Vyxeos for Re-induction Treatment of Acute Myeloid Leukemia Patients With Persistent Disease After Induction

NCT04049539 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-19060NCI-2019-04724
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies the side effects and how well Vyxeos works in treating patients with intermediate and high-risk acute myeloid leukemia who have failed an initial cycle of standard cytarabine and daunorubicin chemotherapy. Vyxeos is a combination of both chemotherapy drugs cytarabine and daunorubicin contained in a liposome. Drugs used in chemotherapy, such as cytarabine and daunorubicin, work 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. Cytarabine and daunorubicin given together in liposomes may have fewer side effects and work better than cytarabine and daunorubicin given alone in patients with acute myeloid leukemia.

Conditions

Blasts More Than 5 Percent of Bone Marrow Nucleated Cells; Persistent Disease; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Will be measured by the time to count recovery, incidence of symptomatic cardiac dysfunction, incidence of hepatic or renal toxicity, incidence of severe hemorrhage, and incidence of severe infection. Will be summarized by National Cancer Institute Common Terminology Criteria for Adverse Events version 4, and frequency counts will be tabulated with a focus on severe (grade 3+) adverse events and toxicities that are deemed at least possibly related to study treatment. The incidence of specific toxicities will be calculated as the proportion of patients experience these toxicities over all patients who receive any study drug.

  Up to 60 days

• Calculation rate of complete response (CR) and complete response with incomplete hematologic recovery (CRi)

  CR and CRi rate will be defined as the proportion of patients who achieve CR or CRi over all evaluable patients. The rates will be provided with 95% binomial confidence intervals.

  Up to 2 years

Secondary Outcomes (2)

• Progression-free survival

  Up to 2 years

• Overall survival

  From the date of the first dose of study treatment to death from any cause, up to 2 years

Other Outcomes (4)

• Measurement of blast cell cycle fraction

  Baseline up to day 42

• Relative clearance immunophenotypically abnormal blast and stem cells

  Up to day 42

• Efficacy of blast cell and leukemia stem/repopulating cell (LSC) elimination

  Up to day 42

Study Arms (1)

Treatment (liposome-encapsulated daunorubicin-cytarabine)

EXPERIMENTAL

Within 14-33 days after the start of previous cycle of chemotherapy, patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity.

Drug: Liposome-encapsulated Daunorubicin-Cytarabine

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 (liposome-encapsulated daunorubicin-cytarabine)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be able to provide written informed consent
• Patients must have a diagnosis of acute myeloid leukemia
• Patients must have received standard induction chemotherapy (cytarabine 100-200mg/m2 by continuous infusion on days 1-7 and either daunorubicin 45-90mg/m2 or idarubicin 10-12mg/ m2 daily for 3 days during days 1-7) within the 14-33 days prior to starting trial treatment and have documented persistent disease (13-29 days from the start of 7+3 treatment). Patients who have received a 7+3 regimen utilizing gemtuzumab ozogamicin may enroll. Patients who received lower doses of the above agents due to appropriate adjustments for reduced renal or hepatic clearance may also enroll. Persistent disease will be defined as bone marrow cellularity of \>10-20% and bone marrow blast percentage of \>5-10% or clear evidence of immunophenotypically aberrant leukemia cells in the bone marrow. The final determination of persistent AML will be made by the treating physician, but must meet NCCN criteria for persistent disease1. Enrollment of patients with less than 20% cellularity or less than 10% blasts will require approval of the principal investigator. Patients who received concomitant treatment with another targeted therapy for AML that is FDA-approved for administration with 7+3 (e.g. midostaurin) may enroll and can continue to receive this treatment (according to the FDA-approved 7+3 re-induction dosing schedule) during Vyxeos treatment.
• Patients must be deemed by the treating physician to be unlikely to achieve complete response (CR) without further therapy
• Patients must be deemed by the treating physician to be able to tolerate intensive chemotherapy (similar to 7+3 chemotherapy)
• Normal left ventricular ejection fraction (\>= 50% by echocardiography or multi-gated acquisition radionuclide angiocardiography \[MUGA\]) and lifetime daunorubicin dose of less than 462mg/m\^2 (including recent course of 7+3), or equivalent doses of another anthracycline medications. (This is 550mg/m\^2 \[maximum lifetime dose\] minus 88mg/m\^2 \[planned dose of Vyxeos on study\].)
• Eastern Cooperative Oncology Group (ECOG) functional status of 0, 1, or 2
• Aspartate aminotransferase (AST) \< 5 x upper limit of normal (ULN) for the local laboratory
• Alanine aminotransferase (ALT) \< 5 x ULN for the local laboratory
• Total bilirubin \< 1.5 x ULN (except for patients with known Gilbert?s syndrome) for the local laboratory
• Calculated creatinine clearance (according to the Cockcroft-Gault equation) \> 40 mL/min OR serum creatinine \< 1.5 x the ULN for the local laboratory
• Female patients of childbearing potential must agree to use two forms of contraception from screening visit until 6 months following the last dose of study treatment. Female patients must have a documented negative pregnancy test
• Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use two forms of contraception from screening visit until 6 months after the last dose of study treatment. They must also refrain from sperm donation from screening visit until 6 months following the last dose of study treatment

