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Trial registered on ANZCTR


Registration number
ACTRN12619000556145
Ethics application status
Approved
Date submitted
28/03/2019
Date registered
10/04/2019
Date last updated
13/03/2020
Date data sharing statement initially provided
10/04/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Maintenance treatment with low-dose lenalidomide after allogeneic stem cell transplantation for patients with acute myeloid leukaemia or myelodysplastic syndrome
Scientific title
A Phase I study to assess the safety of micro-dose lenalidomide as maintenance therapy post-allogeneic haematopoietic cell transplantation for patients with acute myeloid leukaemia or myelodysplastic syndromes, at high risk of relapse
Secondary ID [1] 297831 0
Nil
Universal Trial Number (UTN)
Trial acronym
MicroLEN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute myeloid leukaemia
312200 0
Myelodysplastic syndrome 312201 0
Condition category
Condition code
Blood 310745 310745 0 0
Haematological diseases
Cancer 310832 310832 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Phase I dose escalation study of micro-dose oral lenalidomide as maintenance therapy after allogeneic stem cell transplantation for patients with AML or MDS at high risk of relapse.

Participants commence lenalidomide oral tablets from day 40 post-allogeneic transplant, as per the dosing levels described below:
Dose level 1: lenalidomide 2.5mg oral weekly
Dose level 2: lenalidomide 2.5mg oral twice per week
Dose level 3: lenalidomide 5mg oral twice per week
Dose level 4: lenalidomide 5mg oral every second day
Dose level 5: lenalidomide 10mg oral every second day

Treatment will continue for up to 48 weeks unless there is disease progression or unacceptable toxicity. Intervention adherence will not be routinely assessed.
Intervention code [1] 314068 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319594 0
The composite incidence of death, grade 3-4 infection, grade 3-4 acute GVHD, grade 3-4 haematologic and non-haematologic toxicity

Outcome definitions:
Acute GVHD will be assessed according to consensus criteria (Glucksberg criteria)
Grade 3-4 infection, haematologic toxicity and non-haematologic toxicity are defined according to CTCAE v4.0 criteria
Timepoint [1] 319594 0
120 days after initiation of lenalidomide
Secondary outcome [1] 368817 0
Overall survival, defined as the time from transplant to the date of death from any cause
Timepoint [1] 368817 0
1 year post-transplant
Secondary outcome [2] 369098 0
Progression-free survival defined as the time from transplant to leukaemia progression or death, whichever comes first. Leukaemia progression will be defined as the presence of circulating leukaemia blasts, bone marrow blasts greater than 5% of total cellularity or the presence of new extramedullary leukaemia.
Timepoint [2] 369098 0
1 year post-transplant

Eligibility
Key inclusion criteria
Each patient must have one of the following:
a. High risk AML, defined as any of:
• Not in complete remission (CR) at time of alloHSCT
• Adverse risk cytogenetics at any stage of disease
• FLT3-ITD mutation
• Prior induction failure
• Evidence of pre-transplant minimal residual disease either by cytogenetics or by flow cytometry. If flow cytometry is the selected method used, MRD must be greater than 0.1%.
• In second complete remission if duration of first complete remission was less than or equal to 6months.
• Transformation from myeloid neoplasm at any stage

OR

b. High risk MDS, defined as any of:
• Adverse risk cytogenetics at any stage of disease
• Over 10% blasts in blood or marrow aspirate pre-transplant

