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Trial registered on ANZCTR


Registration number
ACTRN12610000627055
Ethics application status
Approved
Date submitted
14/07/2010
Date registered
2/08/2010
Date last updated
17/07/2023
Date data sharing statement initially provided
1/05/2019
Date results information initially provided
1/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
High-dose lenalidomide maintenance therapy
in adult acute myeloid leukaemia (AML)
Scientific title
A pilot study exploring high-dose
lenalidomide maintenance therapy in adult acute myeloid leukaemia (AML)
Secondary ID [1] 252218 0
None
Universal Trial Number (UTN)
nil
Trial acronym
nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Newly diagnosed acute myeloid leukaemia (except Acute promyelocytic leukaemia (APML)) 257740 0
Condition category
Condition code
Cancer 257914 257914 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Daily oral lenalidomide maintenance therapy for consecutive 28 day cycles. The first two cycles will be 'high dose' lenalidomide (10-50mg depending on which of 5 cohorts is currently accruing patients), and then patients will complete up to 10 additional 28 day cycles of 10mg oral lenalidomide daily.
Cohort 1: 10mg daily for first two cycles; then if approved by Trial Management Committee (TMC) Cohort 2: 25mg daily for first two cycles; then if approved by TMC
Cohort 3: 30mg daily for first two cycles; then if approved by TMC Cohort 4: 40mg daily for first two cycles; then if approved by TMC Cohort 5: 50mg daily for first two cycles
Intervention code [1] 256804 0
Treatment: Drugs
Comparator / control treatment
nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 258775 0
Determination of maximum tolerated dose (MTD) from dose limiting toxicities (DLTs) occurring in the first cycle of lenalidomide maintenance therapy
Timepoint [1] 258775 0
Up to 28 days after the last evaluable patient from each cohort has completed 1 28 day cycles of 'high dose' lenalidomide therapy, the Trial management committee (TMC) will assess whether the next escalated dose cohort can commence accrual. The MTD will be the dose given to the cohort immediately preceding the cohort where the rate of patients exhibiting DLTs in the first cycle of lenalidomide therapy was >45%, when assessed in a minimum of 6 evaluable patients. If the stopping rule is not reached after completion of cohort M5, MTD will not be defined by this study.
Primary outcome [2] 258776 0
Adverse and serious adverse events during all cycles (up to 12 months) of Lenalidomide maintenance therapy as assessed by Common terminology criteria for Avderse Events (CTCAE) version 4 criteria
Timepoint [2] 258776 0
12 months after final patient was accrued to the study.
Secondary outcome [1] 264835 0
Relapse up to 2 years after the end of maintenance therapy
Timepoint [1] 264835 0
After last patient has ben followed for 2 years after the end of maintenance therapy
Secondary outcome [2] 264836 0
Survival up to 2 years after the end of maintenance therapy
Timepoint [2] 264836 0
After last patient has ben followed for 2 years after the end of maintenance therapy
Secondary outcome [3] 264837 0
Functional Assessment of Cancer-Therapy-Leukemia (FACT-Leu) as a measure of quality of life
Timepoint [3] 264837 0
12 months after all patients have commenced maintenance treatment

