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Trial registered on ANZCTR


Registration number
ACTRN12615000188538
Ethics application status
Approved
Date submitted
2/02/2015
Date registered
26/02/2015
Date last updated
13/11/2019
Date data sharing statement initially provided
27/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
KIWI Study- Kyprolis based Induction in untreated Myeloma with Kyprolis post Transplant Consolidation
Scientific title
A Multicenter, Phase II study to assess the response rate of subjects with newly diagnosed Multiple Myeloma when treated with Carfilzomib (Kyprolis),Cyclophosphamide and Dexamethasone as induction followed by an autologous bone marrow transplant and Carfilzomib (Kyprolis), Thalidomide and Dexamethasone as consolidation.
Secondary ID [1] 286084 0
IST-CAR-588
Universal Trial Number (UTN)
U1111-1165-9492
Trial acronym
KIWI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 294083 0
Condition category
Condition code
Cancer 294391 294391 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 2, multicenter, open-label; non-randomized study in transplant-eligible patients with newly diagnosed Multiple Myeloma. Participants will receive the following:

Induction: Carfilzomib (Kyprolis) 56mg/m2 by intravenous infusion on D1, 2, 8, 9, 15,16 (except 20mg/m2 on D1 and 2 of the first cycle) Cyclophosphamide 300mg/m2 orally on D1, 8, 15 and Dexamethasone 20mg orally on D1, 2, 8, 9, 15 ,16 for five 28 day cycles.

Transplant: Stem cell mobilization will start following completion of the 5th induction cycle and will be done according to local institutional guidelines. Autologous bone marrow transplant will be done following stem cell collection also according to local institutional guidelines.
If patients become ineligible for transplant during the course of induction therapy or stem cell mobilization, Stem cell mobilization and/or autologous BMT can be omitted. Patients may then start consolidation therapy as below, if further treatment is not precluded.

Consolidation: Carfilzomib (Kyprolis) 56mg/m2 by intravenous infusion on D1, 2, 8, 9, 15,16. Thalidomide 100mg daily taken orally(continuously) Dexamethasone 20mg taken orally D1, 2, 8, 9, 15 ,16 for four 28 day cycles starting 3 months post Autologous Bone Marrow Transplant (ABMT)
Intervention code [1] 291077 0
Treatment: Drugs
Comparator / control treatment
In this study there is no comparator arm/control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294182 0
The primary objective is to assess the response rate of patients on this trial

Blood tests to measure immunoglobulin and serum free light chain values will be performed at the end of each cycle to assess disease response.
Bone marrow biopsies will also be performed at 4 time points (at screening, pre-transplant, at day 100 post transplant and on completion of the consolidation phase) to determine the depth of response by measuring minimal residual disease by flow cytometry.
Timepoint [1] 294182 0
Upon completion of post-transplant consolidation therapy
Secondary outcome [1] 312715 0
Safety and tolerability of the treatment.

Safety assessments will include the monitoring and assessment of all Adverse Events such as new medical problems or the worsening of existing medical problems, clinical laboratory parameters monitored by blood tests, and vital signs in relation to clinical study events.Patients will also undergo a physical exam by a doctor on day 1 of every cycle.

Participants will be given details of whom to contact in an emergency
Timepoint [1] 312715 0
During treatment and upto 30 days post last dose of study drug
Secondary outcome [2] 312716 0
Minimal Residual Disease (MRD) by transplant and by post transplant CarTD consolidation.
Timepoint [2] 312716 0
On completion of consolidation phase patients will undergo a bone marrow biopsy and MRD will be measured by flow cytometry using the Black Swan protocol.
Secondary outcome [3] 312717 0
Progression Free Survival (PFS)
Timepoint [3] 312717 0
Patients will be monitored for disease progression at each clinic visit by physical exam and laboratory testing (as per the treating centre’s policy) for 5 years after completion of therapy or until study closure or progressive disease.
Once progression is confirmed follow up for survival will continue.
Secondary outcome [4] 312929 0
Time to next treatment
Timepoint [4] 312929 0
Patients will be followed up at each clinic visit until a new treatment is commenced whereupon, follow up for survival will continue.
Secondary outcome [5] 312930 0
Overall survival
Timepoint [5] 312930 0
Patients will be followed for overall survival at clinic visits or by telephone annually (as per the treating centre’s policy) for 5 years after completion of therapy or until study closure.
For any subject who is lost to follow up, the study site will attempt to ascertain survival information via public database search

