A Study of CPX-351 (Vyxeos™) With Quizartinib for the Treatment of FLT3-ITD Mutation-Positive Acute Myeloid Leukemia

NCT04209725 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: SCRI AML 48
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 5

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.

Conditions

Leukemia, Myeloid, Acute

Keywords

FLT3

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Treatment Related Adverse Events After Taking CPX-351 and Quizartinib

  Counting the number of patients with treatment related adverse events as a measure of safety and tolerability.

  Collected during treatment and for 30 days after last dose, approximately 35 total days for the 1 patient treated.

• Number of Patients With an Overall Response Taking CPX-351 and Quizartinib

  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)

  from cycle 1 day 1 (each cycle is 28 days) until disease progression for up to 2 years post treatment

Secondary Outcomes (12)

• Median Time to Platelet Count Recovery

  from cycle 1 Day 1 (each cycle is 28 days) for up to 24 months

• Median Time to Absolute Neutrophil Count (ANC) Recovery

  from Cycle 1 Day 1 (each cycle is 28 days) for up to 24 months

• Number of Patients Proceeding to an Allogeneic Hematopoietic Cell Transplantation (alloHCT)

  up to 60 days after consolidation therapy

• Median Time to Disease Progression

  from diagnosis of relapse or refractory AML until disease progression for up to 2 years post treatment

• Event-free Survival Time

  from day 1 for up to 4 years

Study Arms (1)

CPX-351 and Quizartinib treatment

EXPERIMENTAL

Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance.

Drug: CPX-351; Drug: Quizartinib

Interventions

CPX-351 DRUG

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.

Also known as: Vyxeos

CPX-351 and Quizartinib treatment

Quizartinib DRUG

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.

CPX-351 and Quizartinib treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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)

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead

Study Sites (5)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

HCA Midwest

Kansas City, Missouri, 64132, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

St. David's South Austin Medical Center

Austin, Texas, 78704, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

CPX-351; quizartinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Sarah Cannon Development Innovations, LLC
• Organization: Sarah Cannon Development Innovations, LLC

CANN.InnovationsMedical@sarahcannon.com

844-710-6157

Study Officials

• Michael Tees, MD, MPH

  Colorado Blood Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: December 24, 2019
• Study Start: June 3, 2020
• Primary Completion: April 20, 2021
• Study Completion: April 20, 2021
• Last Updated: December 5, 2023
• Results First Posted: June 3, 2022

Record last verified: 2022-05

Locations

US (5)