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Trial registered on ANZCTR


Registration number
ACTRN12613000993796
Ethics application status
Approved
Date submitted
30/08/2013
Date registered
5/09/2013
Date last updated
26/09/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase I/II clinical study of deliverability and efficacy of high dose lenalidomide for the treatment of adult patients with acute lymphoblastic leukaemia
Scientific title
A phase I/II clinical study of deliverability and efficacy of high dose lenalidomide for the treatment of adult patients with acute lymphoblastic leukaemia.
Secondary ID [1] 283110 0
Nil known
Universal Trial Number (UTN)
U1111-1147-3579
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukaemia 289957 0
Condition category
Condition code
Cancer 290328 290328 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial involves the use of the oral capsules lenalidomide. In the induction phase, patients will be treated with lenalidomide 50 mg/day for 28 days, followed 2 weeks later by another cycle at the same dose. In patients with progressive disease after or during first cycle or patients failing to reduce bone marrow blast count to less than 50% of diagnosis, further two cycles with 65mg (and 75 mg/day, if not responding to 65 mg/day) lenalidomide are planned. In patients with rapidly progressive disease, dexamethasone 20 mg/m2 may be administered weekly for 2 weeks, till the patient has received at least one cycle of 75 mg/day dose. Responding patients will receive 25 mg/day lenalidomide 21 days every month till disease progression as maintenance therapy. Patients experiencing serious toxicity or disease progression will be taken off study. For patients developing a toxicity which in investigator’s opinion doesn’t warrant discontinuation of lenalidomide, may be considered for dose de-escalation if the disease is not progressing. Objective evidence for biological activity of the strategy will be assessed using sensitive flow-based assays on bone marrow samples at baseline, at weeks 4 and 10 then 3 monthly of maintenance therapy.
Lenalidomide will be supplied by the clinical trials pharmacy.Drug accountability and monitoring treatment adherence will be managed in part by the practise of returning containers and/or unused stock to the pharmacy. Regular hospital visits and blood test are also required.

If a response rate of >20% obtained or no patient receives at least one cycle of 75 mg/day lenalidomide, to verify the safety and efficacy of the higher doses level, further patients will be enrolled to an expansion phase until a total of 14 patients have been recruited to the entire study.

For patients relapsing after allogeneic HSCT, the following schedule will be followed: Lenalidomide will be dosed at 10mg daily for 21 of 28 days for cycle #1 (28 day cycle) and escalated to 15mg daily for 21 of 28 days for cycle #2 in the absence of treatment emergent aGvHD. Dexamethasone will be given for the first 2 cycles only, at a dose of 40mg weekly in cycle #1 and 20mg weekly in cycle #2. Dose modification will be allowed for lenalidomide (15mg -> 10mg-> 5mg) and dexamethasone (40mg -> 20mg -> 10mg) as per standard criteria.
Dexamethasone will be given as an oral tablet.
Study drugs must be ceased and recommencement is not permitted upon development of graft versus host disease.

This safety study may form the basis of a larger phase 2 co-operative study to determine whether maintenance therapy with lenalidomide improves survival in ALL.
Intervention code [1] 287833 0
Treatment: Drugs
Comparator / control treatment
no comparator/control arm
Control group
Uncontrolled

Outcomes
Primary outcome [1] 290363 0
to assess the impact of higher doses of lenalidomide on bone marrow blast count in patients with ALL
Timepoint [1] 290363 0
bone marrow aspirate:

Induction cycles- week 4 and 10
maintenance cycles- every 3 months
Secondary outcome [1] 304365 0
Safety information including adverse event information, treatment related mortality, laboratory assessments and vital signs
Timepoint [1] 304365 0
this safety infomation is collected for every patient and analysed for the duration of the study, the onging safety and tolerablity of the trial will be assessed at the time point of each 3rd patient complting their treatment
Secondary outcome [2] 304366 0
Efficacy evaluation inlcuding relapse free survival (RFS),
Timepoint [2] 304366 0
assessment for efficacy done after the completion of 2 cycles of induction (initial assessment done after the 1st induction cycle but second cycle administered irrespective of the reponse at that stage) and after the 5th , 9th and 14th patient.
Secondary outcome [3] 304368 0
exploratory studies including lymphocyt4e cell subsets, changes in pro-survial F-kB pathway, changes in gene expression profiling
Timepoint [3] 304368 0
serum assays to be performed at the following time points

induction cycles: day 1, 5,8,12,19,26 and week 4 and 10
maintenance cycles: day 1, 26
Secondary outcome [4] 304387 0
efficacy evaluation including minimal residual disease eradication (MRD)
Timepoint [4] 304387 0
bone marrow biopsy at the end of the induction cycles and then every three months during maintenance cycyles until disease progression or removed from study due to grade 4 toxicity
Secondary outcome [5] 304388 0
overall survivial (OS)
Timepoint [5] 304388 0
to be assessed for up to 12 months in responding patients or until disease progression, unacceptable toxicity, withdrawal of consent
Secondary outcome [6] 304389 0
efficacy evaluation through quality of life questionnaire FACT-Leu v4.
Timepoint [6] 304389 0
to be assessed via Quality of Life Questionnaire at Induction cycles D 8 & 26 and Maintenance cycles Day 1 of each cycle until removal from study.

