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

Phase 2
Recruiting
Conditions
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Acute Myeloid Leukemia With Myelodysplasia-Related Changes
Secondary Acute Myeloid Leukemia
Therapy-Related Acute Myeloid Leukemia
Interventions
Drug: Liposome-encapsulated Daunorubicin-Cytarabine
Registration Number
NCT04269213
Lead Sponsor
Roswell Park Cancer Institute
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
46
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (CPX-351)Liposome-encapsulated Daunorubicin-CytarabineINDUCTION: 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.
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Event free survivalTime 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.

Incidence of adverse eventsUp to 5 years

Will be reported by grade using frequencies and relative frequencies.

Overall survivalTime 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.

CR + CRi durationTime 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.

Allogeneic hematopoietic cell transplant rateUp to 5 years

Transplant rate estimated using a 90% confidence interval obtained using Jeffrey's prior method.

Trial Locations

Locations (4)

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

SUNY Upstate Medical Center

🇺🇸

Syracuse, New York, United States

Allegheny Health Network Cancer Institute - West Penn Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

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