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

Phase 2

Completed

Conditions: Acute Myeloid Leukemia

Interventions: Drug: CPX-351
Drug: Intensive Salvage Therapy

Registration Number: NCT00822094

Lead Sponsor: Jazz Pharmaceuticals

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 126

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CPX-351 (Arm A)	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
Salvage Therapy (Arm B)	Intensive 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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Complete Remission Rate	Following 1st induction, following 2nd induction if applicable
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 Stem Cell Transplant	Up to 1 year from randomization	Number of patients transferred for stem cell transplant
Event Free Survival	Up to 1 year from randomization	Progression EFS median
Rate of Aplasia	Up to 1 year from randomization	Patients with Aplasia During Study

Trial Locations

Locations (42): Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
UCLA
🇺🇸
Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸
Los Angeles, California, United States
UC Davis Cancer Center
🇺🇸
Sacramento, California, United States
University of Colorado Cancer Center
🇺🇸
Aurora, Colorado, United States
Northwestern University Robert H. Lurie Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
University of Chicago Medical Center Section of Hematology/Oncology
🇺🇸
Chicago, Illinois, United States
St. Francis Cancer Center
🇺🇸
Beech Grove, Indiana, United States
University of Louisville Brown Cancer Center
🇺🇸
Louisville, Kentucky, United States
Scroll for more (32 remaining)
Arizona Cancer Center
🇺🇸Tucson, Arizona, United States