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

Sponsor

Roswell Park Cancer Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04269213

Collaborator

Jazz Pharmaceuticals (Industry)

Enrollment

Locations

Arm

Anticipated Duration (Months)

15.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Acute Myeloid Leukemia With Myelodysplasia-Related Changes Secondary Acute Myeloid Leukemia Therapy-Related Acute Myeloid Leukemia	Drug: Liposome-encapsulated Daunorubicin-Cytarabine	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

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:

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

46 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of CPX-351 in Younger Patients < 60 Years Old With Secondary Acute Myeloid Leukemia

Actual Study Start Date :

Jul 29, 2021

Anticipated Primary Completion Date :

Jan 29, 2024

Anticipated Study Completion Date :

Jan 29, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (CPX-351) 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.	Drug: Liposome-encapsulated Daunorubicin-Cytarabine Given IV Other Names: CPX-351 Cytarabine-Daunorubicin Liposome for Injection Liposomal AraC-Daunorubicin CPX-351 Liposomal Cytarabine-Daunorubicin Liposome-encapsulated Combination of Daunorubicin and Cytarabine Vyxeos

Arm

Intervention/Treatment

Experimental: Treatment (CPX-351)

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.

Drug: Liposome-encapsulated Daunorubicin-Cytarabine

Given IV

Other Names:

CPX-351

Cytarabine-Daunorubicin Liposome for Injection

Liposomal AraC-Daunorubicin CPX-351

Liposomal Cytarabine-Daunorubicin

Liposome-encapsulated Combination of Daunorubicin and Cytarabine

Vyxeos

Outcome Measures

Primary Outcome Measures

Complete response rate (morphological complete remission [CR] and incomplete blood count recovery [CRi]) [At day 45]
Defined by the International Working Group Criteria. Will be summarized using frequencies and relative frequencies.

Secondary Outcome Measures

CR + CRi duration [Time from CR or CRi until relapse or last follow-up, assessed up to 5 years]
Will be summarized using standard Kaplan-Meier methods, where estimates of the median obtained with 90% confidence intervals.
Event free survival [Time from treating until disease progression/relapse, death due to disease, or last follow-up, assessed up to 5 years]
Will be summarized using standard Kaplan-Meier methods, where estimates of the median obtained with 90% confidence intervals.
Overall survival [Time from treatment until death due to any cause or last follow-up, assessed up to 5 years]
Will be summarized using standard Kaplan-Meier methods, where estimates of the median obtained with 90% confidence intervals.
Allogeneic hematopoietic cell transplant rate [Up to 5 years]
Transplant rate estimated using a 90% confidence interval obtained using Jeffrey's prior method.
Incidence of adverse events [Up to 5 years]
Will be reported by grade using frequencies and relative frequencies.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 59 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
2	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
3	Allegheny Health Network Cancer Institute - West Penn Hospital	Pittsburgh	Pennsylvania	United States	15224