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Trial registered on ANZCTR


Registration number
ACTRN12615000447550
Ethics application status
Approved
Date submitted
27/02/2015
Date registered
8/05/2015
Date last updated
12/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A 2-stage Phase II study of combination pomalidomide and low dose dexamethasone therapy in patients with relapsed myeloma previously treated wtih lenalidomide maintenance post Autologous Stem Cell Transplant (LEOPARD follow-on study)
Scientific title
A 2-stage Phase II study evaluating the safety and efficacy of combination pomalidomide and low dose dexamethasone therapy in patients with relapsed myeloma previously treated wtih lenalidomide maintenance post Autologous Stem Cell Transplant (LEOPARD follow-on study)
Secondary ID [1] 286226 0
PO-CL-MM-PI-003589
Universal Trial Number (UTN)
U1111-1167-4323
Trial acronym
LEOPARD follow on study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
myeloma 294273 0
Condition category
Condition code
Cancer 294595 294595 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pomalidomide will commence at a dose of 4mg orally daily from Days 1 to 21 of a 28 day cycle for the duration of the study, until disease progression or relapse
Dexamethasone will commence at a dose of 40mg weekly on Days 1, 8, 15 and 22 of a 28 day cycle for the duration of the study, until disease progression or relapse.

Adherence to protocol will be monitored via regular cycles visits to the trial centre for medical review and safety bloods and drug accountability in the form of drug return.
Intervention code [1] 291246 0
Treatment: Drugs
Comparator / control treatment
Historical comparator with cohorts on study MM14.
MM14 data collected between Feb 2013 and current active patients, approximately 80 randomised patients.
Induction therapy consists of 4 cycles of Pomalidomide and Dexamethasone and then patients are randomised at Maintenance with either the same treatment again or up to 13 cycles of pomolidomide only.
Doses are Pomolidomide 4mg orally daily D1-21 of a 28 day cycle. Dexamethasone 40mg orally weekly on D1, 8, 15 and 22 of 28 day cycle.
Control group
Historical

Outcomes
Primary outcome [1] 294419 0
To determine the response rates of salvage treatment with pomalidomide and low dose dexamethasone in patients with MM who develop progressive disease whilst on RAP maintenance post-ASCT.
Response rates to be measured using International Myeloma Working Group IMWG criteria. Assessments include serum protein electrophoresis and immunofixation, urine protein eletrophoresis and immunofixation, serum free light chain assay and Bone Marrow Aspirate Trephine.
Timepoint [1] 294419 0
at time of maximal response or progression or relapse
Secondary outcome [1] 313270 0
To document progression free survival and overall survival.
Timepoint [1] 313270 0
at progression or relapse
Secondary outcome [2] 313271 0
To evaluate kinetics of responses and depth of response (best response, time to response), duration of response. (composite secondary outcome)
Timepoint [2] 313271 0
at progession or relapse
Secondary outcome [3] 313272 0
To document the safety and toxicity profile of pomalidomide in patients previously on RAP maintenance.
Possible side effects include haematological toxicites such as neutropenia and thrombocytopenia and non-haemaotogical toxicites such as rash, venous thrombosis/embolism, constipation, hyper or hypo thyroidism, peripheral neuropathy.
Assessed by physical assessment and safety bloods every cycle.
Timepoint [3] 313272 0
duration of study
Secondary outcome [4] 313273 0
To compare overall response rates (ORR – partial response or better, as defined by the International Myeloma Working Group IMWG criteria) and PFS of study patients to those in comparable cohorts of patients in MM14 study receiving pomalidomide dexamethasone as salvage therapy after multiple lines of prior therapies.
Timepoint [4] 313273 0
at progression or relapse

Eligibility
Key inclusion criteria
1. 18+ years of age and be able to give informed consent

2. Confirmed diagnosis of multiple myeloma with progressive disease as per IMWG criteria

3. Patients must have evaluable multiple myeloma with, at least of the following:
- serum M-protein greater than or equal to 5g/L, or
- urine M-protein greater than or equal to 200mg/24 hour, or
- serum free light chain (SFLC) >100mg/L (involved light chain) and an abnormal kappa/lambda ratio (>4:1 or <2:1), or
- for IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin (total IgA) greater than or equal to 7.5g/L

4. Immediate therapy prior to relapse or progressive disease was lenalidomide maintenance as part of the LEOPARD study
- Note: Patients who discontinued LEOPARD study due to reasons other than progression (such as toxicity, consent withdrawal) and have subsequent relapse may be eligible for inclusion

5. Life expectancy of > 16 weeks

6. Patient must be greater than or equal to 7 days from prior focal radiotherapy, and greater than or equal to 2 weeks from last dose of lenalidomide and/or prednisolone, and/or major surgery prior to the first dose of study drug. No other anti-myeloma therapy is given between cessation of RAP maintenance and commencement of Pomalidomide therapy.

7. Adequate organ function and absence of any other absolute contraindications to the use of pomalidomide or dexamethasone

8. ECOG performance status 0-2

9. All women of childbearing potential must agree to have a negative pregnancy test in the 24hrs before commencing pomalidomide, take adequate precautions to prevent pregnancy, and not plan on conceiving children during or within 6 months following pomalidomide

10. All males must use barrier contraception during and for 4 weeks after completing pomalidomide.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
N/A

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 who are eligible and provide consent will be enrolled. All patients will receive the same treamtent.
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
Simons Two Stage design approach.
In stage 1, at least 3 out of 9 patients must achieve an acceptable level of response after 4 cycles of therapy to proceed to Stage 2 where a further 21 patietns are to be recruited.
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Data from all patients who match Study inclusion criteria (but not exclusion criteria) and receive >1 dose of Pomalidomide will be analysed on a modified intention-to-treat basis for safety and efficacy.
The primary outcome variable will be the proportion of patients who respond (PR, VGPR, CR, sCR) to pomalidomide/ dexamethasone salvage therapy. Currently there are 33 active patients on the LEOPARD study. Most of them will eventually develop progressive disease. A sample size of 30 (n=30) is expected.
Simon's two-stage design will be used. An estimated response probability of standard salvage therapy with Thalidomide Dexamethasone of 0.35 and an estimated response probability with study drug Pomalidomide Dexamethasone of 0.60 are used. The null hypothesis that the true response rate is 0.35 will be tested against a one-sided alternative. In the first stage, 9 patients will be accrued. If there are 3 or fewer responses (partial responses or better) in these 9 patients, the study will be stopped. Otherwise, 21 additional patients will be accrued for a total of 30. The null hypothesis will be rejected if 14 or more responses are observed in 30 patients. This design yields a type I error rate of 0.05 and power of 0.8 when the true response rate to pomalidomide is 0.60. The first major analysis of results will take place after all patients have either come off trial (due to death, progression, intolerance or patient choice) or received 12 months of protocol treatment. A further analysis will take place after all patients have had a minimum of 2.5 years follow-up.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
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] 3526 0
The Alfred - Prahran
Recruitment postcode(s) [1] 9289 0
3004 - St Kilda Road Melbourne

Funding & Sponsors
Funding source category [1] 290834 0
Commercial sector/Industry
Name [1] 290834 0
Clegene Pty Ltd
Address [1] 290834 0
Level 7
607 St Kilda Road
Melbourne
3004
Country [1] 290834 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
55 Commercial Road
Melbourne
3004
Country
Australia
Secondary sponsor category [1] 289525 0
Commercial sector/Industry
Name [1] 289525 0
Celgene Pty Ltd
Address [1] 289525 0
Level 7
607 St Kilda Road
Melbourne
3004
Country [1] 289525 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292456 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 292456 0
55 Commercial Road
Melbrourne
3004
Ethics committee country [1] 292456 0
Australia
Date submitted for ethics approval [1] 292456 0
26/06/2014
Approval date [1] 292456 0
26/11/2014
Ethics approval number [1] 292456 0
HREC/14/ALFRED/22

Summary
Brief summary
This study aims to investigate whether ongoing treatment with prednisolone and dexamethasone can supress multiple myeloma as post-autograft maintenance therapy.
Who is it for?
You may be eligible to join this study if you are aged 18 years or above and have received lenalidomide maintenance as part of the LEOPARD study as immediate therapy prior to relapse or progressive disease.
Study details.
All participants in this study will receive a therapy consisting of Pomalidomide and Dexamethasone. Both will be taken orally at a 28 day cycle, Pomalidomide at a dose of 4mg (starting dose) daily from Days 1 to 21, and Dexamethasone at a dose of 40mg (starting dose) weekly on Days 1, 8, 15, 22. Blood tests will be taken every cycle (28 days) to assess safety, tolerability and efficacy of the treatment. A bone marrow biopsy will be performed at the beginning of the study and whole body x-ray will be taken at the beginning and end of the study. Participants will be followed-up until they complete the study to determine response rates, survival and safety and toxicity of the this treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 55170 0
Prof Andrew Spencer
Address 55170 0
Malignant Haematology and Stem Cell transplantation Service
Ground Floor South Block
55 Commercial Road
Melbourne
VIC
3004
Country 55170 0
Australia
Phone 55170 0
+61 3 9076 3451
Fax 55170 0
Email 55170 0
aspencer@netspace.net.au
Contact person for public queries
Name 55171 0
Ms Nola Kennedy
Address 55171 0
Malignant Haematology and Stem Cell transplantation Service
1st Floor South Block
55 Commercial Road
Melbourne
VIC
3004
Country 55171 0
Australia
Phone 55171 0
+61 3 9076 2217
Fax 55171 0
Email 55171 0
n.kennedy@alfred.org.au
Contact person for scientific queries
Name 55172 0
Prof Andrew Spencer
Address 55172 0
Malignant Haematology and Stem Cell transplantation Service
Ground Floor South Block
55 Commercial Road
Melbourne
VIC
3004
Country 55172 0
Australia
Phone 55172 0
+61 3 9076 3451
Fax 55172 0
Email 55172 0
aspencer@netspace.net.au

No information has been provided regarding IPD availability
Summary results
No Results