloHCT are included, except patients with active graft-versus-host disease (GVHD) requiring >10 mg prednisone.
- Patients must be able to swallow and retain oral medication.
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2 (Appendix A).
- Adequate renal and hepatic parameters (aspartate aminotransferase [AST], alanine aminotransferase [ALT] ≤2.5 institutional upper limit of normal [ULN]; total bilirubin ≤2.0 institutional ULN; serum creatinine [Cr] ≤2.0). In patients with suspected liver infiltration, ALT can be ≤5 institutional ULN.
Exclusion Criteria:
- Acute promyelocytic leukemia (t[15;17])
- Female patients who are lactating or have a positive serum pregnancy test during the screening period. Female patients of childbearing potential who are not willing to employ highly effective birth control (as defined in Appendix C of protocol) from screening to 6 months following the last dose of CPX-351 and/or quizartinib.
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Evidence of active and uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of active infection progression are present. This is assessed by the site clinicians, including an infectious disease consulting physician, if requested by the Principal Investigator (PI), regarding adequacy of therapy. These infections include, but are not limited to:
- Known human immunodeficiency virus (HIV) infection
- Active hepatitis B or C infection with rising transaminase values
- Active tuberculosis infection
- History of hypersensitivity to cytarabine, daunorubicin, or an FLT3 inhibitor
- Any patients with known significant impairment in gastrointestinal (GI) function or GI disease that my significantly alter the absorption of quizartinib.
- Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
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Uncontrolled or significant cardiovascular disease, including any of the following:
- Bradycardia of less than 50 beats per minute, unless the patient has a pacemaker
- QTcF interval using Fridericia's correction factor (QTcF) interval prolongation, defined as >450msec at screening and prior to first administration of quizartinib
- Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome)
- Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg
- History of clinically relevant ventricular arrhythmias (i.e., ventricular tachycardia, ventricular fibrillation or Torsades de pointes)
- History of second or third degree heart block without a pacemaker
- Right bundle branch and left anterior hemiblock (bifascicular block), complete left bundle branch block
- Ejection fraction <50% by transthoracic echocardiogram (TTE) or multigated acquisition (MUGA) scan
- History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to Screening
- History of New York Heart Association Class 3 or 4 heart failure
- Prior anthracycline (or equivalent) cumulative exposure ≥368 mg/m2 daunorubicin (or equivalent)
- Any serious underlying medical condition that, in the opinion of the Investigator or Medical Monitor, would impair the ability to receive or tolerate the planned treatment.
- Patients with inadequate adequate pulmonary function will be excluded. Inadequate pulmonary function is defined as requiring supplemental O2, or diffusing capacity of the lungs for carbon monoxide [DLCO] <40%.
- Active acute or chronic GVHD requiring prednisone >10 mg or equivalent.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04209725
Contact: Sarah Cannon | 844-710-6157 | CANN.InnovationsMedical@sarahcannon.com |
United States, Colorado | |
Colorado Blood Cancer Institute | Recruiting |
Denver, Colorado, United States, 80218 | |
Principal Investigator: Marcello Rotta, MD | |
United States, Missouri | |
HCA Midwest | Recruiting |
Kansas City, Missouri, United States, 64132 | |
Principal Investigator: Suman Kambhampati, MD | |
United States, Tennessee | |
Tennessee Oncology | Recruiting |
Nashville, Tennessee, United States, 37203 | |
Principal Investigator: William Donnellan, MD | |
United States, Texas | |
St. David's South Austin Medical Center | Recruiting |
Austin, Texas, United States, 78704 | |
Principal Investigator: Aravind Ramakrishnan, MD | |
Texas Transplant Institute | Recruiting |
San Antonio, Texas, United States, 78229 | |
Principal Investigator: Cesar Freytes, MD |
Study Chair: | Michael Tees, MD, MPH | Colorado Blood Cancer Institute |
Responsible Party: | SCRI Development Innovations, LLC |
ClinicalTrials.gov Identifier: | NCT04209725 |
Other Study ID Numbers: |
SCRI AML 48 |
First Posted: | December 24, 2019 Key Record Dates |
Last Update Posted: | October 8, 2020 |
Last Verified: | October 2020 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
FLT3 |
Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms by Histologic Type Neoplasms |