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Trial registered on ANZCTR


Registration number
ACTRN12619001199101p
Ethics application status
Not yet submitted
Date submitted
11/06/2019
Date registered
27/08/2019
Date last updated
27/08/2019
Date data sharing statement initially provided
27/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Frailty-stratified, randomised controlled Bayesian adaptive trial of bortezomib versus lenalidomide in transplant-ineligible myeloma (TI-NDMM) – the FRAIL-M study
Scientific title
Frailty-stratified, randomised controlled Bayesian adaptive trial of bortezomib versus lenalidomide in transplant-ineligible myeloma (TI-NDMM) – the FRAIL-M study
Secondary ID [1] 298413 0
AMARC 19-01
Secondary ID [2] 298509 0
ALLG MM22
Universal Trial Number (UTN)
Trial acronym
FRAIL-M
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 313126 0
Condition category
Condition code
Cancer 311601 311601 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Eligible patients will be randomised to received the either of the following:
- Velcade, Lenalidomide and Dexamethasone OR
- Velcade and Dexamethasone OR
- Lenalidomide and Dexamethasone

Lenalidomide will be administered at a dose of 10-25mg orally for Day 1 to 21 out of 28 Day cycle.
Velcade will be administered as subcutaneous injection at a dose of 1.0 - 1.3mg/m2 on Days 1, 8 and 15 out of 28 Day cycle. Dosage will be on body surface area and/or randmonised treatment arm.

Dexamethasone will be administered at a dose of 12-40mg orally on Days 1, 8 and 15 out of 28 Day cycle.

Dosages of each treatment will be based on body surface area and/or randmonised treatment arm.

All patients will continue on treatment until the either the development of progressive disease (PD), unacceptable toxicity, withdrawal of consent, or 6 years.

Adherence is monitored through hospital drug administration records and tablet adherence through drug packet return.
Intervention code [1] 314662 0
Treatment: Drugs
Comparator / control treatment
Lenalidomide and Dexamethasone
Control group
Active

Outcomes
Primary outcome [1] 320369 0
To determine the overall response rate (ORR) (Partial Response [PR] or better), within each of 3 frailty defined strata via the international uniform response criteria for multiple myeloma
Timepoint [1] 320369 0
After 4 cycles (28 days each cycle) of each allocated treatment regimen
Primary outcome [2] 320370 0
To determine the occurrence of deliverability-limiting toxicity (DeLT) within each of 3 frailty defined strata via participant reported adverse events (such as nausea)
Timepoint [2] 320370 0
Within the first 4 cycles of each allocated treatment regimen,
Secondary outcome [1] 371380 0
Determine Progression Free Survival via routine blood tests
Timepoint [1] 371380 0
At the completion of the study which is either progressive disease (PD), unacceptable toxicity, withdrawal of consent, or study closure.
Secondary outcome [2] 371381 0
Define patient frailty utilising the Frailty Index
Timepoint [2] 371381 0
At study baseline and completion of the study which is either progressive disease (PD), unacceptable toxicity, withdrawal of consent, or study closure.

Eligibility
Key inclusion criteria
1. Male and Female patients, equal to or greater 18 years of age.

2. Symptomatic NDMM as per IMWG criteria

3. Measurable disease as defined by a paraprotein 5g/L and/or an involved light chain isotype 100mg/l with an abnormal kappa:lambda ratio.

4. Not eligible for high-dose melphalan conditioned autologous stem cell transplantation (ASCT) due to age and/or co-morbidities.

5. No contraindication to the use of any of the study drugs.

6. Adequate liver function (total bilirubin less than 2.0x ULN, ALT less than 5.0x ULN) unless considered secondary to MM.

7. Adequate haematological parameters - Hb equal to or greater 80g/L (RBC transfusions as per institutional protocol are allowed); absolute neutrophil count equal to or greater 1.0 x 109/L; and, platelet count equal to or greater 50 x 109/L (equal to or greater 30 x 109/L if MM involvement in the marrow is greater than 50%) without platelet transfusion within 7 days of the screening platelet count.

8. Has provided written informed consent.

9. Women of childbearing potential must have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/mL performed before, during and after treatment.

