Patients Receiving Induction With Liposomal Daunorubicin and Cytarabine (CPX-351) for Acute Myeloid Leukemia

The Feasibility of Safely Managing Patients Receiving Induction With Liposomal Daunorubicin and Cytarabine (CPX-351) for Acute Myeloid Leukemia (AML) in an Outpatient Environment

This is a single-arm, single-site run-in phase (six subjects) followed by a multicenter continuation phase (114 subjects), Phase IV study. Eligible subjects will be receiving CPX-351 as their usual medical care administered according to FDA approval, as a condition for participation.

Study Overview

• Status: Terminated
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Behavioral: Outpatient Care Model; Drug: CPX-351

Detailed Description

This is an open-label, non-randomized study of a non-drug intervention in subjects receiving CPX-351 as their usual medical care administered according to its FDA approval. The study intervention is the application of a prescribed outpatient care model, including a nurse teacher educational program and quality of life surveys for both subjects and caregivers, in subjects who meet medical and logistical criteria. Induction therapy and medical follow-up are performed without prophylactic admission to an inpatient facility.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects with newly diagnosed acute myeloid leukemia who are eligible for treatment with CPX-351 therapy according to the FDA approval and indication: therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC).
2. Age ≥ 18 years
3. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 (or Karnofsky Performance Status equivalent of 70 or above).
4. Total bilirubin ≤ 3 mg/dL.
5. Creatinine clearance > 30 mL/min by Cockcroft/Gault equation.
6. Adequate cardiac function, as assessed by ejection fraction( ≥50% for anthracycline therapy) via multiple-gated acquisition (MUGA) or echocardiogram.
7. Total white blood cell count of ≤ 20,000/µL on peripheral blood assessment (hydrea and/or leukapheresis allowed).
8. No evidence of active, uncontrolled infection.
9. No evidence of clinically significant disseminated intervascular coagulation (DIC)
10. No clinically significant abnormalities in core vital signs like heart rate, blood pressure or oxygenation which require inpatient evaluation or monitoring.
11. In the opinion of the enrolling physician, the subject is not at risk for clinically significant tumor lysis syndrome based on clinical assessment, complete blood count (CBC), comprehensive metabolic panel (CMP), uric acid, and lactate dehydrogenase (LDH).
12. In the opinion of the enrolling physician, no medical conditions that preclude the subject or the primary caregiver from transportation to and from the outpatient clinical care facility.
13. Both subject and the identified primary caregiver(s) signed informed consent.
14. In the opinion of the enrolling physician, there are no medical contraindications to outpatient induction and management.

15. Male subjects, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the followings:

    • Practice effective barrier contraception during the entire study period and through six months after the last dose of CPX-351, OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)

Female subjects must meet one of the followings:

• Postmenopausal for at least one year before enrollment, OR
• Surgically sterile (i.e., undergone a hysterectomy or bilateral oophorectomy), OR
• If the subject is of childbearing potential (defined as not satisfying either of the above two criteria), she must agree to practice two acceptable methods of contraception (combination methods require use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive) from the time of signing of the informed consent form through six months after the last dose of CPX-351, OR o Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable contraception methods.)

Logistical Inclusion Criteria

1. The subject must be able to reside within approximately 45 minutes of the hospital where induction therapy is administered, during normal driving conditions (in the opinion of the enrolling physician), until count recovery or 60 days post-treatment, whichever comes first

2. The enrolling physician must verify and attest that the subject has a primary caregiver meeting all the following criteria:

   • Reside with the subject.
   • Be able to care for the subject full time or arrange to share full-time care with secondary caregivers.
   • Provide transportation.
   • Respond to clinical issues that arise.
   • Communicate with subject and physician in a timely manner.
3. The nurse teacher must verify that the subject and primary caregiver have completed and adequately understand the study-dictated nurse teacher educational program.
4. The nurse teacher must verify the subject and primary caregiver have capacity to comply with outpatient management program.
5. The subject must have reliable, working telephone access.
6. The subject must be willing and able to attend all protocol-dictated visits and be seen frequently as an outpatient at the clinical care facility where induction therapy is administered.

Exclusion Criteria:

1. Pregnant women (per pregnancy test in women of childbearing potential) or women who are breast-feeding.
2. Subjects currently receiving any investigational agents.
3. Subjects must not have current evidence of another malignancy that requires treatment.
4. Subjects diagnosed with Wilson's disease and/or copper-related metabolic disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention; The study intervention is the application of a prescribed outpatient care model including a nurse teacher educational program and quality of life surveys for both subjects and caregivers. Induction therapy and medical follow up are performed without prophylactic admission to an inpatient facility. Subjects will also receive CPX-351 according to FDA approval, to subjects who meet medical and logistical criteria for study enrollment.

Behavioral: Outpatient Care Model; Outpatient care model includes a nurse teacher educational program, scheduled outpatient visit protocol, and quality of life surveys for both subjects and caregivers.; Drug: CPX-351; CPX-351 is administered, according to FDA approval, to subjects who meet medical and logistical criteria for study enrollment.; Other Names: Cytarabine; Vyxeos®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Adherent to Recommendations	This measure will record the number subjects who adhere to outpatient follow-up appointments and readmission recommendations. Subjects completing 95% of their recommended outpatient visits will be considered to be adherent to the recommendations.	Day 60
Number of Participants Adherent to Readmission Recommendations	This measure will record the number of subjects who complete as 100% compliance with medical provider recommendations to be admitted to the hospital (except for reasons of adopting a palliative or hospice approach to care). Subjects not achieving a 100% rate of compliance will be considered non-adherent to the recommendations.	Day 60

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Investigators: Principal Investigator: Laura Michaelis, MD, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2019
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: June 12, 2019
• First Submitted That Met QC Criteria: June 12, 2019
• First Posted (Actual): June 17, 2019

Study Record Updates

• Last Update Posted (Actual): July 19, 2022
• Last Update Submitted That Met QC Criteria: July 17, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Outpatient; Leukemia; CPX-351; Vyxeos®
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cytarabine
• Other Study ID Numbers: PRO34597

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No