Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000605998
Ethics application status
Approved
Date submitted
7/06/2011
Date registered
14/06/2011
Date last updated
14/06/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase II trial of bortezomib and dexamethasone in
renally-impaired patients with untreated multiple myeloma.
Scientific title
A Phase II trial of bortezomib and dexamethasone in
renally-impaired patients with untreated multiple myeloma.
Secondary ID [1] 262341 0
Nil
Universal Trial Number (UTN)
Trial acronym
The BRIM Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Untreated Multiple Myeloma patients with renal impairment. 268033 0
Condition category
Condition code
Cancer 268162 268162 0 0
Myeloma
Blood 268176 268176 0 0
Haematological diseases
Renal and Urogenital 268177 268177 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Bortezomib 1.3mg/m2 IV on days 1, 4, 8, and 11. Dexamethasone 20mg oral on days 2, 4, 5, 8, 9, 11 and 12 on a 21 day cycle.
Patients whose disease does not achieve at least a partial remission after 2 cycles of therapy or shows disease progression at any time will be withdrawn from the trial. Patients eligible for high-dose chemotherapy conditioned stem cell transplant and who are responding to therapy will receive 4 cycles of therapy before proceeding to transplant. Non transplant eligible patients will receive a maximum of 11 cycles of therapy except those who achieve complete remission sooner who will have bortezomib therapy ceased after two further cycles and therefore may receive less than 11 cycles of therapy.
Intervention code [1] 266717 0
Treatment: Drugs
Comparator / control treatment
N/A
Control group
Uncontrolled

Outcomes
Primary outcome [1] 266907 0
To document the rate of renal response and reversal of renal impairment secondary to untreated MM following treatment with bortezomib and dexamethasone. This will be done by blood analysis.
Timepoint [1] 266907 0
During and at the end of each 21 day cycle.
Secondary outcome [1] 276599 0
To document the adverse events using bortezomib and dexamethasone in this patient population. This will be monitored by blood analysis, vital signs, patient's description of how they feel and by physical examination.
Patients receiving dexamethasone may experience hyperglycaemia, hypertension, myopathy, fluid retention, opportunistic infection, severe insomnia and depression.
Patients receiving bortezomib may experience various adverse events including thrombocytopenia, oedema, fatigue, peripheral neuropathy and GI disturbances.
Timepoint [1] 276599 0
During and at the end of each 21 day cycle.
Secondary outcome [2] 276600 0
To document time of renal response/reversal by blood analysis.
Timepoint [2] 276600 0
During and at the end of each 21 day cycle.
Secondary outcome [3] 276601 0
To conduct exploratory minimal residual disease studies in patients who obtain complete remission by blood and bone marrow analysis.
Timepoint [3] 276601 0
During and at the end of each 21 day cycle, and at the investigator's discretion.
Secondary outcome [4] 276602 0
To conduct exploratory proteomic analyses to attempt to correlate responsiveness to bortezomib with variations in multiple myeloma (MM) tumour cell protein expression profiles
Timepoint [4] 276602 0
During and at the end of each 21 day cycle.
Secondary outcome [5] 276603 0
The document the rate of dialysis independence by blood analysis.
Timepoint [5] 276603 0
During and at the end of each 21 day cycle.
Secondary outcome [6] 276604 0
To document the response rates of bortezomib and dexamethasone by blood and bone marrow analysis.
Timepoint [6] 276604 0
During and at the end of each 21 day cycle and at the discretion of the investigator.

Eligibility
Key inclusion criteria
- Renal impairment, secondary to MM, defined as a calculated estimated GFR <50ml/min,
- Able to provide written informed consent prior to the start of study-related procedures,
- Subject is, in the investigator's opinion, willing and able to comply with protocol requirements,
- If female, the subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control from signing of informed consent form through to the final visit/early termination visit.
- If male, the subject agrees to use an acceptable barrier method for contraception from signing of the informed consent through to the final visit/early termination visit.
- The patient meets the following pre-treatment laboratory criteria at and within 21 days before baseline:
*Platelet count >50x109/L, with or without transfusion support;
*Haemoglobin >7.0g/dL, with or without transfusion support;
*Absolute neutrophil count (ANC)>/=2.0x109/L;
*Serum calcium <4.5mmol/L (<14mg/dL);
*Aspartate Transaminase (AST) <2.5x the upper limit of normal;
*Alanine transaminase (ALT): <2.5x the upper limit of normal;
*Total bilirubin: <1.5x the upper limit of normal (exceptions will be made for patients diagnosed with Gilbert Syndrome);
*ECOG status 0-3.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Use of investigational agents within 28 days of study entry;
- Inadequate hepatic function;
- Severe co-morbidity or othe likely difficulty in completing the study;
- History of allergic reaction attributable to compounds containing boron or mannitol;
- Peripheral neuropathy or neuropathic pain Grade 2-4 defined by NCI CTCAE version 3;
- Uncontrolled or severe cardiovascular disease, including M1 within 6 months of enrolment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis;
- Subject has history of hypotension or has decreasing blood pressure (sitting systrolic blood pressure </=100mm/Hg and/or sitting diastolic blood pressure </=60mmHg;
- Subject has an active uncontrolled systemic infection requiring treatment;
- If female, the subject is pregnant or breastfeeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-HCG pregnancy test during screening. Pregnancy test is not required for post-menopausal or surgically steralised women;
- Anyy condition, that, in the opinion of the investigator, would compromise the well-being of the subject or the study.

