enalidomide with epigenetic therapy in relapsed or refractory Acute Myeloid Leukaemia (AML)-Phase II

Phase 2

Withdrawn

• Conditions: relapsed and refractory acute myeloid leukaemia; Cancer - Leukaemia - Acute leukaemia

• Registration Number: ACTRN12612000312842
• Lead Sponsor: Australasian Leukaemia and Lymphoma Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-03-20
• Last Update Posted: 2 August 2023

Recruitment & Eligibility

• Status: Withdrawn
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Male or female patients with one of the following diagnoses:
a.AML failing previous therapy who are not eligible for transplant or who failed to be salvaged by standard therapy. Patients may be either primary refractory (failure to achieve greater than or equal to 50% blast reduction to 10-25% marrow blasts) or relapsed (greater than or equal to 50% increase in blasts to greater than or equal to 10% bone marrow blasts) after no more than 3 previous lines of chemotherapy, which may include hypomethylating agents
OR
b.Myelodysplasia (MDS) transformed to AML with greater than or equal to 20% bone marrow blasts after previous treatment, which may include previous treatment with hypomethylating agents
2.Age 18-80 inclusive
3.ECOG (Eastern Co-operative Oncology Group) Performance Status 0-2
4.White Cell Count (WCC)<15 x 10^9/L (hydroxyurea or thioguanine may be used to reduce the WCC prior to study therapy with a washout period of 24hrs)
5.Adequate hepatic function as defined by bilirubin less than or equal to 2 x the upper limit of normal (ULN) and Alanine transaminase (ALT) & aspartate aminotransferase (AST) less than or equal to 3 x ULN
6.Adequate renal function as defined by serum creatinine less than or equal to 1.3 ULN
7.Serum potassium greater than or equal to 3.8 mmol/L and magnesium greater than or equal to 0.85 mmol/L (electrolyte abnormalities can be corrected with supplementation to meet inclusion criteria)
8.All females of childbearing potential (FCBP) must agree to comply with the lenalidomide Pregnancy prevention risk management plan
9.Females must agree to abstain from breastfeeding during study participation and for at least 28 days after study drug discontinuation
10.All male participants must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy
11.Subjects must agree not to donate blood, semen or sperm while on study treatment and for 28 days after treatment discontinuation
12.Provision of written informed consent

Exclusion Criteria

1.History of major non-compliance to medication
2.Post allogeneic-stem cell transplant patients on immunosuppression therapy greater than or equal to 5mg prednisolone/day or equivalent
3.Evidence of central nervous system (CNS) leukaemia
4.Impaired cardiac function or clinically significant cardiac disease as follows:
a.left ventricular ejection fraction (LVEF) <45% as determined by Multi-gated Acquisition (MUGA) scan or echocardiogram (ECHO)
b.Complete left bundle branch block or right bundle branch block + left anterior hemiblock (bifascicular block)
c.Obligate use of a cardiac pacemaker
d.Congenital long QT syndrome or QTc > 480 msec on the screening electrocardiogram (ECG)
e.Clinically significant resting bradycardia (< 50 beats per minute)
f.Angina pectoris or acute myocardial infarction (AMI) less than or equal to 3 months prior to starting study drug
g.Unstable angina, congestive cardiac failure (CCF) or AMI within the last 6 months
5.Patients taking any concurrent medications which have a known risk of prolonging the QTc interval or inducing Torsades de Pointes tachycardia
6.Significant respiratory disease
7.Uncontrolled active infection with known human immunodeficiency virus (HIV) or Hepatitis type B or C infection
8.Currently active gastrointestinal disease (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection), or other disease, that prevents the patient from absorbing or taking oral medication
9.Any other concurrent severe and/or uncontrolled medical conditions (eg. acute or chronic liver disease, infection, pulmonary disease) that in the opinion of the investigator could potentiate unacceptable safety risks or jeopardise compliance with the protocol
10.Previous adverse reaction to the trial drug/s
11.Has any other clinically important abnormalities as determined by the investigator that may interfere with his or her participation in or compliance with the study
12.Female patients who are pregnant
13.Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To investigate the efficacy of two novel treatments (high dose lenalidomide + azacitidine and high dose lenalidomide + romidepsin) compared with a control treatment (high dose lenalidomide alone) in patients with relapsed or refractory AML as measured by the complete remission (CR) rate following two cycles of therapy. Complete remission will be measured by clinical investigations conducted at usual physician appointments.[After all patients have completed two cycles of chemotherapy]