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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 : June 5, 2020
Sponsor:
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief Summary:

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
Leukemia, Myeloid, Acute Drug: CPX-351 Drug: Quizartinib Phase 2

Detailed Description:
This is an open-label, two-part Phase II clinical trial in patients with relapsed or refractory FLT3-ITD mutation-positive acute myeloid leukemia (AML). The study is designed to assess the safety and tolerability as well as the efficacy of administering CPX-351 (cytarabine:daunorubicin liposome complex) with quizartinib. CPX-351 is a formulation of two drugs, cytarabine and daunorubicin, that is administered as the first part of treatment to get rid of as many leukemia cells in your bone marrow as possible. Quizartinib is an investigational drug made of a protein that inhibits FLT3 and will be given after CPX-351 has been given. The plan for administration is divided into three phases: induction, consolidation, and maintenance.

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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
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.
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.




Primary Outcome Measures :
  1. 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.

  2. 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/or 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)


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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/or 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

  7. 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

  8. 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

  9. 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.



Information from the National Library of Medicine

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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
Criteria

Inclusion Criteria:

  1. 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.
  2. 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
  3. 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.
  4. Patients must be able to swallow and retain oral medication.
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2 (Appendix A).
  6. 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:

  1. Acute promyelocytic leukemia (t[15;17])
  2. Female patients who are lactating or have a positive serum pregnancy test during the screening period.
  3. 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
  4. History of hypersensitivity to cytarabine, daunorubicin, or an FLT3 inhibitor
  5. Any patients with known significant impairment in gastrointestinal (GI) function or GI disease that my significantly alter the absorption of quizartinib.
  6. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  7. 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 on Day 8 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
  8. History of New York Heart Association Class 3 or 4 heart failure
  9. Prior anthracycline (or equivalent) cumulative exposure ≥368 mg/m2 daunorubicin (or equivalent)
  10. 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.
  11. Adequate pulmonary function (no supplemental O2 or diffusing capacity of the lungs for carbon monoxide [DLCO] <40%)
  12. Active acute or chronic GVHD requiring prednisone >10 mg or equivalent.

Information from the National Library of Medicine

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


Contacts
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Contact: Sarah Cannon 844-710-6157 CANN.InnovationsMedical@sarahcannon.com

Locations
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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         
Sponsors and Collaborators
SCRI Development Innovations, LLC
Investigators
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Study Chair: Michael Tees, MD, MPH Colorado Blood Cancer Institute
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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: June 5, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by SCRI Development Innovations, LLC:
FLT3
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms