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Trial registered on ANZCTR


Registration number
ACTRN12612000338864
Ethics application status
Approved
Date submitted
20/03/2012
Date registered
23/03/2012
Date last updated
7/08/2019
Date data sharing statement initially provided
7/08/2019
Date results information initially provided
7/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A prospective randomised Phase II study of single agent pomalidomide maintenance versus combination pomalidomide and low dose dexamethasone maintenance following induction with the combination of pomalidomide and low dose dexamethasone in patients with relapsed and refractory myeloma previously treated with lenalidomide
Scientific title
The effect of Pomalidomide compared to pomalidomide and dexamethasone on natural killer cells and disease response in Relapsed and Refractory Myeloma patients
Secondary ID [1] 280163 0
ALLG MM14
Universal Trial Number (UTN)
U1111-1126-2829
Trial acronym
MM14
Linked study record

Health condition
Health condition(s) or problem(s) studied:
relapsed and refractory multiple myeloma 286088 0
Condition category
Condition code
Cancer 286282 286282 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients will receive 4mg oral pomalidomide daily on a cyclic 21-day out of 28-day schedule with 40mg oral dexamethasone on days 1, 8, 15, & 22 of 28 day cycle for 4 cycles as induction therapy. Patients randomised to the pomalidomide arm for maintenance treatment will receive 4mg oral pomalidomide daily on a cyclic 21-day out of 28-day schedule for approximately 12 cycles. Actual cycle number to be determined by treating clinician and based on response to and tolerability of treatment
Intervention code [1] 284490 0
Treatment: Drugs
Comparator / control treatment
Patients randomised to the control arm for maintenance treatment will receive 4mg oral pomalidomide daily on a cyclic 21-day out of 28-day schedule with 40mg oral dexamethasone on days 1, 8, 15, & 22 of 28 day cycle for approximately 12 cycles. Actual cycle number to be determined by treating clinician and based on response to and tolerability of treatment
Control group
Active

Outcomes
Primary outcome [1] 286750 0
Natural killer (NK) cell quantification (an increase in 30% of NK cell numbers in pomalidomide arm compared to pomalidomide-dexamethasone): assessed by flow cytometry of CD3-CD56+CD16+ Peripheral Blood Mononuclear Cells (PBMC) that were collected at start of induction and at maintenance cycle 6.
Timepoint [1] 286750 0
at start of induction and at maintenance cycle 6
Primary outcome [2] 286751 0
NK cell function (an increase of NK-cell lysis by 30% in the pomalidomide arm compared to pomalidomide-dexamethasone): assessed via lysis of 51Chromium-labelled K562, and myeloma cell lines (eg U266) in vitro at different effector: target ratios using patients' PBMC that were collected at start of induction and at maintenance cycle 6.
Timepoint [2] 286751 0
at start of induction and at maintenance cycle 6
Secondary outcome [1] 296585 0
To evaluate kinetics of responses and loss of response (time to response, time to disease progression) as assessed by clinical investigations after induction, and then after randomisation at maintenance phase.
Timepoint [1] 296585 0
after induction, and after randomisation at maintenance phase.
Secondary outcome [2] 296586 0
To compare Progrssion Free Survival (PFS) between the group of patients receiving single agent Pomalidomide versus the group receiving Pomalidomide-Dexamethasone combination in maintenance therapy.
Timepoint [2] 296586 0
measured from the date of registration (all patients) and from the date of randomisation (randomized patients) until the earliest of the date of relapse, progression or death from any cause
Secondary outcome [3] 296587 0
To document overall survival (OS)
Timepoint [3] 296587 0
measured from the date of registration (all patients) and from the date of randomisation (randomized patients) until the date of death from any cause
Secondary outcome [4] 296588 0
To document the safety/toxicity profile through tabulation of adverse events detected through routine clinical visits of single agent Pomalidomide versus combination Pomalidomide-Dexamethasone maintenance therapy. Adverse events will require clinical interpretation and are detailed in the 'Known and possible side effect(s)' field in the cancer-specific section at the end of this record
Timepoint [4] 296588 0
at the end of trial
Secondary outcome [5] 296589 0
NK cell quantification assessed by flow cytometry of CD3-CD56+CD16+ PBMC that were collected at start of induction and at maintenance cycles 1, 3 and 10.
Timepoint [5] 296589 0
start of induction and at maintenance cycles 1, 3 and 10.
Secondary outcome [6] 296590 0
NK cell function assessed via lysis of 51Cr-labelled K562, and myeloma cell lines (eg U266) in vitro at different effector: target ratios using patients' PBMC that were collected at start of induction and at maintenance cycles 1, 3 and 10.
Timepoint [6] 296590 0
start of induction and at maintenance cycles 1, 3 and 10.