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 found to have untreated multiple myeloma with renal impairment, and who are found to satisfy the described inclusion/exclusion criteria will be enrolled onto the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
8/04/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
28
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 267200 0
Commercial sector/Industry
Name [1] 267200 0
Janssen-Cilag Pty Ltd
Country [1] 267200 0
Australia
Primary sponsor type
Hospital
Name
Prof. Andrew Spencer
Address
The Alfred Hospital
Malignant Haematology and stem cell transplant Service
Ground Floor, William Buckland Building
Commercial Road
Prahran, 3181
Country
Australia
Secondary sponsor category [1] 266285 0
Hospital
Name [1] 266285 0
Prof. Andrew Spencer
Address [1] 266285 0
The Alfred Hospital
Malignant Haematology and stem cell transplant Service
Ground Floor, William Buckland Building
Commercial Road
Prahran, 3181
Country [1] 266285 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269192 0
Alfred Health Human Research Ethics Committee
Ethics committee address [1] 269192 0
The Alfred Hospital
Ground Floor, Linay Pavilion
55 Commercial Rd,
Prahran, 3182
Ethics committee country [1] 269192 0
Australia
Date submitted for ethics approval [1] 269192 0
01/08/2010
Approval date [1] 269192 0
08/04/2011
Ethics approval number [1] 269192 0
1/10/0272

Summary
Brief summary
This study aims to document the rate of renal response and reversal of renal impairment secondary to untreated multiple myeloma (MM) following treatment with Bortezomib and Dexamethasone. This will be done by blood analysis. Patients with untreated multiple myeloma will be selected by physicians. To ensure eligibility to go on trial the patients are required to undergo various blood tests, bone marrow aspirate ad doctor's review before commencing on this treatment. Who is it for? You may be eligible for this study if you are 18 years and over, have renal impairment secondary to MM, defined as a calculated estimated GFR <50ml/min. You must also provide written informed consent prior to the start of study-related procedures. Further details as to whether you are eligible for this study can be found in the inclusion and exclusion criteria within this trial record. Trial details Once you are deemed eligible to take part in this study, you will commence a 21 day cycle of Bortezomib 1.3mg/m2 IV given on days 1, 4, 8, and 11 and Dexamethasone 20mg oral on days 2, 4, 5, 8, 9, 11 and 12 on a 21 day cycle. If your disease does not achieve at least a partial remission after 2 cycles of therapy or shows disease progression at any time, you will be withdrawn from the trial. If you are eligible for high-dose chemotherapy conditioned stem cell transplant and have been responding to therapy, you will receive 4 cycles of therapy before proceeding to your transplant. If you are not eligible for a transplant, you will receive a maximum of 11 cycles of therapy except if you complete remission sooner, in which case you will have Bortezomib therapy ceased after two further cycles and therefore may receive less than 11 cycles of therapy. Treatment efficacy will be monitored throughout the study, at the end of each cycle and at the discretion of your treating doctors.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32707 0
Address 32707 0
Country 32707 0
Phone 32707 0
Fax 32707 0
Email 32707 0
Contact person for public queries
Name 15954 0
Lisa Di Maio
Address 15954 0
The Alfred Hospital
Malignant haematology and stem cell transplant service
Level 1, William Buckland Building
Commercial Rd
Prahran, Victoria, 3181
Country 15954 0
Australia
Phone 15954 0
+61 3 9076 3038
Fax 15954 0
Email 15954 0
L.DiMaio@alfred.org.au
Contact person for scientific queries
Name 6882 0
Lisa Di Maio
Address 6882 0
The Alfred Hospital
Malignant haematology and stem cell transplant
Level 1, William Buckland Building
Commercial Rd
Prahran, Victoria, 3181
Country 6882 0
Australia
Phone 6882 0
+61 3 9076 3038
Fax 6882 0
Email 6882 0
L.DiMaio@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

Documents added manually
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Documents added automatically
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