ANZCTR - Registration

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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]

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

Condition category

Condition code

Cancer

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]

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]

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]

After all patients have completed two cycles of chemotherapy

Secondary outcome [1]

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]

end of cycle 2 for all patients

Secondary outcome [2]

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]

At the end of follow up

Secondary outcome [3]

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]

28 days after the last patient has completed the last dose of study treatment

Secondary outcome [4]

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]

At the end of follow up

Secondary outcome [5]

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]

After all patients complete 2 cycles of treatment

Secondary outcome [6]

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]

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?

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]

New Zealand

State/province [1]

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

Australasian Leukaemia and Lymphoma Group

Address [1]

Level 6, 372 Albert St.
East Melbourne, Vic., 3002.

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Hospital Ethics Committee

Ethics committee address [1]

The Alfred
55 Commercial Rd, Melbourne VIC 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

01/07/2012

Approval date [1]

11/11/2013

Ethics approval number [1]

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

A/Prof Andrew Wei

Address

Alfred Hospital Commercial Road Prahran Melbourne, Victoria, 3004

Country

Australia

Phone

+61 3 90763451

Fax

andrew.wei@monash.edu.au

Contact person for public queries

Name

Delaine Smith

Address

Australasian Leukaemia and Lymphoma Group, Ground Floor, 35 Elizabeth St, Richmond 3121

Country

Australia

Phone

+61 3 8373 9701

Fax

delaine.smith@allg.org.au

Contact person for scientific queries

Name

Andrew Wei

Address

Alfred Hospital
Commercial Road
Prahran
Melbourne, Victoria, 3004

Country

Australia

Phone

+61 3 90763451

Fax

andrew.wei@monash.edu.au

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 info@allg.org.au

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
19813	Study protocol				Available on request

Results publications and other study-related documents

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