Eligibility
Key inclusion criteria
Subjects aged 15 - 65 years at screening. Newly diagnosed acute myeloid leukaemia (except APML) with morphology according to the World Health Organisation (WHO) criteria and confirmed by immunophenotyping. This can include de-novo and secondary/therapy related AML. The inclusion of patients with core binding factor AML and the presence of Fms-like tyrosine kinase 3 (FLT3) mutations will be allowable if patients are not enrolled for other studies targeting these disease groups. Has provided written, informed consent. Life expectancy greater than 3 months. Has registered prior to induction therapy and provided samples at registration for tissue bank and
laboratory studies and during induction and consolidation therapy for correlative studies. Subjects should have completed recommended induction and consolidation therapy as outlined in protocol. If subjects have had dose modifications, eligibility should be discussed with the Principal Investigator. Patients must have achieved complete remission (CR), complete remission with incomplete platelet recovery (CRp) or complete remission with incomplete count recovery (CRi) after one or two rounds of induction chemotherapy before progressing to consolidation chemotherapy. Patients must be in CR or CRp after consolidation chemotherapy. Lenalidomide therapy must be able to commence within 6-16 weeks since completion of the last dose of consolidation chemotherapy. No clinical evidence of deep vein thrombosis. An Eastern Co-operative Oncology Group (ECOG) performance status score of 2 or less at screening. Adequate baseline bone marrow reserve (neutrophils >1.0 x 10^9/L and platelets >75 x 10^9/L) immediately prior to treatment. Adequate cardiac function. Adequate renal and hepatic functions at screening as defined by:a. bilirubin less than or equal to 2 x upper limit of normal (ULN) b. serum creatinine less than or equal to 1.5 x ULN c. Alanine aminotransferase (ALT) less than or equal to 3 x ULN. Ability to comply with the contraceptive and other requirements of the Lenalidomide Risk Management Plan. Subjects must agree not to share their medication and return unused supplies
Minimum age
15 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
History of major non-compliance to medication. Evidence of known central nervous system (CNS) leukaemia. Currently active gastrointestinal disease (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection), or other disease, that, in the nvestigator’s
opinion, prevents the patient from absorbing or taking oral medication. Any other concurrent severe and/or uncontrolled medical conditions (eg. acute or chronic liver disease, infection, pulmonary disease) or clinical abnormalities that in the opinion of the investigator could
potentiate unacceptable safety risks or jeopardise compliance with the protocol. Significant cardiac or respiratory disease. Prior diagnosis of cancer that was either: a. more than 5 years prior to current diagnosis with subsequent evidence of disease recurrence or clinical expectation of recurrence is greater than 10% OR b. within 5 years of current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma or carcinoma in situ of the cervix. Previous adverse reaction to the trial drug/s. Women who are pregnant or lactating. Planned Haemopoietic stem cell transplant (HSCT) within 3 months of commencing maintenance lenalidomide. Delay between day 28 of final induction cycle and day 1 of first cycle of consolidation therapy was greater than 8 weeks. Granulocyte colony stimulating factor (GCSF) within 7 days of commencing lenalidomide treatment. Uncontrolled viral infection with Human Immunodeficiency Virus (HIV) or Hepatitis type B or C.

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)
Patients must be registered centrally prior to commencing induction and consolidation chemotherapy. At completion of consolidation therapy, eligible patients will be enrolled into the maintenance phase. Prior to commencing Screening for maintenance, the central coordinating centre should be contacted to determine that a place in the currently accruing cohort is available.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
nil
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
nil
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2010
Actual
23/08/2011
Date of last participant enrolment
Anticipated
Actual
15/05/2015
Date of last data collection
Anticipated
14/04/2019
Actual
17/04/2018
Sample size
Target
50
Accrual to date
Final
45
Recruitment in Australia
Recruitment state(s)
NSW,VIC,ACT,QLD,SA,WA,NT,TAS
Recruitment postcode(s) [1] 3038 0
2145
Recruitment postcode(s) [2] 3037 0
3002
Recruitment postcode(s) [3] 3036 0
3004
Recruitment postcode(s) [4] 3040 0
3052
Recruitment postcode(s) [5] 3039 0
4102
Recruitment outside Australia
Country [1] 2762 0
New Zealand
State/province [1] 2762 0