Eligibility
Key inclusion criteria
At study entry:
Diagnosed with relapsed and refractory mutiple myeloma (MM) (diagnosis of MM as per International Myeloma Working Group (IMWG))
-Measurable M-component (monoclonal protein) in serum or urine,
-In patients with no detectable M-component, an abnormal Free light chain (FLC) ratio on the serum FLC assay
At least 2 prior therapies:
-Must include lenalidomide – failing to respond, disease progression during treatment or within 60 days of treatment completion (at least 2 cycles)
-May include autologous stem cell transplant (ASCT) (induction/ASCT/maintenance is one line of therapy).
Eastern Co-operative Oncology Group (ECOG) performance status 0-2
Adequate liver and kidney function (less than or equal to 2 x institutional upper limit of normal)
Haemoglobin (Hb) greater than or equal to 80g/L, Platelet count greater than or equal to 75 x 10^9, absolute neutrophil count greater than or equal to 1.0 x 10^9. Subjects who fail screening due to neutropenia or anaemia will not be permitted to use growth factors to become eligible.
No contraindication to the use of any of the study drugs
No concomitant steroids other than dexamethasone outlined in this protocol
Patient has voluntarily agreed and has given written informed consent.
Life expectancy of > 8 weeks
Patient must be greater than or equal to 4 weeks from prior chemotherapy, radiotherapy, biological therapy, immunotherapy, major surgery or any other investigational anti-cancer therapy prior to the first dose of study drug
Patients to comply with lenalidomide Pregnancy Prevention Plan
Study site must be able to get correlative samples to the Alfred Hospital, Melbourne, within 24 hours of collection.

Prior to randomisation:
Have completed 4 cycles of induction therapy
Have no evidence of progressive MM
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
At both registration and randomisation:
Patients with monoclonal gammopathy of uncertain significance.
Primary amyloidosis
Patients who have received prior allogeneic transplantation < 12 months prior to entering study
Patients who have had prior allogeneic transplantation and show evidence of active graft-versus-host disease that requires immunosuppressive therapy
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or lactating women.
Known Hepatitis B, Hepatitis C, Human immunodeficiency virus (HIV) infection, other immunosuppressive therapy or autoimmune disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients undergo screening during hospital visit after informed consent is obtained. If eligible, patient will be registered centrally, undergo induction treatment, and then if suitable response is obtained, patient is randomised to maintenance treatment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
randomised sequence generated by computer
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
All patients will complete a common induction treatment of -Pomalidomide (4mg orally daily on a cyclic 21-day out of 28 day schedule) and low dose dexamethasone (40mg orally on days 1, 8, 15, & 22 of 28 day cycle) prior to randomisation.
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/09/2012
Actual
25/02/2013
Date of last participant enrolment
Anticipated
Actual
8/10/2015
Date of last data collection
Anticipated
8/10/2018
Actual
8/10/2018
Sample size
Target
80
Accrual to date
Final
82
Recruitment in Australia
Recruitment state(s)
NSW,VIC,ACT,QLD,SA,WA,NT,TAS
Recruitment hospital [1] 8291 0
The Alfred - Prahran
Recruitment hospital [2] 8292 0
Box Hill Hospital - Box Hill
Recruitment hospital [3] 8293 0
The Canberra Hospital - Garran
Recruitment hospital [4] 8294 0
Concord Private Hospital - Concord
Recruitment hospital [5] 8295 0
Concord Repatriation Hospital - Concord
Recruitment hospital [6] 8296 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [7] 8297 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [8] 8298 0
HOCA @ Mater - South Brisbane
Recruitment hospital [9] 8299 0
St George Hospital - Kogarah
Recruitment hospital [10] 8300 0
Royal Hobart Hospital - Hobart
Recruitment hospital [11] 8301 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 16356 0
3004 - Prahran
Recruitment postcode(s) [2] 16357 0
3128 - Box Hill
Recruitment postcode(s) [3] 16358 0
2605 - Garran
Recruitment postcode(s) [4] 16359 0
2137 - Concord
Recruitment postcode(s) [5] 16360 0
2139 - Concord
Recruitment postcode(s) [6] 16361 0
5042 - Bedford Park
Recruitment postcode(s) [7] 16362 0
4102 - Woolloongabba
Recruitment postcode(s) [8] 16363 0
4101 - South Brisbane
Recruitment postcode(s) [9] 16364 0
2217 - Kogarah
Recruitment postcode(s) [10] 16365 0
7000 - Hobart
Recruitment postcode(s) [11] 16366 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 284911 0
Other Collaborative groups
Name [1] 284911 0
Australasian Leukaemia and Lymphoma Group
Country [1] 284911 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
Level 6, 372 Albert St.
East Melbourne, Vic., 3002.
Country
Australia
Secondary sponsor category [1] 283788 0
None
Name [1] 283788 0
Address [1] 283788 0
Country [1] 283788 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286910 0
Alfred Office of Ethics and Research Governance
Ethics committee address [1] 286910 0
Ethics committee country [1] 286910 0
Australia
Date submitted for ethics approval [1] 286910 0
01/06/2012
Approval date [1] 286910 0
14/01/2013
Ethics approval number [1] 286910 0