10. Women of childbearing potential and male subjects who are sexually active with WOCP must agree to use 2 highly effective methods of contraception during the study and for 30 days following the last dose of study treatment including a male condom.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior treatment for MM apart from localised radiotherapy and/or a short course of steroids (dexamethasone 160mg or equivalent) for emergency management of MM related symptoms.

2. Patients who have had myocardial infarction within 3 months prior to enrolment, or NYHA (New York Hospital Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

3. Creatinine clearance <30ml/min that persists after correction of recognisable reversible factors e.g. hypercalcaemia, dehydration, sepsis etc.

4. Any other serious or uncontrolled medical or psychiatric illness that could, in the investigators opinion, potentially interfere with the completion of treatment according to this protocol.

5. Known ongoing or active systemic infection, active hepatitis B or C infection, or known human immunodeficiency (HIV) positivity.

6. Women who are pregnant or lactating. Women of child-bearing potential must have a negative urine pregnancy test at Screening.

7. Patient (to whom it is relevant) who is unable or unwilling to meet the requirements of the lenalidomide pregnancy prevention program.

8. Active malignancy with the exception of any of the following:
a. Adequately treated basal cell carcinoma, squamous cell carcinoma or in situ cervical cancer.
b. Adequately treated stage 1 cancer from which the subject is currently in remission from and has been in remission for > 2 years.
c. Stage 1 prostate cancer that does not require treatment.
d. Any other cancer from which the subject has been disease-free for > 2 years.

9. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.

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)
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
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet 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)
NSW,QLD,TAS,VIC

Funding & Sponsors
Funding source category [1] 302960 0
Government body
Name [1] 302960 0
Medical Research Future Fund
Address [1] 302960 0
Department of Health
GPO Box 9848
Canberra ACT 2601
Country [1] 302960 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia & Lymphoma Group
Address
35 Elizabeth St,
Richmond VIC 3121
Country
Australia
Secondary sponsor category [1] 302917 0
Other Collaborative groups
Name [1] 302917 0
Australasian Myeloma Research Consortium
Address [1] 302917 0
Alfred Hospital
55 Commercial Rd
Melbourne VIC 3004
Country [1] 302917 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 303515 0
Alfred Hospital Ethics Commitee
Ethics committee address [1] 303515 0
Alfred Health
55 Commercial Rd
Melbourne VIC 3004
Ethics committee country [1] 303515 0
Australia
Date submitted for ethics approval [1] 303515 0
02/09/2019
Approval date [1] 303515 0
Ethics approval number [1] 303515 0

Summary
Brief summary
The primary purpose of this trial is to assess appropriate treatment approach newly diagnosed with multiple myeloma with respect to frailty assessment .

Who is it for?
You may be eligible to participate in this trial if you are aged 18 years or over, have been newly diagnosed with multiple myeloma and are a candidate for chemotherapy but not for autologous stem cell transplant.

Study details
Eligible participants will be treated with their allocated treatment regimen (bortezomib or lenalidomide) through randmonisation. All patients will continue on treatment until the either the development of progressive disease (PD), unacceptable toxicity or withdrawal of consent.
Participants will be required to have blood samples taken at the beginning of each cycle along with a medical exam in order for researchers to monitor whether the treatment is safe and whether it is effectively treating the myeloma.
It is hoped that the findings of this trial will establish the most appropriate treatment approach in the context of the Australian re-imbursement environment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93930 0
Prof Andrew Spencer
Address 93930 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 93930 0
Australia
Phone 93930 0
+61 3 9076 2000
Fax 93930 0
Email 93930 0
aspencer@netspace.net.au
Contact person for public queries
Name 93931 0
Miss Flora Yuen
Address 93931 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 93931 0
Australia
Phone 93931 0
+61 3 9076 5407
Fax 93931 0
Email 93931 0
flora.yuen@alfred.org.au
Contact person for scientific queries
Name 93932 0
Prof Andrew Spencer
Address 93932 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 93932 0
Australia
Phone 93932 0
+61 3 9076 2000
Fax 93932 0
Email 93932 0
aspencer@netspace.net.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results