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

NCT04128748 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2019-0351NCI-2019-06051
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myeloid Leukemia; Recurrent Acute Myeloid Leukemia; Blasts More Than 10 Percent of Bone Marrow Nucleated Cells; High Risk Myelodysplastic Syndrome; Recurrent Myelodysplastic Syndrome; Refractory Acute Myeloid Leukemia; Refractory Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose

  Will follow standard reporting guidelines for adverse events, and summarize safety data by category, severity and frequency.

  Up to 28 days

• Complete remission (CRc) rate

  CRc and toxicity will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey (1995) as extended by Thall and Sung (1998). Will estimate the CRc rate for the combination treatment, along with the 95% credible interval.

  Up to 3 cycles (28 days in 1 cycle)

Secondary Outcomes (3)

• Duration of response (DOR)

  From the first documentation of CRc to disease recurrence, disease progression or death whichever occurs first, assessed up to 5 years

• Event-free survival

  From the date of treatment initiation to the date of documented treatment failure, relapses from CRc, or death from any cause,, whichever occurs first, assessed up to 5 years

• Overall survival

  From treatment start till death or last follow-up id the patients is alive, assessed up to 5 years

Study Arms (1)

Treatment (CPX-351, quizartinib)

EXPERIMENTAL

INDUCTION: Patients receive CPX-351 IV over 90 minutes on days 1, 3 and 5 and quizartinib PO on days 6-19. Patients who do not respond to treatment during cycle 1 receive CPX-351 IV on days 1 and 3 and quixartinib PO on days 6-19 during cycle 2. Treatment repeats every 28 days for up 2 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive CPX-351 over 90 minutes on days 1 and 3 and quizartinib PO on days 4-28 of cycle 1. Treatment with CPX-351 repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive quizartinib PO on days 1-28 in the absence of disease progression or unacceptable toxicity.

Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Drug: Quizartinib

Interventions

Liposome-encapsulated Daunorubicin-Cytarabine DRUG

Given IV

Also known as: CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, Vyxeos

Treatment (CPX-351, quizartinib)

Quizartinib DRUG

Given PO

Also known as: AC-220, AC010220, AC220

Treatment (CPX-351, quizartinib)

Eligibility Criteria

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

You may qualify if:

• 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%

You may not qualify if:

• 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)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• Jentzsch M, Grimm J, Bill M, Brauer D, Backhaus D, Goldmann K, Schulz J, Niederwieser D, Platzbecker U, Schwind S. ELN risk stratification and outcomes in secondary and therapy-related AML patients consolidated with allogeneic stem cell transplantation. Bone Marrow Transplant. 2021 Apr;56(4):936-945. doi: 10.1038/s41409-020-01129-1. Epub 2020 Nov 19.

  PMID: 33208914 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

CPX-351; Injections; Cytarabine; quizartinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Musa Yilmaz

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Musa Yilmaz

CONTACT

713-745-9945; myilmaz@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2019
• First Posted: October 16, 2019
• Study Start: May 27, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)