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Trial registered on ANZCTR


Registration number
ACTRN12614000301662
Ethics application status
Approved
Date submitted
30/01/2014
Date registered
21/03/2014
Date last updated
12/07/2023
Date data sharing statement initially provided
21/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase II study assessing the effect of carfilzomib treatment on early free light chain kinetics in myeloma patients with renal impairment
Scientific title
Phase II study assessing the effect of carfilzomib treatment on early free light chain kinetics in myeloma patients with renal impairment
Secondary ID [1] 284013 0
Nil
Universal Trial Number (UTN)
Trial acronym
ALLG MM16
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma with Renal Impairment 291050 0
Condition category
Condition code
Cancer 291391 291391 0 0
Myeloma
Renal and Urogenital 291799 291799 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Carfilzomib is a proteasome inhibitor and protease inibitors have been shown to be particularly effective in patients with renal failure, with an increased incidence of reversal or amelioration of renal impairment, and have been considered treatment-of-choice in MM patients presenting with renal failure.

Carfilzomib (IV) will be given on Days 1, 2, 8, 9, 15, 16 of a 4-week cycle for Cycles 1 to 9, followed by days 1, 2, 15, 16 in a 4-week cycle from Cycle 10. For the first 10 patients enrolled, the dose of carfilzomib will be 20 mg/m^2 on Cycle 1 Day 1, escalated to 27 mg/m^2 from Cycle 1 Day 8. Safety data will be analysed in these 10 patients, and if well tolerated the next 26-30 patients will be treated with a higher dose escalation, with 20 mg/m^2 on Cycle 1 Day 1, escalated to 56 mg/m^2 from Cycle 1 Day 8. In all patients carfilzomib will be administered in combination with dexamethasone 20 mg PO on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle.

For newly diagnosed patients who become transplant-eligible according to the assessment of the investigator, stem cell mobilisation may be performed after 4 cycles followed by autologous transplantation using the institutional protocol.

For newly diagnosed patients who are not eligible for transplant, after 10 cycles of carfilzomib, treatment is ceased when response assessment has indicated CR for 2 consecutive monthly assessments, or if CR is not achieved carfilzomib is continued until progression or toxicity.

For relapsed patients carfilzomib is continued until progression or toxicity.
Intervention code [1] 288697 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 291384 0
To assess the effect of carfilzomib on serum free light chain measurements early in the treatment of myeloma patients with renal impairment (eGFR 15 – 40 ml/min)
Timepoint [1] 291384 0
early in treatment-Serum free-light chain measurement (mg/L) at baseline (C1D1) and 48 hours post Cycle 1 Day 2 (i.e. C1D4).
Primary outcome [2] 291385 0
To determine if there is a relationship between changes in serum free light chain levels in the early phases of treatment and renal function after 4 cycles of treatment. Protein Electrophoresis and Immunofixation Electrophoresis will be used to measure serum free light chains. Renal function will be assessed by measuring eGFR using Creatinine values and the CKD-EPI formula.
Timepoint [2] 291385 0
Early in treatment-Serum free-light chain measurement (mg/L) at baseline (C1D1) and 48 hours post Cycle 1 Day 2 (i.e. C1D4), and after 4 cycles of treatment for renal function.
Secondary outcome [1] 306638 0
Nil
Timepoint [1] 306638 0
Nil

Eligibility
Key inclusion criteria
All of the following criteria must be satisfied for enrolment in the study.

Male and Female patients, >=18 years of age
Patients with newly diagnosed MM (diagnosis of MM as per IMWG –21)
Or
Multiple myeloma with relapsing or progressing disease at study entry,
With either
Measurable M-component in serum or urine,
In patients with no detectable M-component, an abnormal FLC ratio on the Serum FLC assay
For IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) >= 750 mg^dL (0.75 g^dL).

Patients with acute renal injury as the cause of reduced renal function, with creatinine clearance 15-40 ml^min at screening (calculated by the CKD-EPI and MDRD formulae)

Difference between involved and uninvolved free light chain >=300 mg^L

Adequate liver function (total bilirubin < 1.5 ULN, ALT < 2.5x ULN)

Absolute neutrophil count >= 1.0 x 109^L within one week of starting therapy.