You may not qualify if:

• Acute promyelocytic leukemia (or M3 AML)
• Patients known to have core binding factor AML (defined as presence of t(8;21), inv(16), or other cytogenetically equivalent abnormalities)
• Patients known to have inactivating mutations of TP53 or evidence of an absence of p53 protein activity as indicated by a monosomal karyotype. Monosomal karyotype will be defined as two or more monosomies (loss of an entire chromosome or the entire long arm of a chromosome \[such as 7q-\]) or a single monosomy in the setting of a complex karyotype. Patients with a complex karyotype without a monosomy are eligible to enroll
• Patients that the treating physician does not feel are able to tolerate intensive chemotherapy
• History of serious (\>= grade 3) hypersensitivity reaction to cytarabine, daunorubicin, or any component of the formulation
• Known Wilson's disease or other symptomatic abnormality of copper metabolism (laboratory screening is not required in the absence of clinical or historical evidence of Wilson's disease or other problems of copper metabolism)
• Total lifetime daunorubicin dose of more than 462 mg/m\^2 (including recent course of 7+3) or equivalent total doses of other anthracycline medications. (This is 550mg/m\^2 maximum dose - 88mg/m\^2 planned dose of Vyxeos on study.)
• Pregnancy or inability to use highly effective method of contraception for 6 months following last dose of Vyxeos. Potentially fertile patients must have documented negative serum pregnancy test. Breastfeeding should be avoided for at least 14 days after the last dose Vyxeos
• Patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control. As infection is a common feature of AML, patients with active infections are permitted to enroll provided that the infection is under control
• Patients who have received an investigational agent (for any indication) within 5 half-lives of the agent and until toxicity from this has resolved to grade 1 or less; if the half-life of the agent is unknown, patients must wait 4 weeks prior to first dose of study treatment. An investigational agent is one for which there is no approved indication by the United States (US) Food and Drug Administration (FDA)
• Patients with psychological, familial, social, or geographic factors that otherwise preclude them from giving informed consent, following the protocol, or potentially hamper compliance with study treatment and follow-up
• Any other significant medical condition, including psychiatric illness or laboratory abnormality, that would preclude the patient participating in the trial or would confound the interpretation of the results of the trial
• Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Other malignancy currently requiring active therapy (except minor surgery for non-melanoma skin cancer and for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer)

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead

Study Sites (2)

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

CPX-351; Injections; Cytarabine

Condition Hierarchy (Ancestors)

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

• Gregory K Behbehani, MD, PhD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

1-800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 6, 2019
• First Posted: August 8, 2019
• Study Start: January 29, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)