Trial of CPX-351 in Newly Diagnosed Elderly AML Patients

Phase IIB, Multicenter, Randomized, Open Label Trial of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection Versus Cytarabine and Daunorubicin in Patients With Untreated AML 60-75 Years of Age.

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00788892

Enrollment

126

Registered

2008-11-11

Start date

2008-10-31

Completion date

2011-12-31

Last updated

2018-01-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Myeloid Leukemia

Keywords

Acute, Myeloid, Leukemia, elderly, Newly, Diagnosed

Brief summary

The study investigates if CPX-351 will be a) more effective than the standard AML treatment and b) more tolerable than the standard AML treatment regimens. The study compares the investigational product CPX-351 vs the standard treatment for AML in this patients age group.

Detailed description

This study is a randomized, open-label, parallel-arm, fixed-dose, standard therapy controlled Phase IIB trial. Study enrollment duration is expected to be approximately 12-18 months. On entry, patients are randomized to receive either CPX-351 or standard induction treatment with cytarabine and daunorubicin(7 and 3 regimen). Patients are stratified to balance the likelihood of obtaining a CR and the duration of CR between the two arms.

Interventions

DRUGCPX-351

DRUGCytarabine

DRUGDaunorubicin

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

60 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Age ≥60 and \<76 years at the time of diagnosis of AML * Pathological confirmation of AML * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Able to adhere to the study visit schedule and other protocol requirements * Laboratory values fulfilling the following: Serum creatinine \< 2.0 mg/dL Serum total bilirubin \< 2.0 mg/dL Serum alanine aminotransferase or aspartate aminotransferase \< 150 IU/liter Note: If elevated liver enzymes are related to disease; contact medical monitor to discuss. * Cardiac ejection fraction \> 50% by echocardiography or MUGA scan

Exclusion criteria

* Patients with locally advanced or metastatic solid tumors ≤5 years from initial diagnosis are excluded. (Patients with locally advanced or metastatic solid tumors \>5 years from initial diagnosis, for whom the investigator has no clinical suspicion of active disease for \>2 years before randomization are eligible) * Prior treatment for AML; only hydroxyurea is permitted (see below) * Acute promyelocytic leukemia \[t(15;17)\] or favorable cytogenetics, including t(8;21) or inv16 if known at the time of randomization * Patients with a prior anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent) * Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent * Administration of any antineoplastic therapy within 4 weeks of the first CPX-351 dose; in the event of rapidly proliferative disease use of hydroxyurea is permitted until 24 hours before the start of study treatment * Clinical evidence of active CNS leukemia * Patients with history of and/or current evidence of myocardial impairment (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Class III or IV staging * Active and uncontrolled infection. Patients with an infection receiving treatment with antibiotics may be entered into the study if they are afebrile and hemodynamically stable for 72 hrs. * Current evidence of invasive fungal infection (blood or tissue culture); HIV or active hepatitis C infection * Hypersensitivity to cytarabine, daunorubicin or liposomal products * History of Wilson's disease or other copper-related disorder

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Complete Remission	Within 6 weeks of the last induction treatment	Response was defined according to International Working Group Criteria (Cheson, et al. 2003) which requires peripheral blood neutrophils of \>1000/µL and peripheral blood platelets of \>100,000/µL in the absence of bone marrow blasts.

Secondary

Measure	Time frame	Description
Remission Duration/Time to Remission	Following achievement of CR over the study period	Remission Duration was assessed from the time measurement criteria for CR were met until the first date that disease relapse was objectively documented or the subject died. Time to remission was measured from the date of randomization to the time measurement criteria for CR were first met.
Event Free Survival	Up to 1 year from randomization	Event-free survival begins from randomization to the date persistent disease is documented or date of relapse after CR, or death, whichever comes first.
Overall Survival Rate at 1 Year	1 year	Survival defined as the time from randomization to death.
Rate of Stem Cell Transplant	Up to 1 year	The rate of patients who underwent stem cell transplant.
Aplasia Rate	Day 14 (1st Induction)	Bone marrow aplasia was defined as \<20% cellularity and 5% blasts in the bone marrow aspiration evaluation.

Countries

Canada, United States

Participant flow

Participants by arm

Arm	Count
Arm A: CPX-351 First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3	85
Arm B: Cytarabine + Daunorubicin First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice	41
Total	126

Baseline characteristics

Characteristic	Arm A: CPX-351	Arm B: Cytarabine + Daunorubicin	Total
Age, Continuous	67.8 years STANDARD_DEVIATION 4.63	68.2 years STANDARD_DEVIATION 4.88	67.9 years STANDARD_DEVIATION 4.69
Sex: Female, Male Female	32 Participants	16 Participants	48 Participants
Sex: Female, Male Male	53 Participants	25 Participants	78 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	85 / 85	41 / 41
serious Total, serious adverse events	47 / 85	16 / 41

Outcome results

Primary

Number of Participants With Complete Remission

Response was defined according to International Working Group Criteria (Cheson, et al. 2003) which requires peripheral blood neutrophils of \>1000/µL and peripheral blood platelets of \>100,000/µL in the absence of bone marrow blasts.

Time frame: Within 6 weeks of the last induction treatment

Population: Efficacy Evaluable Analysis Set: All randomized subjects who received at least 1 dose of study drug. One subject who developed Philadelphia chromosome positive disease prior to any efficacy assessment was excluded from the Efficacy Analysis Set.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Arm A: CPX-351	Number of Participants With Complete Remission	41 Participants
Arm B: Cytarabine + Daunorubicin	Number of Participants With Complete Remission	20 Participants

Secondary

Aplasia Rate

Bone marrow aplasia was defined as \<20% cellularity and 5% blasts in the bone marrow aspiration evaluation.

Time frame: Day 14 (1st Induction)