Study of Elacytarabine Versus Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia (AML) (CLAVELA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Clavis Pharma
ClinicalTrials.gov Identifier:
NCT01147939
First received: April 14, 2010
Last updated: September 20, 2013
Last verified: September 2013
  Purpose

The purpose of the study is to assess the efficacy and safety of elacytarabine versus investigator's choice treatment in patients with relapsed or refractory acute myeloid leukemia (AML).


Condition Intervention Phase
Acute Myeloid Leukemia (AML)
Drug: Elacytarabine
Drug: Investigator's Choice
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Phase III Study of Elacytarabine vs. Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia

Resource links provided by NLM:


Further study details as provided by Clavis Pharma:

Primary Outcome Measures:
  • Overall survival [ Time Frame: Until 300 events occur ] [ Designated as safety issue: No ]
    Time from date of randomisation until the date of death


Secondary Outcome Measures:
  • Remission rate [ Time Frame: Until 300 events occur ] [ Designated as safety issue: No ]
    • Remission rate measured by overall response rate (ORR) (i.e. complete remission (CR) and complete remission with incomplete bone marrow recovery (CRi))
    • Remission rate measured by CR
    • Remission duration analysed using cumulative incidence of relapse (CIR) measured from date of CR or CRi

  • Compare number of patients with adverse events (AEs) per study arm as a measure of safety and tolerability [ Time Frame: From first dose of study treatment, until 30 days after the last dose (for each patient) ] [ Designated as safety issue: Yes ]
    Summaries will include rates of occurrence of any AEs, rates of AEs by system organ classification (SOC),rates of discontinuation of study treatment due to AEs.

  • Characterize exposure-response relationships for measures of effectiveness and toxicity [ Time Frame: During the first course of elacytarabine ] [ Designated as safety issue: No ]

Enrollment: 381
Study Start Date: June 2010
Study Completion Date: June 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Elacytarabine
N/A
Drug: Elacytarabine
Elacytarabine 2000 mg/m2/d administered as a continuous intravenous infusion (CIV) in a d 1-5 q3w cycle.
Active Comparator: Investigator's Choice Drug: Investigator's Choice
E.g. cytarabine single agent/combinations, hypomethylating agents, best supportive care (BSC)

Detailed Description:

The study investigates the new nucleoside analogue derivative, elacytarabine, as treatment for patients with relapsed or refractory Acute Myeloid Leukemia (AML). To be included in the study, patients must have failed to respond to two or three different therapies for AML, or have obtained remission but then relapsed within a relatively short period of time. Patients of age ≥ 65 with adverse cytogenetics can be included in the study after having received one and up to three previous induction/re-induction therapies.

Elacytarabine is an investigational drug which is not commercially available. It is the elaidic acid ester derivative of cytarabine. Cytarabine is routinely used in the treatment of patients with AML. A substantial portion of AML patients have a deficient uptake of cytarabine, often explained by lack of a transport protein (hENT1) in the leukemic cell membrane. Due to the elaidic acid (a naturally occurring fatty acid), cellular uptake of elacytarabine is independent of this transport protein.

Patients included in the study will be randomized to elacytarabine or control treatment. Since there is no standard therapy for relapsed or refractory AML, there is a list of 7 control treatments and the investigator has to choose one that is locked before randomization.

Elacytarabine is given as a continuous infusion over five days, followed by a rest period of minimum two weeks. Investigator's choice treatment is given according to the specific routine.

After each course response evaluation and a decision on further treatment will be made.

Repeated courses of elacytarabine and control treatment might be needed to attain and/or maintain complete remission or clinical benefit.

After the end of study treatment, all patients will be followed for relapse and survival.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years of age or older
  • Confirmed diagnosis of AML according to WHO classification (excluding acute promyelocytic leukaemia) who have received two or three previous induction/re-induction regimens or patients of age ≥ 65 with adverse cytogenetics who have received 1-3 previous induction/re-induction regimens. One of the (re-)induction regimens could be stem cell transplantation (SCT) for achievement of remission. Maintenance and consolidation (including SCT) may have been given, but are not counted as previous regimens.
  • Bone marrow aspirates and/or biopsies must contain > 5 % leukaemic blast cells or patient must have biopsy-proven extramedullary AML, or patient's peripheral blood shows occurrence of leukaemic blast cells
  • Patients must

    • have never attained CR or CRi (primary refractory), or
    • have failed initial induction therapy, and have attained CR or CRi after salvage therapy(ies), and then relapsed within < 6 months, or
    • have attained CR or CRi after initial induction therapy and relapsed within <12 months, and failed to respond to salvage therapy(ies), or
    • have relapsed after the latest CR or CRi within < 6 months
  • Patients younger than 65 years should have received previous treatment with cytarabine
  • Patients must have recovered from previous bone marrow and/or stem cell transplantation to a stage that the patient can tolerate the study treatment. There is no restriction on number of regimens or type of treatment administered for maintenance or consolidation during previous stages of the disease
  • ECOG performance status (PS) of 0 - 2
  • Women of child-bearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to treatment start
  • Male and female patients must use acceptable contraceptive methods for the duration of time on study, and males also for 3 months after the last elacytarabine dose
  • Capable of understanding and complying with protocol requirements, and must be able and willing to sign a written informed consent form

Exclusion Criteria:

  • A history of allergic reactions to egg. A history of allergic reactions of CTCAE grade 3 or 4 to cytarabine
  • Persistent clinically significant toxicities from previous chemotherapy
  • A cancer history that, according to the investigator, might confound the assessment of the study endpoints
  • Known positive status for human immunodeficiency virus (HIV)
  • Pregnant and nursing patients
  • Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements
  • Impairment of hepatic or renal function to such an extent that the patient, in the opinion of the investigator, will be exposed to an excessive risk if entered into this clinical study
  • Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure. Any New York Heart Association (NYHA) functional classification grade 3 or 4
  • Applicable only for patients for whom an anthracycline is part of the selected control treatment: Left ventricular ejection fraction (LVEF) must be ≥ 45 % as measured by MUGA scan or 2D ECHO within 14 days prior to start of therapy. Either method is acceptable for measuring LVEF
  • Applicable only for patients for whom an anthracycline is part of the selected control treatment: The patient should tolerate minimum one course of combination therapy
  • Any anti-leukaemic agents within the last 3 weeks. Hydroxyurea,however, is allowed for up to 12 hours prior to study treatment
  • Any investigational treatment within the last 14 days
  • Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01147939

  Show 73 Study Locations
Sponsors and Collaborators
Clavis Pharma
Investigators
Principal Investigator: David Rizzieri, MD Duke University Medical Center, Durham, NC, USA
Study Chair: Francis J Giles, MD, PhD Cancer Therapy & Reseach Center at the University of Texas Health Science Center San Antonio, TX, USA
  More Information

Additional Information:
No publications provided by Clavis Pharma

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Clavis Pharma
ClinicalTrials.gov Identifier: NCT01147939     History of Changes
Other Study ID Numbers: CP4055-306
Study First Received: April 14, 2010
Last Updated: September 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Clavis Pharma:
Acute Myeloid Leukaemia
AML
Haematology
Investigator's Choice
Elacytarabine
Refractory or relapsed AML
Phase III
Randomized
CLAVELA
CP4055-306
Elacyt

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 29, 2014