Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612000312842
Ethics application status
Approved
Date submitted
16/03/2012
Date registered
20/03/2012
Date last updated
27/07/2023
Date data sharing statement initially provided
17/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Lenalidomide with epigenetic therapy in relapsed or refractory Acute Myeloid Leukaemia (AML)-Phase II
Scientific title
A Strategy of High-Dose Lenalidomide in Combination with Epigenetic Therapies for Relapsed or Refractory Acute Myeloid Leukaemia (AML)- Phase II
Secondary ID [1] 280116 0
ALLG AMLM17
Universal Trial Number (UTN)
Trial acronym
ALLG AMLM17
Linked study record

Health condition
Health condition(s) or problem(s) studied:
relapsed and refractory acute myeloid leukaemia 286099 0
Condition category
Condition code
Cancer 286292 286292 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Phase II follows on from a separate Phase I study that was designed to find the maximum tolerated dose (MTD) of intravenous (i.v) romidespin when delivered in conjunction with oral lenalidomide. The Phase I study can be found here http://www.anzctr.org.au/trial_view.aspx?ID=343451
The Phase II is a randomised study (1:1:1) comparing 50mg oral lenalidomide daily days 1-28 with either 50mg oral lenalidomide daily days 8-28 in combination with 75mg/m^2 subcutaneous (s.c) Azacitidine on days 1-5 and days 8-9; or 50mg oral lenalidomide daily days 8-28 in combination with maximum tolerated dose (MTD) from Phase I i.v romidepsin. Cycles are continuous 6 week cycles.
Intervention code [1] 284448 0
Treatment: Drugs
Comparator / control treatment
The Phase II study will compare romidepsin and high dose lenalidomide with high dose lenalidomide alone (control) or high dose lenalidomide in combination with azacitidine
Control group
Active

Outcomes
Primary outcome [1] 286706 0
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.
Timepoint [1] 286706 0
After all patients have completed two cycles of chemotherapy
Secondary outcome [1] 296489 0
To compare the two novel treatment arms with the control arm in terms of the overall response rate as defined by the achievement of complete response (CR) or partial response (PR) at the end of cycle 2 using information obtained from clinical investigations
Timepoint [1] 296489 0
end of cycle 2 for all patients
Secondary outcome [2] 296569 0
To compare the two novel treatment arms with the control arm in terms of progression-free survival, event-free survival, disease-free survival and overall survival. The outcome will be assessed using results from medical examinations.
Timepoint [2] 296569 0
At the end of follow up
Secondary outcome [3] 296570 0
To investigate the safety and tolerability of the novel treatments of lenalidomide in combination with azacitidine or romidepsin. The outcome will be assessed using results from medical examinations.
Timepoint [3] 296570 0
28 days after the last patient has completed the last dose of study treatment
Secondary outcome [4] 296571 0
To investigate associations between cytogenetic/molecular AML characteristics and response to treatment. The outcome will be assessed using results from medical examinations and laboratory research.
Timepoint [4] 296571 0
At the end of follow up
Secondary outcome [5] 296572 0
To investigate and compare the two novel treatment arms with the control arm in terms of quality of life over the first two cycles of treatment using the specific QOL questionnaire Fact-Leu
Timepoint [5] 296572 0
After all patients complete 2 cycles of treatment
Secondary outcome [6] 296573 0
To identify molecular markers of AML which correlate with benefit from investigational therapy. The outcome will be assessed using results from medical examinations and laboratory research.
Timepoint [6] 296573 0
At the completion of follow up

Eligibility
Key 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
Minimum age
18 Years
Maximum age
80 Years
Sex
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 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The subject will be consented and undergo screening procedures and meet with a clinician. If subject fulfils eligibility criteria, they will be registered and allocated to randomisation arm centrally. This information will then be communicated to the site (hospital)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
random generation 1:1:1
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Participant recruitment difficulties
Safety concerns
Date of first participant enrolment
Anticipated
1/06/2018
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,ACT,QLD,SA,WA,NT,TAS
Recruitment outside Australia
Country [1] 4199 0
New Zealand
State/province [1] 4199 0

Funding & Sponsors
Funding source category [1] 284906 0
Other Collaborative groups
Name [1] 284906 0
Australasian Leukaemia and Lymphoma Group
Country [1] 284906 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
Level 6, 372 Albert St.
East Melbourne, Vic., 3002.
Country
Australia
Secondary sponsor category [1] 283782 0
None
Name [1] 283782 0
Address [1] 283782 0
Country [1] 283782 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286905 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 286905 0
The Alfred
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 286905 0
Australia
Date submitted for ethics approval [1] 286905 0
01/07/2012
Approval date [1] 286905 0
11/11/2013
Ethics approval number [1] 286905 0

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 compare various chemtherapy combinations, comprising romidepsin and high dose lenalidomide, azacitidine and lenalidomide and high dose lnealiodmide alone in the treatment of advanced AML. The study plans to treat 120 patients in a number of sites throughout Australia and New Zealand. This stage of the study follows on from an initial study that aims to find the appropriate dose of romidepsin. The initial study can be found at http://www.anzctr.org.au/trial_view.aspx?ID=343451

Trial details

In this study you will be allocated to receive either: the drug romidespin delivered intravenously (i.v) on days 1 and 15, and possibly 8, of a 6-week treatment cycle with 50mg oral lenalidomide on a daily basis on days 8-28; the drug azacitidine delivered subcutaneously on days 1-5 and 8-9 of a 6-week treatment cycle with 50mg oral lenalidomide on a daily basis on days 8-28; or 50mg oral lenalidomide on a daily basis on days 1-28. Your response to the treatment 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 33901 0
A/Prof Andrew Wei
Address 33901 0
Alfred Hospital Commercial Road Prahran Melbourne, Victoria, 3004
Country 33901 0
Australia
Phone 33901 0
+61 3 90763451
Fax 33901 0
Email 33901 0
[email protected]
Contact person for public queries
Name 17148 0
Ms Delaine Smith
Address 17148 0
Australasian Leukaemia and Lymphoma Group, Ground Floor, 35 Elizabeth St, Richmond 3121
Country 17148 0
Australia
Phone 17148 0
+61 3 8373 9701
Fax 17148 0
Email 17148 0
[email protected]
Contact person for scientific queries
Name 8076 0
A/Prof Andrew Wei
Address 8076 0
Alfred Hospital
Commercial Road
Prahran
Melbourne, Victoria, 3004
Country 8076 0
Australia
Phone 8076 0
+61 3 90763451
Fax 8076 0
Email 8076 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified IPD data for all data collected during the trial
When will data be available (start and end dates)?
Data available 3 months following publication, for an indefinite period
Available to whom?
Data are potentially available to:
• Researchers from not-for-profit organisations
• Commercial organisations
• Other
Based in:
• Any location
Further information:
All data requests will be considered by the primary sponsor on a case by case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted.
Available for what types of analyses?
Any type of analysis
Assessed on a case-by-case basis
How or where can data be obtained?
Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health/). Search for the ACTRN number in the catalogue to find datasets associated with this trial or email enquiries to [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19813Study protocol    Available on request



Results publications and other study-related documents

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