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CPX-351 for the Treatment of Secondary Acute Myeloid Leukemia in Patients Younger Than 60 Years Old

Primary Purpose

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Acute Myeloid Leukemia With Myelodysplasia-Related Changes, Secondary Acute Myeloid Leukemia

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Liposome-encapsulated Daunorubicin-Cytarabine
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Eligibility Criteria

18 Years - 59 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Newly diagnosed:

    • Therapy-related acute myeloid leukemia (AML)
    • AML with antecedent myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML)
    • AML with MDS-related changes (as per World Health Organization [WHO])
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Plasma creatinine =< 1.5 x upper limit of normal (ULN)
  • Total bilirubin < 2.0 mg/dL
  • Serum alanine aminotransferase and aspartate aminotransferase < 3 x ULN
  • Left ventricular ejection fraction by echocardiogram or multiple-gated acquisition >= 50%
  • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to enrollment and commit to two forms of birth control
  • Men must use a latex condom during any sexual contact with women of childbearing potential
  • Willing to adhere to protocol specific requirements
  • Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

  • Prior treatment of AML
  • Known clinically active central nervous system (CNS) leukemia
  • Core-binding factor leukemia
  • Acute promyelocytic leukemia
  • Uncontrolled other malignancy
  • Prior anthracycline exposure > 368 mg/m^2 of daunorubicin or equivalent
  • Cardiovascular disease resulting in heart failure (New York Heart Association class III or IV), unstable angina (angina symptoms at rest), or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
  • Hypersensitivity to cytarabine, daunorubicin, or liposomal drugs
  • Known active HIV infection
  • Known history of active hepatitis B or C infection
  • Pre-existing liver disease (e.g. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis)
  • Evidence of ongoing, uncontrolled systemic infection
  • Pregnant or breastfeeding women
  • Subject with concurrent severe and/or uncontrolled medical or psychiatric conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy
  • History of Wilson disease or other copper-handling disorders
  • Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Sites / Locations

  • University of Nebraska Medical CenterRecruiting
  • Roswell Park Cancer InstituteRecruiting
  • Allegheny Health Network Cancer Institute - West Penn HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (CPX-351)

Arm Description

INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. RE-INDUCTION: Patients who do not achieve remission receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Beginning 5-8 weeks after the start of the last induction, patients who achieve CR receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 45 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Complete response rate (morphological complete remission [CR] and incomplete blood count recovery [CRi])
Defined by the International Working Group Criteria. Will be summarized using frequencies and relative frequencies.

Secondary Outcome Measures

CR + CRi duration
Will be summarized using standard Kaplan-Meier methods, where estimates of the median obtained with 90% confidence intervals.
Event free survival
Will be summarized using standard Kaplan-Meier methods, where estimates of the median obtained with 90% confidence intervals.
Overall survival
Will be summarized using standard Kaplan-Meier methods, where estimates of the median obtained with 90% confidence intervals.
Allogeneic hematopoietic cell transplant rate
Transplant rate estimated using a 90% confidence interval obtained using Jeffrey's prior method.
Incidence of adverse events
Will be reported by grade using frequencies and relative frequencies.

Full Information

First Posted
February 11, 2020
Last Updated
September 19, 2023
Sponsor
Roswell Park Cancer Institute
Collaborators
Jazz Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04269213
Brief Title
CPX-351 for the Treatment of Secondary Acute Myeloid Leukemia in Patients Younger Than 60 Years Old
Official Title
A Phase II Study of CPX-351 in Younger Patients &lt; 60 Years Old With Secondary Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 29, 2021 (Actual)
Primary Completion Date
January 29, 2025 (Anticipated)
Study Completion Date
January 29, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
Jazz Pharmaceuticals

