Clinical trial NCT01804101: Liposomal Cytarabine-Daunorubicin CPX-351 in Treating Patients With Untreated Myelodysplastic Syndrome or Acute Myeloid Leukemia
Official title: Liposomal Cytarabine and Daunorubicin (CPX-351) for Adults With Untreated High-Risk MDS and Non-APL AML at High Risk of Treatment-Related Mortality
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Biphenotypic Leukemia
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Untreated Adult Acute Myeloid Leukemia
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-03-05
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized clinical trial studies liposomal cytarabine-daunorubicin CPX-351 in treating patients with untreated myelodysplastic syndrome or acute myeloid leukemia. Drugs used in chemotherapy, such as liposomal cytarabine-daunorubicin 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 OBJECTIVES:

I. Estimate whether the 32 units/m\^2 or the 64 units/m\^2 or both dose levels of CPX-351 (liposomal cytarabine-daunorubicin CPX-351) are likely to improve treatment-related mortality (TRM) rate while keeping the complete remission (CR) rate constant in patients with untreated high-risk myelodysplastic syndrome (MDS) or non-acute promyelocytic leukemia (APL) acute myeloid leukemia (AML) at high risk of TRM.

SECONDARY OBJECTIVES:

I. Describe the CR/CR with incomplete platelet count recovery (CRp) rate after up to 4 cycles of induction/re-induction therapy.

II. Describe the event-free survival, disease-free survival, and overall survival of patients who achieve CR/CRp.

III. Estimate the frequency and severity of regimen-associated toxicities.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I:

INDUCTION/RE-INDUCTION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation.

CONSOLIDATION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM II: (closed to accrual effective 4/21/14) INDUCTION/RE-INDUCTION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation.

CONSOLIDATION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 month.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of untreated "high-risk" MDS (\>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; patients with biphenotypic AML are eligible; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution and cytogenetic/molecular information is available

  * Prior hydroxyurea for AML is permitted but should be discontinued prior to start of CPX-351 treatment
  * Azacitidine, decitabine, lenalidomide, and growth factors are permitted for low-risk MDS (\< 10% blasts); all treatments for MDS should be discontinued prior to start of CPX-351 treatment
* Treatment-related mortality (TRM) score \>= 13.1 as calculated with simplified model
* Bilirubin \< 2.0 mg/mL x upper limit of normal; this requirement reflects the excretion of CPX-351 by the liver
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 4.0 x upper limit of normal; this requirement reflects the excretion of CPX-351 by the liver
* Left ventricular ejection fraction (LVEF) \>= 40%, assessed within 28 days prior to registration, e.g. by multi gated acquisition (MUGA) scan or echocardiography, or other appropriate diagnostic modality
* Patients with symptoms/signs of hyperleukocytosis or white blood cell (WBC) \> 100,000/uL can be treated with leukapheresis prior to enrollment
* Provide signed written informed consent

Exclusion Criteria:

* Refractory/relapsing blast crisis of chronic myelogenous leukemia (CML)
* Concomitant illness associated with a likely survival of \< 1 year
* Active systemic fungal, bacterial, viral, or other infection, unless under treatment with anti-microbials and controlled/stable, as defined as being afebrile and hemodynamically stable for 24-48 hours

Primary outcomes:
measure: Treatment-related Mortality Rate. (TRM)
timeFrame: Up to 1 month after completion of study treatment
Secondary outcomes:
measure: Overall Remission Rate (CR+CRp)
timeFrame: Up to day 28
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Roland Walter
role: PRINCIPAL_INVESTIGATOR
References: