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

Phase 1

Completed

Conditions: Relapsed or refractory Acute Myeloid Leukaemia (AML)
Cancer - Leukaemia - Acute leukaemia
Blood - Haematological diseases

Registration Number: ACTRN12612000303842

Lead Sponsor: Australasian Leukaemia and Lymphoma Group

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 20

Inclusion Criteria

1.Male or female patients with one of the following diagnoses:
a. AML failing previous therapy, 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 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 Performance Status 0-2

4.White Cell Count <15 x 10^9/L

5.Adequate hepatic function as defined by bilirubin less than or equal to 2 x the upper limit of normal (ULN) and Aspartate transaminase & Alanine transaminase 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

8.Females of childbearing potential must use effective methods of contraception or practice absolute abstinence for 4 weeks prior to lenalidomide therapy, during treatment and 4 weeks after treatment discontinuation

9.Male patients must use contraception during lenalidomide treatment and for 4 weeks after discontinuation of treatment

10.Subjects must agree not to donate blood, semen or sperm while on lenalidomide and for 4 weeks after treatment discontinuation

11.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 Ventricle 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 bpm)
f.Angina pectoris or acute myocardial infarction (AMI) greater 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.Clinically significant respiratory disease
7.Uncontrolled active infection with known HIV or Hepatitis type B or C infection
8.Currently active gastrointestinal disease or other disease, that prevents the patient from absorbing or taking oral medication
9.Any other concurrent severe and/or uncontrolled medical conditions 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.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 or breastfeeding and the lack of adequate contraception
13.Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine the maximum tolerated dose of romidepsin when used in combination with lenalidomide for the treatment of patients with relapsed or refractory AML using information obtained from clinical investigations[55 days following the first dose of treatment for the final accrued evaluable patient]

Secondary Outcome Measures

Name	Time	Method
To determine the preliminary efficacy of high dose lenalidomide in combination with romidepsin using information obtained from clinical investigations[following completion of 2 cycles of treatment for all patients];To investigate quality of life (QOL) during the first two cycles of treatment using an appropriate QOL tool[following completion of 2 cycles of treatment for all patients]

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