Platelet count >= 50 x 109^L (>= 30 x 109^L if myeloma involvement in the marrow is greater than 50%) within one week of starting therapy, patients should not have received platelet transfusions within one week of the screening platelet count

Hb >= 80g^L, red cell transfusions as per institutional protocol are allowed

Subject must have LVEF >= 40%, determined by 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.

Has provided written informed consent

Males capable of parenting a child and females of childbearing potential must be using a medically acceptable and adequate method of contraception while undergoing protocol treatment and for 12 weeks after the last treatment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Presence of any of the following criteria will exclude the subject from enrolment in the study.

Patients who have had myocardial infarction within 6 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 at any time.

Other uncontrolled intercurrent illness including, but not limited to, severe active infection, or psychiatric illness/social situations that would limit compliance with study requirements

Evidence of infection, dehydration or hypercalcaemia as the cause of acute kidney injury that has not been corrected.

Patients on dialysis at Screening.

Patients with known amyloidosis.

Patients with myelodysplastic syndrome.

Known history of allergy to Captisol (a cyclodextrin derivative used to solubilise carfilzomib)

Patients with contraindication to dexamethasone.

Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment.

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

Known Hepatitis B, Hepatitis C, HIV infection, other immunosuppressive therapy including dexamethasone or autoimmune disease

Prior diagnosis of cancer that was:
more than 5 years prior to current diagnosis with subsequent evidence of disease recurrence or clinical expectation of recurrence is greater than 10%.
within 5 years of current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma or carcinoma in situ of the cervix.

Participation in other therapeutic studies in the last 60 days except for studies with a non-medical intervention. Documented evidence of receiving placebo will be required.

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
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
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/05/2014
Actual
2/04/2015
Date of last participant enrolment
Anticipated
Actual
20/02/2020
Date of last data collection
Anticipated
3/07/2022
Actual
3/07/2022
Sample size
Target
40
Accrual to date
Final
38
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 8045 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 8046 0
The Alfred - Prahran
Recruitment hospital [3] 8047 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [4] 8048 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 8049 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 16087 0
2050 - Camperdown
Recruitment postcode(s) [2] 16088 0
3004 - Prahran
Recruitment postcode(s) [3] 16089 0
2298 - Waratah
Recruitment postcode(s) [4] 16090 0
5000 - Adelaide
Recruitment postcode(s) [5] 16091 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 288635 0
Commercial sector/Industry
Name [1] 288635 0
Amgen (Europe) GmbH
Country [1] 288635 0
Switzerland
Primary sponsor type
Other Collaborative groups
Name
Australiasian Leukemia and Lymphoma Group
Address
35 Elizabeth St, Richmond, Vic, 3121.
Country
Australia
Secondary sponsor category [1] 287342 0
None
Name [1] 287342 0
Address [1] 287342 0
Country [1] 287342 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290490 0
Royal Prince Alfred Hospital
Ethics committee address [1] 290490 0
Ethics committee country [1] 290490 0
Australia
Date submitted for ethics approval [1] 290490 0
30/04/2014
Approval date [1] 290490 0
28/11/2014
Ethics approval number [1] 290490 0
Ethics committee name [2] 297737 0
The Alfred Ethics Committee
Ethics committee address [2] 297737 0
Ethics committee country [2] 297737 0
Australia
Date submitted for ethics approval [2] 297737 0
08/09/2014
Approval date [2] 297737 0
09/12/2014
Ethics approval number [2] 297737 0
436/14

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

Contacts
Principal investigator
Name 45938 0
Prof Joy Ho
Address 45938 0
Institute of Haematology
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Australia
Country 45938 0
Australia
Phone 45938 0
+61 2 9515 8031
Fax 45938 0
Email 45938 0
Joy.Ho1@health.nsw.gov.au
Contact person for public queries
Name 45939 0
Joy Ho
Address 45939 0
Institute of Haematology
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Australia
Country 45939 0
Australia
Phone 45939 0
+61 2 9515 8031
Fax 45939 0
Email 45939 0
Joy.Ho1@health.nsw.gov.au
Contact person for scientific queries
Name 45940 0
Joy Ho
Address 45940 0
Institute of Haematology
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Australia
Country 45940 0
Australia
Phone 45940 0
+61 2 9515 8031
Fax 45940 0
Email 45940 0
Joy.Ho1@health.nsw.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
Individual patient data will not be shared publically. Aggregate patient data and final results will be presented in the final report


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.