AND must meet ALL of the following general inclusion criteria:
a. Age 18 years or older.
b. No prior exposure to lenalidomide.
c. Alkaline phosphatase and transaminases less than or equal to 2 x ULN
d. Creatinine clearance greater than or equal to 30 ml/min (calculated by Cockcroft-Gault formula
e. Females of childbearing potential must use an effective method of contraception or practice absolute abstinence for 4 weeks prior to lenalidomide therapy, during treatment and 4 weeks after treatment discontinuation
f. Male patients must use contraception during lenalidomide treatment and for 1 week after completion of treatment
g. ECOG performance status 0-2
h. Life expectancy greater than 6 months
i. Patient’s written informed consent
j. Subjects must agree not to share their medication and return unused supplies
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a. Grade 2-4 aGVHD
b. Relapsed or progressive disease on screening bone marrow biopsy
c. Active second malignancy currently requiring treatment
d. Known hypersensitivity with anaphylactic reaction to lenalidomide
e. Class III or IV cardiac disease defined by the NYHA.
f. Severe or debilitating pulmonary disease.
g. Severe or debilitating central nervous system disease or cerebral dysfunction.
h. Active bacterial, viral or fungal infection
i. Human Immuno-deficiency Virus (HIV) infection.
j. Any coexisting medical or psychological condition that would preclude participation in the required study procedures.
k. Female patients who are both lactating and breast-feeding or have a positive serum pregnancy test during the screening period or a positive pregnancy test on Day 1

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
VIC
Recruitment hospital [1] 13516 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 26135 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 302353 0
Commercial sector/Industry
Name [1] 302353 0
Celgene
Address [1] 302353 0
60 City Road, Southbank, Victoria, 3006
Country [1] 302353 0
Australia
Primary sponsor type
Hospital
Name
Melbourne Health
Address
Royal Melbourne Hospital
Grattan Street
Parkville 3050
Victoria
Country
Australia
Secondary sponsor category [1] 302239 0
None
Name [1] 302239 0
NA
Address [1] 302239 0
NA
Country [1] 302239 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303027 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 303027 0
Royal Melbourne Hospital
Grattan Street, Parkville
Victoria 3050
Ethics committee country [1] 303027 0
Australia
Date submitted for ethics approval [1] 303027 0
Approval date [1] 303027 0
20/01/2016
Ethics approval number [1] 303027 0

Summary
Brief summary
The purpose of this study is to investigate the safety of low-dose lenalidomide treatment after allogeneic stem cell transplantation for patients with acute myeloid leukaemia or myelodysplastic syndromes at high risk of relapse.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above, and have been diagnosed with either high risk acute myeloid leukaemia (AML), OR high risk myelodysplastic syndrome (MDS).

Study details
All participants in this study will undergo treatment with the drug, lenalidomide, which will commence between day 40-45 after allogeneic stem cell transplant. Lenalidomide is an oral tablet, which will be taken for up to 48 weeks. The dose of lenalidomide in the study will commence at 2.5mg once per week, with subsequent groups increasing to 2.5mg twice per week, 5mg twice per week, 5mg every second day, 10mg every second day. Each participant will be assigned to receive one dose level for the entire study.

The safety of lenalidomide treatment will be assessed by the incidence of side effects 120 days after starting the first dose of lenalidomide.

This study will determine the safest dose of lenalidomide after allogeneic transplantation for patients at high risk of relapse.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92218 0
Prof David Ritchie
Address 92218 0
Clinical Haematology
Royal Melbourne Hospital
Grattan Street, Parkville
Victoria 3050
Country 92218 0
Australia
Phone 92218 0
+61 3 93427000
Fax 92218 0
Email 92218 0
david.ritchie@mh.org.au
Contact person for public queries
Name 92219 0
Prof David Ritchie
Address 92219 0
Clinical Haematology
Royal Melbourne Hospital
Grattan Street, Parkville
Victoria 3050
Country 92219 0
Australia
Phone 92219 0
+61 3 93427000
Fax 92219 0
Email 92219 0
david.ritchie@mh.org.au
Contact person for scientific queries
Name 92220 0
Prof David Ritchie
Address 92220 0
Clinical Haematology
Royal Melbourne Hospital
Grattan Street, Parkville
Victoria 3050
Country 92220 0
Australia
Phone 92220 0
+61 3 93427000
Fax 92220 0
Email 92220 0
david.ritchie@mh.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
Individual participant data will remain confidential
What supporting documents are/will be available?
No other documents available
Summary results
No Results