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Trial registered on ANZCTR


Registration number
ACTRN12612000303842
Ethics application status
Approved
Date submitted
9/03/2012
Date registered
16/03/2012
Date last updated
1/08/2019
Date data sharing statement initially provided
1/08/2019
Date results information initially provided
1/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Lenalidomide with epigenetic therapy in relapsed or refractory Acute Myeloid Leukaemia (AML)-Phase I
Scientific title
A Strategy of High-Dose Lenalidomide in Combination with Epigenetic Therapies for Relapsed or Refractory Acute Myeloid Leukaemia (AML)- Phase I
Secondary ID [1] 280098 0
ALLG AMLM17
Universal Trial Number (UTN)
U1111-1124-3757
Trial acronym
ALLG AMLM17
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed or refractory Acute Myeloid Leukaemia (AML) 286036 0
Condition category
Condition code
Cancer 286225 286225 0 0
Leukaemia - Acute leukaemia
Blood 302969 302969 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Phase I study aims to find the maximum tolerated dose (MTD) of intravenous (i.v) romidespin when delivered in combination with 50mg oral lenalidomide daily on days 8-28. Romidepsin will be delivered on days 1,8 and 15 at either 8, 10, 12 or 14mg/m^2, or on days 1 and 15 at 8mg/m^2. The actual dose administered depends on which dose cohort is currently open- for more information see 'other design features'. Cycles are 6 weeks and are continuous unless toxicity warrants withholding dose. Provided drug is tolerated and a response is seen at 2 cycles, treatment should continue for at least 6-12 cycles, and beyond 12 cycles at the discretion of the study Principal Investigator (PI). A Phase II study follows on from the Phase I but patients enrolled in the Phase I will not participate in the Phase II study. Details for the Phase II study can be found here: https://www.anzctr.org.au/registry/trial_review.aspx?ID=362223
Intervention code [1] 284423 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 286704 0
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
Timepoint [1] 286704 0
55 days following the first dose of treatment for the final accrued evaluable patient
Secondary outcome [1] 296495 0
To determine the preliminary efficacy of high dose lenalidomide in combination with romidepsin using information obtained from clinical investigations
Timepoint [1] 296495 0
following completion of 2 cycles of treatment for all patients
Secondary outcome [2] 296496 0
To investigate quality of life (QOL) during the first two cycles of treatment using an appropriate QOL tool
Timepoint [2] 296496 0
following completion of 2 cycles of treatment for all patients

Eligibility
Key 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
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
n/a
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
n/a
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
If 1/3 patients in a particular dose cohort have a dose limiting toxicity (DLT), the cohort will be expanded to 6 patients. If > 1/3 or 1/6 patients have a DLT, the previous dose will be the MTD. If less than or equal to 1/3 or 1/6 patients have a DLT in a particular dose cohort, the next highest dose cohort will be opened to accrual.
If the initial dose cohort results in > 1/3 or 1/6 patients having a DLT, deescalation of dose cohorts will occur. If, in the descalated dose cohort, less than or equal to 1/3 or 1/6 patients have a DLT, this will be the MTD. If > 1/3 or 1/6 patients have a DLT in the descalated dose cohort, the enxt lowest dose cohort will open to accrual.
The MTD will not be determined from this study if > 1/3 or 1/6 patients have a DLT in the lowest dose cohort, or less than or equal to 1/3 or 1/6 patients have a DLT in the highest dose cohort. In either of these two instances, the linked Phase II study will proceed as a comparison between azacitidine and lenaliomide and lenalidomide only.
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 8302 0
The Alfred - Prahran
Recruitment hospital [2] 8303 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 8304 0
Gosford Hospital - Gosford
Recruitment postcode(s) [1] 16367 0
2250 - Gosford

Funding & Sponsors
Funding source category [1] 284854 0
Other Collaborative groups
Name [1] 284854 0
Australasian Leukaemia and Lymphoma Group
Address [1] 284854 0
Ground Floor, 35, Elizabeth Street
Richmond
VIC 3121
Country [1] 284854 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
Ground Floor, 35, Elizabeth Street
Richmond
VIC 3121
Country
Australia
Secondary sponsor category [1] 283734 0
None
Name [1] 283734 0
Address [1] 283734 0
Country [1] 283734 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286844 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 286844 0
The Alfred
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 286844 0
Australia
Date submitted for ethics approval [1] 286844 0
01/07/2012
Approval date [1] 286844 0
11/11/2013
Ethics approval number [1] 286844 0
118/13

Summary
Brief summary
The outcome in patients with Acute Myeloid Leukaemia (AML) who fail to respond to treatment or relapse after treatment is extremely poor. There is no standard treatment for these patients. This study aims to investigate the appropriate dose of the drug romidepsin (a type of chemotherapy) delivered with high dose lenalidomide (a type of chemotherapy) in the treatment of advanced AML. The study plans to treat up to 18 patients in a number of sites throughout Australia. The primary aim of this initial study is to find a safe dose of romidepsin when delivered with high dose lenalidomide. This initial stage of the study will flow into a larger study comparing 3 different treatments in advanced AML, however if you participate in this Phase I study, you will not then be eligible for the following Phase II study.
Trial details: In this study you will receive the drug romidespin delivered intravenously (i.v) on days 1,8 and 15 of a 6-week treatment cycle at a dose of either 8, 10, 12 or 14mg/m^2, or on days 1 and 15 at 8mg/m^2. The actual dose will depend on what stage of the trial is currently open. At the same time as the romidespin treatment, you will also receive 50mg oral lenalidomide on a daily basis on days 8-28. The strength of the drug and your tolerance of it will be assessed after 2 cycles, and overall, your treatment should continue for at least 6-12 cycles. Beyond this time, the decision as to whether or not your treatment continues will be at the discretion of the study's Principal Investigator (PI).
Who is it for? This study is open to male or female patients aged 18-80 with either a diagnosis of Acute Myeloid Leukaemia (AML) and failing previous therapy, either primary refractory or relapsed after no more than 3 previous lines of chemotherapy OR a diagnosis of Myelodysplasia transformed to AML after previous treatment. The full details of this study’s inclusion and exclusion criteria can be found in the relevant sections within this record.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33129 0
Dr Andrew Wei
Address 33129 0
Alfred Hospital,
Commercial Road
Prahran
Melbourne
Victoria 3004
Country 33129 0
Australia
Phone 33129 0
+61 3 9076 3451
Fax 33129 0
Email 33129 0
a.wei@alfred.org.au
Contact person for public queries
Name 16376 0
Ms Delaine Smith
Address 16376 0
Ground Floor, 35, Elizabeth Street
Richmond
VIC 3121
Country 16376 0
Australia
Phone 16376 0
+61 3 83739701
Fax 16376 0
Email 16376 0
delaine.smith@allg.org.au
Contact person for scientific queries
Name 7304 0
Dr Andrew Wei
Address 7304 0
Alfred Hospital
Commercial Road
Prahran
Melbourne, Victoria, 3004
Country 7304 0
Australia
Phone 7304 0
+61 3 9076 3451
Fax 7304 0
Email 7304 0
a.wei@alfred.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No individual participant data will be publicly available as it is the aggregate data that is under investigation.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary