Liposomal Cytarabine and Daunorubicin (CPX-351) and Quizartinib for the Treatment of Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome

What this study involves

The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.

Study type

Interventional

Phase

Phase 1 / Phase 2

Age range

18 years - Not specified

Sex eligible

All sexes

Healthy volunteers

Not accepted

Participants

52 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

This phase I/II trial studies the side effects and best dose of CPX-351 in combination with quizartinib for the treatment of acute myeloid leukemia and high risk myelodysplastic syndrome. CPX-351, composed of chemotherapy drugs daunorubicin and cytarabine, works 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. Quizartinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The goal of this study is to learn if the combination of CPX-351 and quizartinib can help to control acute myeloid leukemia and myelodysplastic syndrome.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

Inclusion Criteria:

• Diagnosis of 1) AML (World Health Organization \[WHO\] classification definition of \>= 20% blasts, excluding acute promyelocytic leukemia \[APL\]), or 2) high risk MDS (\> 10% bone marrow blasts)
• For frontline cohort: Patients aged \>= 60 years old
• For relapsed or refractory cohort: Patients aged \>= 18 years old
• For frontline cohort: Patients must be chemonaive, i.e., not have received any chemotherapy (except hydrea or 1-2 doses of ara-C for transient control of hyperleukocytosis) for AML or MDS. They may have received transfusions, hematopoietic growth factors or vitamins for an antecedent hematological disorder (AHD) or for AML. Temporary prior measures such as apheresis, ATRA (all-trans retinoic acid), steroids or hydrea while diagnostic work-up is being performed are allowed and not counted as a prior salvage. Supportive care therapy for MDS (growth factors, transfusions) will not be considered as prior therapy for MDS/AML and these patients will be enrolled to the frontline cohort of the study if they are otherwise eligible
• For relapsed or refractory cohort: Patients who have received at least one prior therapy for AML or for MDS (with \> 10%) blasts will be eligible. Patients may have received up to 4 salvage regimens for AML and/or MDS (defined by the International Prognostic Scoring System \[IPSS\] classification). Patients who receive MDS directed therapies considered not purely supportive such as hypomethylating agents (HMAs), lenalidomide, investigational therapies, will be enrolled to the salvage cohort if they are otherwise eligible
• In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of protocol therapy will be at least 2 weeks for cytotoxic agents or at least 5 half-lives for cytotoxic/noncytotoxic agents (whichever is shorter). The half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochure's, or drug-administration manuals) and will be documented in the protocol eligibility document. The use of chemotherapeutic or anti-leukemic agents is not permitted during the study with the following exceptions: (1) intrathecal (IT) therapy for patients with controlled central nervous system (CNS) leukemia at the discretion of the principal investigator (PI). (2) Use of cytarabine (up to 2 g/m\^2) or hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy. These medications will be recorded in the case-report form
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Serum biochemical values with the following limits unless considered due to leukemia
• Creatinine \< 1.8 mg/dl
• Total bilirubin \< 1.8 mg/dL, unless increase is due to hemolysis or congenital disorder
• Transaminases (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5x upper limit of normal (ULN)
• Potassium, magnesium, and calcium (normalized for albumin) levels should be within institutional normal limits
• Ability to take oral medication
• Ability to understand and provide signed informed consent
• Baseline left ventricular ejection fraction by echocardiogram (ECHO) or multigated acquisition scan (MUGA) \>= 50%
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential
• WOCBP must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy until at 30 days after the last dose of investigational drug. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as men with azoospermia do not require contraception. Appropriate methods of birth control include: birth control pills, condoms, intrauterine device (IUD), or other Food and Drug Administration (FDA) approved birth control methods
• Patients may be concurrently enrolling in supportive care clinical trials. Other investigational agents that are used for treatment of other cancers will not be allowed

Exclusion Criteria:

• Patients with known allergy or hypersensitivity to quizartinib, mannitol, CPX-351 or any of their components
• Patients with electrolyte abnormalities at study entry defined as follows: (a) Serum potassium \< 3.5 mEq/L despite supplementation, or \> 5.5 mEq/L. (b) Serum magnesium above or below the institutional normal limit despite adequate management. (c) Serum calcium (corrected for albumin levels) above or below institutional normal limit despite adequate management
• Patients with known significant impairment of gastrointestinal (GI) function or GI disease as determined by the investigator that may significantly alter the absorption of quizartinib
• Patients with any other known concurrent severe and/or uncontrolled medical condition including but not limited to diabetes, cardiovascular disease including hypertension, renal disease, or active uncontrolled infection, which as determined by the investigator could compromise participation in the study. Patients on active antineoplastic or radiation therapy for a concurrent malignancy at the time of screening. Maintenance therapy, hormonal therapy, or steroid therapy for well-controlled malignancy is allowed
• Patients with a known human immunodeficiency virus (HIV) infection (HIV testing is not required prior to enrollment)
• Patients with known positive hepatitis B or C infection by serology, with the exception of those with an undetectable viral load within 3 months. (Hepatitis B or C testing is not required prior to study entry). Subjects with serologic evidence of prior vaccination to hepatitis B virus (HBV) (i.e., hepatitis surface antigen \[HBs Ag\]-, and anti-HBs+) may participate
• Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) within 3 days prior to the initiation of study treatment
• Patients who have had any major surgical procedure within 14 days of day 1
• Impaired cardiac function including any of the following: (a) screening electrocardiogram (ECG) with a corrected QT (QTc) \> 450 msec. The QTc interval will be calculated by Fridericia's correction factor (QTcF) at screening and on day 6 prior to the first dose of quizartinib. The QTcF will be derived from the average QTcF in triplicate. If QTcF \> 450 msec on day 6, quizartinib will not be given
• Patients with congenital long QT syndrome
• History or presence of sustained ventricular tachycardia requiring medical intervention
• Any history of clinically significant ventricular fibrillation or torsades de pointes
• Known history of second or third degree heart block (may be eligible if the patient currently has a pacemaker)
• Sustained heart rate of \< 50/minute on pre-entry ECG
• Right bundle branch block + left anterior hemiblock (bifascicular block)
• Complete left bundle branch block
• Patients with myocardial infarction or unstable angina within 6 months prior to starting study drug
• Congestive heart failure (CHF) New York (NY) Heart Association class III or IV
• Atrial fibrillation documented within 2 weeks prior to first dose of study drug
• Patients who are actively taking a strong CYP3A4 inducing medication
• Patients who require treatment with concomitant drugs that prolong QT/QTc interval with the exception of antibiotics, antifungals, and antivirals that are used as standard of care to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject or if the Investigator believes that beginning therapy with a potentially QTc-prolonging medication (such as anti-emetic) is vital to an individual subject's care while on study
• Known family history of congenital long QT syndrome

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment

Not applicable

Masking

No masking

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Secondary measures

Research locations (1)

The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.

1 locations

Study team and timeline

Lead sponsor

M.D. Anderson Cancer Center

Study start

May 27, 2020 Actual

Primary completion

Dec 31, 2027 Estimated

Study completion

Dec 31, 2027 Estimated

First posted

Oct 16, 2019 Actual

Last updated

Nov 10, 2026 Actual

Official study contacts

No central contact is listed. Check the locations and the official record.