Eligibility
Key inclusion criteria
1)ALL patients over the age 18 years with relapsed or refractory disease who are unsuitable for further intensive chemotherapy.
2)Provision of written informed consent
3)Life expectancy of greater than 3 months in relation to diseases other then ALL
4)ECOG performance status 0 – 3
5)Electrolyte levels (potassium, calcium (albumin-adjusted), magnesium, phosphorous) within normal limits (WNL) or easily correctable with supplements
6)Adequate hepatic function as defined by bilirubin less than or equal to 2 x the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than of equal to 3 x ULN
7)Adequate renal function, with serum creatinine equal to or less than 1.5 x ULN
8)Patients with no uncontrolled active infection
9) Women of childbearing potential (WCBP) must:
a. Use two forms of contraception simultaneously
b. Have a negative pregnancy test prior to start of study therapy.
c. She must agree to ongoing pregnancy testing during the course of the study at specified intervals.
d. This applies even if the subject practices complete and continued sexual abstinence

Criteria for Women of non-childbearing potential:
A female patient or a female partner of a male patient is considered to have childbearing potential if she is a sexually mature woman who:
i)has not undergone a hysterectomy or bilateral oopherectomy
ii) has not been naturally post menopausal for at least 24 consecutive months, i.e. has had menses at any time in the preceding 24 months. Note: amenorrhoea following cancer therapy does not rule out childbearing potential.

Male subjects must:
a. Agree to use a condom during sexual contact with a WCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and for 28 days after cessation of study therapy.
b. Agree to not donate semen during study drug therapy and for a period after end of study drug therapy

All subjects must:
a. Have an understanding that the study drug could have a potential teratogenic risk.
b. Agree not to share study medication with another person.
c. Agree not to donate blood during treatment with study therapy and for at least 28 days after cessation of study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1)Any serious medical or psychiatric conditions which the investigator feels may interfere with the patient’s ability to give informed consent or participate in the procedures or evaluations of the study
2)History of major non-compliance to medication
3)Evidence of only CNS leukemia in absence of systemic disease
4)Uncontrolled viral infection with known HIV or Hepatitis type B or C
5)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
6)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
7)Female patients who are pregnant or breastfeeding and the lack of adequate contraception in females of childbearing potential, or their partners

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)
All patients receive treatment drug at the standard doses set out in the protocol.
Allocation to a randomised treatment group is not part of the study design, therefore allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The total patient sample size: 9. This is based on Gehan phase II trial design with minimal expected efficacy of 20% for power 0.85
Analysis plan: The data analysis for efficacy; if < 20% response rate (CR +PR) it will be considered a treatment failure and there will be no further expansion of the cohort. Also haematological and non-haematological toxicity will be analysed after every 3rd patient. Further enrolment if no grade IV non haematological toxicity, except for endocrine dysfunction, gastrointestinal disturbance, thrombo-embolic illness and other which in the opinion of the three investigators and Celgene are not life threatening. Further expansion will be based on efficacy (minimal RR 20%); and would recruit 4 more patients 40% RR ( 5 patients for 35% RR, 6 for 30% RR and 7 for 25% RR) in the initial 9 evaluable patients (power 0.85).

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
15/09/2013
Actual
Date of last participant enrolment
Anticipated
2/09/2014
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
9
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1464 0
The Alfred - Prahran
Recruitment postcode(s) [1] 7299 0
3004 - St Kilda Road Melbourne

Funding & Sponsors
Funding source category [1] 287870 0
Self funded/Unfunded
Name [1] 287870 0
Dr Sushrut Patil
Country [1] 287870 0
Australia
Primary sponsor type
Individual
Name
Dr Sushrut Patil
Address
BMT Unit
Ground Floor, South Block
The Alfred
55 Commercial Road
Melbourne 3004
VICTORIA
Country
Australia
Secondary sponsor category [1] 286597 0
None
Name [1] 286597 0
Address [1] 286597 0
Country [1] 286597 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289812 0
The Alfred Health Human Ethics Committee
Ethics committee address [1] 289812 0
Ethics committee country [1] 289812 0
Australia
Date submitted for ethics approval [1] 289812 0
Approval date [1] 289812 0
06/07/2013
Ethics approval number [1] 289812 0
HREC/11/ALFRED/55

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 42538 0
Dr Sushrut Patil
Address 42538 0
BMT Unit
Ground Floor, South Block
The Alfred
55 Commercial Road
Melbourne 3004
VICTORIA
Country 42538 0
Australia
Phone 42538 0
+61 3 9076 2000
Fax 42538 0
+61 3 9076 2298
Email 42538 0
S.patil@alfred.org.au
Contact person for public queries
Name 42539 0
Sushrut Patil
Address 42539 0
BMT Unit
Ground Floor, South Block
The Alfred
55 Commercial Road
Melbourne 3004
VICTORIA
Country 42539 0
Australia
Phone 42539 0
+61 3 9076 2000
Fax 42539 0
+61 3 9076 2298
Email 42539 0
S.patil@alfred.org.au
Contact person for scientific queries
Name 42540 0
Sushrut Patil
Address 42540 0
BMT Unit
Ground Floor, South Block
The Alfred
55 Commercial Road
Melbourne 3004
VICTORIA
Country 42540 0
Australia
Phone 42540 0
+61 3 9076 2000
Fax 42540 0
+61 3 9076 2298
Email 42540 0
S.patil@alfred.org.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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