4. Oversight

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.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies how well liposome-encapsulated daunorubicin-cytarabine (CPX-351) works in treating patients with secondary acute myeloid leukemia who are younger than 60 years old. Drugs used in chemotherapy, such as CPX-351, 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.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the complete response rate including morphologic complete remission (CR) and morphologic complete remission with incomplete blood count recovery (CRi) as defined by the International Working Group Criteria. SECONDARY OBJECTIVE: I. To determine CR + CRi duration, event free survival (EFS), overall survival (OS), patients successfully proceeding to allogenic hematopoietic cell transplant, and adverse events (AE). OUTLINE: INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. RE-INDUCTION: Patients who do not achieve remission receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Beginning 5-8 weeks after the start of the last induction, patients who achieve CR receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 45 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, and then every 3 months for up to 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Acute Myeloid Leukemia With Myelodysplasia-Related Changes, Secondary Acute Myeloid Leukemia, Therapy-Related Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
46 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (CPX-351)
Arm Type
Experimental
Arm Description
INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. RE-INDUCTION: Patients who do not achieve remission receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Beginning 5-8 weeks after the start of the last induction, patients who achieve CR receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 45 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Liposome-encapsulated Daunorubicin-Cytarabine
Other Intervention Name(s)
CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, Vyxeos
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Complete response rate (morphological complete remission [CR] and incomplete blood count recovery [CRi])
Description
Defined by the International Working Group Criteria. Will be summarized using frequencies and relative frequencies.
Time Frame
At day 45
Secondary Outcome Measure Information:
Title
CR + CRi duration
Description
Will be summarized using standard Kaplan-Meier methods, where estimates of the median obtained with 90% confidence intervals.
Time Frame
Time from CR or CRi until relapse or last follow-up, assessed up to 5 years
Title
Event free survival
Description
Will be summarized using standard Kaplan-Meier methods, where estimates of the median obtained with 90% confidence intervals.
Time Frame
Time from treating until disease progression/relapse, death due to disease, or last follow-up, assessed up to 5 years
Title
Overall survival
Description
Will be summarized using standard Kaplan-Meier methods, where estimates of the median obtained with 90% confidence intervals.
Time Frame
Time from treatment until death due to any cause or last follow-up, assessed up to 5 years
Title
Allogeneic hematopoietic cell transplant rate
Description
Transplant rate estimated using a 90% confidence interval obtained using Jeffrey's prior method.
Time Frame
Up to 5 years
Title
Incidence of adverse events
Description
Will be reported by grade using frequencies and relative frequencies.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Newly diagnosed: Therapy-related acute myeloid leukemia (AML) AML with antecedent myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) AML with MDS-related changes (as per World Health Organization [WHO]) Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 Plasma creatinine =< 1.5 x upper limit of normal (ULN) Total bilirubin < 2.0 mg/dL Serum alanine aminotransferase and aspartate aminotransferase < 3 x ULN Left ventricular ejection fraction by echocardiogram or multiple-gated acquisition >= 50% Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to enrollment and commit to two forms of birth control Men must use a latex condom during any sexual contact with women of childbearing potential Willing to adhere to protocol specific requirements Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Prior treatment of AML Known clinically active central nervous system (CNS) leukemia Core-binding factor leukemia Acute promyelocytic leukemia Uncontrolled other malignancy Prior anthracycline exposure > 368 mg/m^2 of daunorubicin or equivalent Cardiovascular disease resulting in heart failure (New York Heart Association class III or IV), unstable angina (angina symptoms at rest), or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months Hypersensitivity to cytarabine, daunorubicin, or liposomal drugs Known active HIV infection Known history of active hepatitis B or C infection Pre-existing liver disease (e.g. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis) Evidence of ongoing, uncontrolled systemic infection Pregnant or breastfeeding women Subject with concurrent severe and/or uncontrolled medical or psychiatric conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy History of Wilson disease or other copper-handling disorders Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amanda C Przespolewski
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vijaya Bhatt, MD
Phone
402-559-8500
Email
vijaya.bhatt@unmc.edu
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda C. Przespolewski
Phone
716-845-3287
Email
amanda.przespolewski@roswellpark.org
First Name & Middle Initial & Last Name & Degree
Amanda C. Przespolewski
Facility Name
Allegheny Health Network Cancer Institute - West Penn Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Salman Fazal, MD
Phone
412-578-4484
Email
Salman.Fazal@ahn.org

12. IPD Sharing Statement

Learn more about this trial

CPX-351 for the Treatment of Secondary Acute Myeloid Leukemia in Patients Younger Than 60 Years Old

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