Trial of CPX-351 in Adult Patients With First Relapse Acute Myeloid Leukemia (AML)

Phase IIB, Multicenter, Randomized, Open-Label Trial Of CPX-351 (Cytarabine : Daunorubicin) Liposome Injection Versus Intensive Salvage Therapy In Adult Patients ≤ 65 Years Old With AML In First Relapse Following An Initial CR > 1 Month Duration

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00822094

Enrollment

126

Registered

2009-01-14

Start date

2009-02-28

Completion date

2012-01-31

Last updated

2017-11-24

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, Adult, First, Relapse, AML, Acute Myelogenous leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute, Acute myelocytic leukemia

Brief summary

The study investigates if CPX-351 will be a) more effective than the standard intensive salvage AML treatment and b) more tolerable than the standard intensive salvage treatment regimens. The study compares the investigational product CPX-351 vs the standard intensive salvage treatment for first relapse AML patients.

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 intensive first salvage treatment. Patients are stratified to balance the likelihood of obtaining a CR and the duration of CR between the two arms.

Interventions

DRUGCPX-351

DRUGIntensive Salvage Therapy

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Ability to understand and voluntarily sign an informed consent form * Age ≥18 and ≤65 years at the time of relapse * Pathological confirmation of relapsed AML after initial CR of \>1 month duration * 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 \<3xULN Note: If elevated liver enzymes are related to disease; contact medical monitor to discuss. * Cardiac ejection fraction \> 50% by echocardiography or MUGA scan * All men and women must agree to practice effective contraception during the study period and for 3 months afterward if not otherwise documented to be infertile.

Exclusion criteria

* Patients with active second malignancies are excluded. Patients with second malignancies in remission may be eligible if there is no clinical evidence of active disease, documented by imaging, with tumor marker studies, etc., at screening. Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are eligible. In all cases, the second malignancy and its non-chemotherapy treatment must not interfere with the investigators ability to assess the safety or efficacy of the study treatment * Patients with acute promyelocytic leukemia \[t(15;17)\] * Total lifetime anthracycline exposure exceeding the equivalent of 368 mg/m2 of daunorubicin (or equivalent) prior to start of study therapy * Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent * Administration of any antineoplastic therapy within 4 weeks of therapy; intended to treat first relapse. 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 New York Heart Association Class III or IV staging * Active and uncontrolled infection. Patients with a bacterial 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); active hepatitis C infection or known HIV infection * Hypersensitivity to cytarabine, daunorubicin or liposomal products * History of Wilson's disease or other copper-related disorder * Patients with a history of severe toxicity related to receiving conventional dose cytarabine in first line treatment (approximately 100mg/m2/d for \<7 days) are excluded. Patients who experienced unacceptable toxicities while receiving high dose cytarabine (approximately 3000mg/m2 for 6 doses) will not be treated again with the same regimen, but could be randomized to treatment with conventional dose cytarabine regimens where the risk of major toxicity is less. * Woman who are pregnant or breast feeding

Design outcomes

Primary

Measure	Time frame	Description
Proportion of Subjects Surviving at 1 Year	Up to 1 year from randomization	The proportion of subjects surviving at 1 year was evaluated separately for each arm by the number of subjects alive at 1 year divided by the total number of subjects.

Secondary

Measure	Time frame	Description
Complete Remission Rate	Following 1st induction, following 2nd induction if applicable	—
Event Free Survival	Up to 1 year from randomization	Progression EFS median
Remission Duration	Following achievement of CR and up to 1 year from randomization	Remission duration was measured from the time the criteria for CR were first met until the first date that disease relapse was objectively documented or until subject death.
Rate of Aplasia	Up to 1 year from randomization	Patients with Aplasia During Study
Rate of Stem Cell Transplant	Up to 1 year from randomization	Number of patients transferred for stem cell transplant

Countries

Canada, France, Poland, United States

Participant flow

Participants by arm

Arm	Count
CPX-351 First induction: 100 units/m2 on Days 1, 3, and 5 by 90-minute IV infusion Second induction: 100 units/m2 on Days 1 and 3 by 90-minute IV infusion Consolidation(s): 100 units/m2 on Days 1 and 3 by 90-minute IV infusion	81
Salvage Therapy First induction: Investigator's choice salvage therapy administered according to local practice Second induction: Investigator's choice salvage therapy administered according to local practice Consolidation(s): Investigator's choice consolidation therapy administered according to local practice	44
Total	125

Baseline characteristics

Characteristic	CPX-351	Salvage Therapy	Total
Age, Continuous	49.4 years STANDARD_DEVIATION 11.57	51.8 years STANDARD_DEVIATION 11.54	50.2 years STANDARD_DEVIATION 11.57
Sex: Female, Male Female	43 Participants	25 Participants	68 Participants
Sex: Female, Male Male	38 Participants	19 Participants	57 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	81 / 81	44 / 44
serious Total, serious adverse events	53 / 81	22 / 44

Outcome results

Primary

Proportion of Subjects Surviving at 1 Year

The proportion of subjects surviving at 1 year was evaluated separately for each arm by the number of subjects alive at 1 year divided by the total number of subjects.

Time frame: Up to 1 year from randomization

Population: Efficacy Evaluable Analysis Set - All randomized participants who received at least one dose of study medication.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
CPX-351	Proportion of Subjects Surviving at 1 Year	29 Participants
Salvage Therapy	Proportion of Subjects Surviving at 1 Year	12 Participants

Secondary