Main info

Identificatie:

HOVON 92 AML

Sponsor:

HOVON

Working group party:

Leukemia

Age:

18-65

Stadium:

1st lijn

Echelon:

Limited Site Selection

Included patients:

148

(of 800)

Active sites:

28

(of 34)

Title:

Randomized study to assess the added value of Laromustine in combination with standard remission-induction chemotherapy in patients aged 18-65 years with previously untreated acute myeloid leukemia (AML) or myelodysplasia (MDS) (RAEB with IPSS ≥ 1.5).

Timeline

News

Flow

Details

Phase:

Prospective randomized Phase II/III study

Monitoring Type:

Not any more

Objectives:

Primary objectives
For part A of the study:

• To determine the feasibility of Laromustine when given at three possible dose levels together with standard induction cycles I and II in patients with AML/ RAEB with IPSS ≥1.5 in a prospective comparison to standard induction cycles I and II without Laromustine

For part B of the study:

• To evaluate the effect of Laromustine at the selected feasible dose level when combined with remission induction chemotherapy cycles I and II as regards clinical outcome (“event-free survival”) in comparison to remission induction cycles I and II with no addition of Laromustine in a phase III study

Secondary objectives
For part A of the study:

• To evaluate the pharmacokinetics of Laromustine in the combination with cytarabineidarubicin remission induction chemotherapy in a selection of patients at different dose levels of Laromustine as well as in a limited number of controls
• To investigate the clinical efficacy of Laromustine in combination with remission induction chemotherapy cycles I and II with regard to complete remission rate at different dose levels of Laromustine

For part B of the study:

• To investigate the clinical efficacy of Laromustine with regard to the complete remission rate, disease free survival (DFS), risk of relapse and overall survival (OS) when combined with remission induction chemotherapy cycles I and II in all patients
• To investigate the clinical efficacy of Laromustine when combined with remission induction chemotherapy cycles I and II in molecularly and cytogenetically distinguishable subsets with regard to the complete remission rate, disease free survival (DFS), risk of relapse and overall survival (OS)
• To investigate the tolerance and toxicity of Laromustine in combination with remission induction chemotherapy cycles I and II
• To evaluate the pharmacokinetics of Laromustine and cytarabine-idarubicine remission induction chemotherapy in a limited number of patients in both treatment arms
• To assess the effect of Laromustine on peripheral CD34 cell numbers for autologous peripheral blood transplantation
• To determine the prognostic value of molecular markers and gene expression profiles of the leukemia assessed at diagnosis
• To evaluate the treatment effects according minimal residual disease (MRD) measurements following therapy by standardized sampling of marrow/blood
• To evaluate the outcome of allogeneic sibling or unrelated donor SCT and autologous SCT in cytogenetically and molecularly defined and prognostic subgroups of patients.

Eligibility

Inclusion Criteria:

• Age 18-65 years, inclusive
• Subjects with
  • a cytopathologically confirmed diagnosis of AML according WHO classification (excluding acute promyelocytic leukaemia) or
  • a diagnosis of refractory anemia with excess of blasts (RAEB) and IPSS score ≥1.5 or
  • patients with therapy-related AML/RAEB or
  • patients with biphenotypic leukemia (Appendices A1 and A2).
• WHO performance status 0, 1 or 2 (see Appendix I)
• Written informed consent

Exclusion Criteria:

• During part A of the study patients with a good risk AML, if already known at randomisation. These patients will be treated outside the study according to the control arm.
• Acute promyelocytic leukaemia
• Previous treatment for AML or RAEB, except hydroxyurea
• Impaired hepatic or renal function as defined by:
  • ALT and/or AST > 3 x Upper Limit of Normal (ULN), or
  • Bilirubin > 3 x ULN, or
  • Serum creatinine> 3 x ULN (after adequate hydration), unless these are most likely caused by AML organ infiltration,
• Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etcetera),
• Cardiac dysfunction as defined by:
  • Myocardial infarction within the last 6 months of study entry, or
  • Reduced left ventricular function with an ejection fraction < 50% as measured by MUGA scan or echocardiogram (another method for measuring cardiac function is acceptable), or
  • Unstable angina, or
  • Unstable cardiac arrhythmias
• Pregnant or lactating females
• Impossibility to stop Disulfiram (Antabuse) and metronidazol (Flagyl) 24 hours prior to study treatment. (Please note that this medication must be stopped 24 hours prior to study treatment.)
• Unwilling or not capable to use effective means of birth control

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals