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Trial registered on ANZCTR


Registration number
ACTRN12615001169538
Ethics application status
Approved
Date submitted
22/10/2015
Date registered
2/11/2015
Date last updated
1/02/2019
Date data sharing statement initially provided
1/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase Ib study of lenalidomide in combination with imatinib for adult patients with chronic myeloid leukaemia in second molecular remission
Scientific title
A Phase Ib study of lenalidomide in combination with imatinib for adult patients with chronic myeloid leukaemia in second molecular remission
Secondary ID [1] 287625 0
RV-CL-CML-PI-005514
Universal Trial Number (UTN)
Trial acronym
LENI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukaemia (CML) 296437 0
Condition category
Condition code
Cancer 296700 296700 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Screening:
Patient will be asked about medical history, including medications, and will undergo a physical examination, including measurement of height, weight, blood pressure, heart rate and temperature. About 33 mL of blood will be collected to assess the levels of BCR-ABL, imatinib, different types of blood cells, blood minerals, and to assess liver and kidney function. Female patients of child bearing potential will also require a pregnancy test (5mL of blood). If 'entry criteria' are met the patient will be able to participate in the study.

Combination Phase:
Patient will take a daily oral dose of lenalidomide in addition to continuing imatinib at the previous stable dose for 6 months. The starting dose of lenalidomide oral capsule will be 5 mg daily for the first 28 day cycle, escalating up to 10 mg daily according to tolerability.
Patient will return to the Study Doctor’s clinic every week for the first month, and every month for the next 5 months for physical examination and measurement of blood pressure, heart rate and temperature. 12 mL (2 and a half teaspoons) of blood will be taken weekly for the first month and monthly thereafter to assess the levels of different types of blood cells, blood minerals, and to assess liver and kidney function. 27 mL (2 tablespoons) of blood will be collected every 2 months for BCR-ABL PCR. After the first 4 weeks and 8 weeks of treatment an additional 5 mL (1 teaspoon) of blood will be collected to measure the amount of imatinib. For female patients of child bearing potential, a further 5 mL (1 teaspoon) of blood will be collected every month for a pregnancy test. A bone marrow is required at the end of the combination phase. Patients will be required to return empty lenalidomide containers to pharmacy. Patients will be asked at each visit whether they have missed any scheduled imatinib doses.

Monotherapy Phase:
The patient will stop taking imatinib, and continue on lenalidomide monotherapy at a dose of up to 10 mg per day orally for up to 6 months, or until molecular recurrence, should this occur sooner..
Patient will return to the Study Doctor’s clinic every month for blood tests. About 40 mL (2 tablespoons) of blood will be taken to assess the levels of BCR-ABL, different types of blood cells, blood minerals, and to assess liver and kidney function. For female patients of child bearing potential, a further 5 mL (1 teaspoon) of blood will be collected every month for a pregnancy test. A bone marrow is additionally required at the end of the Monotherapy Phase. Patients will be required to return empty lenalidomide containers to pharmacy.

Monitoring Phase:
Patient will stop lenalidomide and remain off imatinib. The Monitoring Phase will last for up to 30 months (2 and a half years) unless relapse occurs as decided by clinical discretion of the treating physician..
Patient will continue to have monthly BCR-ABL levels in which 27 mL (2 tablespoons) of blood will be collected for the first 6 months and then every 2 months for the subsequent 18 months, and every 3 months for one year. 4-12 mL (1-2 and a half teaspoons) of blood will be taken 3 monthly for the first 2 years and then yearly for the subsequent year to assess the levels of different types of blood cells, important blood minerals, and to assess liver and kidney function. A bone marrow is additionally required at month 3 of the Monitoring Phase.

Re-Treatment Phase:
Patients who relapse at any time after stopping imatinib will stop taking lenalidomide (if applicable) and resume imatinib at the previous effective and tolerated dose for as long as is needed. During the Re-Treatment Phase the response to treatment will be monitored every month for at least 6 months. If any patient shows a poor response to re-treatment with imatinib, then alternative treatment will be offered.

Follow-Up Phase:
The Follow-Up Phase will last for 3 years after the completion of the Monitoring or Re-Treatment Phase (if this is needed).
Patient will have blood tests every 6 months for BCR-ABL PCR (27 mL or 2 tablespoons) and yearly to assess the levels of different types of blood cells (4 mL or 1 teaspoon). This will continue for the next 3 years. The total duration for the study will be up to 6 and a half years.
Intervention code [1] 293027 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 296311 0
The primary objective of this study is to assess the safety and tolerability of the combination of imatinib and lenalidomide therapy in CML patients previously on imatinib therapy for at least 12 months. Safety assessments in the Combination Phase will consist of monitoring and recording all adverse events and their relationship to the combination of imatinib and lenalidomide. Plasma imatinib drug levels will be measured before and after the addition of lenalidomide to determine whether lenalidomide alters imatinib levels. During the Monotherapy Phase and until 28 days after the last dose of lenalidomide all adverse events will be reported, with an assessment of their relationship to lenalidomide treatment. Significant past medical history and current medical conditions will be recorded at the screening visit prior to the start of the study, and significant findings made during the study which meet the definition of an adverse event will be reported. Safety assessments will include the regular monitoring of haematology and blood chemistry, physical examination, and information about other medication and therapies.
Timepoint [1] 296311 0
Weekly assessments for the first month of Combination Phase, then monthly assessment until 28 days after last dose of Monotherapy Phase.
Secondary outcome [1] 318139 0
1. To assess the proportion of patients who remain in stable major molecular response (MMR) 2 years after ceasing imatinib, assessed by serum RQ-PCR assay for BCR-ABL.
Timepoint [1] 318139 0
2 years after ceasing imatinib
Secondary outcome [2] 318140 0
2. To assess the proportion of patients who have stable undetectable minimal residual disease (UMRD) 2 years after ceasing imatinib, assessed by serum RQ-PCR assay for BCR-ABL.
Timepoint [2] 318140 0
2 years after ceasing imatinib
Secondary outcome [3] 318141 0
3. To assess the proportion of patients who regain MMR within 6 months after restarting imatinib treatment for a second molecular recurrence, assessed by serum RQ-PCR assay for BCR-ABL.
Timepoint [3] 318141 0
6 months after restarting imatinib treatment for a second molecular recurrence

