Neoplasms

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Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

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All Drugs and Chemicals

Cytarabine

Elacytarabine 2000 mg/m2/d administered as a continuous intravenous infusion (CIV) in a d 1-5 q3w cycle.

Elacytarabine

E.g. cytarabine single agent/combinations, hypomethylating agents, best supportive care (BSC)

Investigator's Choice

David Rizzieri, MD

Francis J Giles, MD, PhD

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).

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.

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

A Randomised Phase III Study of Elacytarabine vs. Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia

Time from date of randomisation until the date of death

* 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

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.

Clavis Pharma

Idarubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Elacytarabine 1000 mg/m2/d will be administered as a continuous intravenous infusion (CIV) in a d 1-5 q3w cycle.

Idarubicin will be administered IV at a fixed dose of 12 mg/ m2/d IV on d 1-3 q3w.

It is intended that patients receive remission-induction treatment either as two combination courses, elacytarabine 1000 mg/m2/d + idarubicin 12 mg/m2/d or one combination course, elacytarabine 1000 mg/m2/d + idarubicin 12 mg/m2/d followed by one course elacytarabine 2000 mg/m2/d single therapy.

Elacytarabine plus idarubicin

David A Rizzieri, MD

The main objective of this study is to assess the biological activity of elacytarabine in combination with idarubicin in patients with acute myeloid leukaemia who has failed the first course of a remission-induction treatment with cytarabine (ara-C). In addition, the correlation between hENT1 (human equilibrative nucleoside transporter 1) and overall survival will be studied.

Elacytarabine (CP-4055) is a pro-drug of ara-C currently used in the treatment of patients with acute myeloid leukaemia. Patients with nucleoside transporter deficiency (hENT1) seem to have less benefit from cytarabine compared to those with a high expression of the transporter. Preclinical studies indicate that elacytarabine is independent of this transporter. Therefore, patients with low expression of hENT1 and treated with elacytarabine are anticipated to have a better outcome compared to patients treated with ara-C. The main objective of this study is to assess the biological activity of elacytarabine in combination with idarubicin in patients with acute myeloid leukaemia. In addition, the correlation between hENT1 (human equilibrative nucleoside transporter 1) and overall survival will be studied. Patients will be treated with elacytarabine plus idarubicin independent of their hENT1 status. Determination of the patients' hENT1 expression level will be done retrospectively. This study will also explore the safety profile of elacytarabine in combination with idarubicin.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Elacytarabine Versus Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia (AML)	NCT01147939	Acute Myeloid L...	Elacytarabine Investigator's ...	18 Years -	Clavis Pharma
Study of Elacytarabine Versus Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia (AML)	NCT01147939	Acute Myeloid L...	Elacytarabine Investigator's ...	18 Years -	Clavis Pharma
A Study of Elacytarabine (CP-4055) Plus Idarubicin as Second Course Remission-Induction Therapy in Patients With Acute Myeloid Leukaemia	NCT01035502	Acute Myeloid L...	Elacytarabine p...	18 Years -	Clavis Pharma
Study of Elacytarabine Versus Investigator's Choice in Patients With Late Stage Acute Myeloid Leukaemia (AML)	NCT01147939	Acute Myeloid L...	Elacytarabine Investigator's ...	18 Years -	Clavis Pharma

Spots Global Cancer Trial Database for elacytarabine