Summary
Brief summary
The outcome in patients with Multiple myeloma (MM) who fail to respond to treatment or relapse after treatment is extremely poor. This study plans to treat approximately 80 patients in a number of sites throughout Australia and aims to investigate the effect of pomalidomide (a type of chemotherapy drug) on the immune system, and in turn, whether the outcomes of treatment with pomalidomide as single agent therapy for relapsed/refractory multiple myeloma (a blood cancer) are different to that achieved by patients treated with pomalidomide and dexamethasone (a steroid treatment commonly used in this disease) combination therapy.

Who is it for?

This study is open to male or female patients aged 18 or above with a diagnosis of MM and failing previous therapy, either refractory or relapsed after at least 2 previous lines of chemotherapy (including lenalidomide). The full details of the inclusion and exclusion criteria can be found in the relevant sections within this record.

Trial details

Initially, all patients will receive induction therapy consisting of four 28 day cycles of pomalidomide and dexamethasone. Patients then randomised to the pomalidomide arm for maintenance treatment will receive 4mg oral pomalidomide daily on a cyclic 21-day out of 28-day schedule for approximately 12 cycles. Patients randomised to the control arm for maintenance treatment will receive 4mg oral pomalidomide daily on a cyclic 21-day out of 28-day schedule along with 40mg oral dexamethasone on days 1, 8, 15, & 22 of 28 day cycle for approximately 12 cycles. For each arm of the study, the actual cycle number will be determined by the patient's treating clinician and based on response to and tolerability of treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33508 0
Prof Andrew Spencer
Address 33508 0
Alfred Hospital Commercial Road Melbourne, Victoria, Australia, 3004
Country 33508 0
Australia
Phone 33508 0
+61 3 9076 3393
Fax 33508 0
Email 33508 0
[email protected]
Contact person for public queries
Name 16755 0
Ms Delaine Smith
Address 16755 0
Australasian Leukaemia and Lymphoma Group
Level 6, 372 Albert St.,
East Melbourne, Vic., 3002
Australia
Country 16755 0
Australia
Phone 16755 0
+61 3 96562760
Fax 16755 0
Email 16755 0
[email protected]
Contact person for scientific queries
Name 7683 0
Prof Andrew Spencer
Address 7683 0
Alfred Hospital
Commercial Road
Melbourne, Victoria, Australia, 3004
Country 7683 0
Australia
Phone 7683 0
+61 3 9076 3393
Fax 7683 0
Email 7683 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.