Eligibility
Key inclusion criteria
1. Diagnosis of chronic myeloid leukaemia associated with BCR-ABL quantifiable by RQ-PCR at the time of commencing imatinib therapy.

2. Patient experienced molecular recurrence of BCR-ABL during a previous medically supervised period of imatinib withdrawal, resulting in resumption of imatinib treatment, and:
a. MR4.5 at the time of having previously stopped imatinib.
b. No more than two BCR-ABL results above 0.01% in the two year period prior to having stopped imatinib.
c. Willing and able to provide all BCR-ABL RQ-PCR results from the two year period prior to having stopped imatinib, and for the period up to the time of restarting imatinib treatment.

3. Patient regained MR4.5 after restarting imatinib treatment (as detailed in criterion 3) and has maintained MR4.5 on at least 2 tests in the 12 months prior to screening, and:
a. No BCR-ABL result above 0.1% (MMR) in the 12 month period prior to screening.
b. No more than one BCR-ABL result above 0.01% in the 12 month period prior to screening.
c. Willing and able to provide copies of all BCR-ABL RQ-PCR test results from the 12 month period prior to screening.

4. Currently taking imatinib and no other current or planned anti-leukaemia therapies.

5. MR4.5 confirmed at screening.

6. No signs of extramedullary leukaemia.

7. ECOG performance status 0, 1, or 2.

8. Calculated (Cockcroft-Gault) or measured glomerular filtration rate greater than or equal to 30 mL/min

9. Female patients must have a negative pregnancy test within 24 hours before commencing lenalidomide OR have been amenorrhoeic for at least two years. All patients of reproductive potential must agree to birth control for the duration of the study.

10. Life expectancy of more than 12 months in the absence of any intervention.

11. Patient has given written, informed consent to participate in the study (which includes consent to obtain samples for the correlative studies).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient has received another investigational agent for treatment of CML within last 12 months.

2. Atypical BCR-ABL transcript not quantifiable by standard RQ-PCR.

3. Another primary malignant disease, except those which do not currently require treatment (adequately treated conditions, such as excised non-melanoma skin cancer or cervical intra-epithelial neoplasia would not be considered exclusion criteria. If in doubt, please refer to the Principal Investigator).

4. Another severe and/or life-threatening medical disease.

5. Active liver disease (e.g., chronic active hepatitis, cirrhosis).

6. History of deep venous thrombosis (in the case of clearly provoked thrombosis more than 2 years prior, please refer to the Principal Investigator).

7. Known diagnosis of human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

8. History of non-compliance or inability to grant informed consent.

9. Prior allogeneic stem cell transplantation.

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
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Safety concerns
Date of first participant enrolment
Anticipated
22/03/2016
Actual
22/03/2016
Date of last participant enrolment
Anticipated
15/10/2017
Actual
30/08/2016
Date of last data collection
Anticipated
31/12/2021
Actual
Sample size
Target
20
Accrual to date
Final
3
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 4437 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 10646 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 292187 0
Commercial sector/Industry
Name [1] 292187 0
Celgene Pty Ltd
Country [1] 292187 0
Australia
Primary sponsor type
Other Collaborative groups
Name
South Australian Health & Medical Research Institute (SAHMRI)
Address
North Terrace
Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 290865 0
None
Name [1] 290865 0
Address [1] 290865 0
Country [1] 290865 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293662 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 293662 0
Ethics committee country [1] 293662 0
Australia
Date submitted for ethics approval [1] 293662 0
06/07/2015
Approval date [1] 293662 0
11/09/2015
Ethics approval number [1] 293662 0
150711

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

Contacts
Principal investigator
Name 60858 0
Dr David Ross
Address 60858 0
SA Pathology, Frome Road, Adelaide, SA 5000
Country 60858 0
Australia
Phone 60858 0
+61 8 8222 3228
Fax 60858 0
Email 60858 0
david.ross@health.sa.gov.au
Contact person for public queries
Name 60859 0
David Ross
Address 60859 0
SA Pathology, Frome Road, Adelaide, SA 5000
Country 60859 0
Australia
Phone 60859 0
+61 8 8222 3228
Fax 60859 0
Email 60859 0
david.ross@health.sa.gov.au
Contact person for scientific queries
Name 60860 0
David Ross
Address 60860 0
SA Pathology, Frome Road, Adelaide, SA 5000
Country 60860 0
Australia
Phone 60860 0
+61 8 8222 3228
Fax 60860 0
Email 60860 0
david.ross@health.sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
there is currently no plan to share individual participant data (IPD) for this trial


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseImmune effector recovery in chronic myeloid leukemia and treatment-free remission.2017https://dx.doi.org/10.3389/fimmu.2017.00469
N.B. These documents automatically identified may not have been verified by the study sponsor.