Funding & Sponsors
Funding source category [1] 257283 0
Other Collaborative groups
Name [1] 257283 0
Australasian Leukaemia and Lymphoma Group (ALLG)
Country [1] 257283 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group (ALLG)
Address
Level 2, 10 St Andrews Place East Melbourne 3002 Victoria
Country
Australia
Secondary sponsor category [1] 256528 0
None
Name [1] 256528 0
Address [1] 256528 0
Country [1] 256528 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259308 0
The Alfred Research and Ethics Unit
Ethics committee address [1] 259308 0
OFFICE OF ETHICS & RESEARCH GOVERNANCE
Alfred Hospital
Commercial Rd, Prahran, Victoria, 3004
Ethics committee country [1] 259308 0
Australia
Date submitted for ethics approval [1] 259308 0
01/08/2011
Approval date [1] 259308 0
01/08/2011
Ethics approval number [1] 259308 0
Ethics committee name [2] 297717 0
Hunter New England Human Research Ethics Committee
Ethics committee address [2] 297717 0
Locked Bag No 1, New Lambton, NSW, 2305
Ethics committee country [2] 297717 0
Australia
Date submitted for ethics approval [2] 297717 0
06/04/2011
Approval date [2] 297717 0
18/05/2011
Ethics approval number [2] 297717 0
11/05/18/3.01
Ethics committee name [3] 297718 0
Metro South Human Research Ethics Committee
Ethics committee address [3] 297718 0
PAH Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [3] 297718 0
Australia
Date submitted for ethics approval [3] 297718 0
Approval date [3] 297718 0
03/07/2012
Ethics approval number [3] 297718 0
HREC/12/QPAH/76
Ethics committee name [4] 297719 0
Human Research Ethics Committee (TQEH/LMH/MH)
Ethics committee address [4] 297719 0
The Queen Elizabeth Hospital
28 Woodville Rd
Woodville South SA 5011
Ethics committee country [4] 297719 0
Australia
Date submitted for ethics approval [4] 297719 0
Approval date [4] 297719 0
26/08/2011
Ethics approval number [4] 297719 0
2011047
Ethics committee name [5] 297720 0
Central Adelaide Local Health Network Research Ethics Committee
Ethics committee address [5] 297720 0
Royal Adelaide Hospital
North Terrace
Adelaide, SA, 5000
Ethics committee country [5] 297720 0
Australia
Date submitted for ethics approval [5] 297720 0
Approval date [5] 297720 0
14/02/2012
Ethics approval number [5] 297720 0
111033
Ethics committee name [6] 297721 0
Sir Charles Gairdner Hospital HREC
Ethics committee address [6] 297721 0
Level 2 A Block,
Hospital Ave, Nedlands, WA 6009
Ethics committee country [6] 297721 0
Australia
Date submitted for ethics approval [6] 297721 0
Approval date [6] 297721 0
05/10/2011
Ethics approval number [6] 297721 0
2011-077

Summary
Brief summary
Lenalidomide has a variety of reported mechanisms in blood malignancy, including activation of immune cells and anti-proliferative effects on tumor cells and modulation of the bone marrow microenvironment. Currently approved doses of lenalidomide use up to 25 mg for 21 days out of 28. A
recent pilot study in older AML patients used higher and continuous doses of lenalidomide (50mg lenalidomide for 28 days x 2 cycles followed by 10 mg daily for 12 months). This resulted in a 30% complete response rate. This schedule was well tolerated in an elderly AML population. Therefore, lenalidomide at higher doses has substantial activity in AML and deserves further exploration.
To explore the potential clinical value of lenalidomide in prolonging remission in adult AML after chemotherapy, this multicentre Investigator Initiated Australasian study will first investigate the safety and tolerability of increasing doses of lenalidomide (10-50mg per day for 28 days for 2 months) followed by 10mg per day for 10 months.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31392 0
Address 31392 0
Country 31392 0
Phone 31392 0
Fax 31392 0
Email 31392 0
Contact person for public queries
Name 14639 0
Delaine Smith
Address 14639 0
ALLG Level 2, 10 St Andrews Place East Melbourne 3002 Victoria
Country 14639 0
Australia
Phone 14639 0
610396563656
Fax 14639 0
Email 14639 0
delaine.smith@petermac.org
Contact person for scientific queries
Name 5567 0
Andrew Wei
Address 5567 0
Alfred Hospital
Commercial Road
Prahran
Melbourne, Victoria, 3004
Country 5567 0
Australia
Phone 5567 0
+61 3 9076 3451
Fax 5567 0
Email 5567 0
a.wei@alfred.org.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.TypeCitationLinkEmailOther DetailsAttachment
19715Study protocol  info@allg.org.au Access can be requested via the Health Data Austra... [More Details]



Results publications and other study-related documents

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