Eligibility
Key inclusion criteria
Disease-related:
1.Newly diagnosed symptomatic multiple myeloma

2.Transplant-eligible (according to local criteria)

Demographic:

3.Age 18- 70years

4.Life expectancy greater than or equal to 3 months

5.Eastern Cooperative Oncology Group (ECOG) performance status 0–2

Laboratory

6.Adequate hepatic function, with serum ALT less than or equal to 3.5 times the upper limit of normal and serum direct bilirubin less than or equal to 34 micromol/L within 14 days prior to enrollment

7.Absolute neutrophil count (ANC) greater than or equal to 1.0 × 109/L within 14 days prior to enrollment

8.Hemoglobin greater than or equal to 80 g/L within 14 days prior to enrollment (subjects may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines)

9.Platelet count greater than or equal to 50× 109/L (equal to 30 × 109/L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to enrollment

10.Creatinine clearance (CrCl) greater than or equal to 15 mL/minute within 7 days prior to enrollment, either measured or calculated using a standard formula (eg, Cockcroft and Gault)

Ethical/Other

11.Written informed consent in accordance with local, and institutional guidelines.

12.Women of childbearing potential must have a negative serum pregnancy test within the 7 days prior to study drug administration and a negative urine pregnancy test within the 3 days prior to the first study drug administration.

13.Women of childbearing potential and male subjects who are sexually active with WOCBP 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
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Disease-related
1. Multiple Myeloma of IgM subtype.

2. Glucocorticoid therapy within 14 days prior to enrollment that equals or exceeds a cumulative dose of 160 mg of dexamethasone.

3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).

4. Plasma cell leukemia (greater than 2.0 × 109/L circulating plasma cells by standard differential).

5. Waldenstrom macroglobulinemia (WM).

6. Known amyloidosis.

7. Any immunotherapy for myeloma within 21 days prior to enrollment.


Concurrent Conditions

8.Pregnant or lactating females

9.Major surgery within 21 days prior to enrollment(unless related to myeloma)

10.Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment

11.Known human immunodeficiency virus infection

12.Active hepatitis B or C infection

13.Unstable angina or myocardial infarction within 4 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker

14. Pulmonary Hypertension

15.LVEF of less than 40%

16.Uncontrolled hypertension or uncontrolled diabetes

17.Nonhematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas

18.Significant neuropathy (Grades 3–4, or Grade 2 with pain) within 14 days prior to enrollment

19.Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)

20.Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment

21.Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment

22.Any other clinically significant medical disease or condition that, in the Investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent

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)
Newly diagnosed symptomatic multiple myeloma
Transplant-eligible (according to local criteria)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
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)
Safety/efficacy
Statistical methods / analysis
We have analyzed local results of transplant eligible untreated multiple myeloma patients treated with cyclophosphamide, bortezomib and dexamethasone (CyBorD) x 5-6 prior to transplant, followed by bortezomib, thalidomide and dexamethasone (VTD x 3-4) post transplant. The CR rate at 12 months was 28%. If the rate of CR at 12 months following carfilzomib, cyclophosphamide, dexamethasone (CarCD) x5, autologous BMT and carfilzomib, thalidomide, dexamethasone( CarTD )was 55%, using Chi-squared test of 0.5 (1-sided) and a power of 80%, the sample size required would be 48.


Recruitment
Recruitment status
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 outside Australia
Country [1] 6622 0
New Zealand
State/province [1] 6622 0
Auckland

Funding & Sponsors
Funding source category [1] 290671 0
Commercial sector/Industry
Name [1] 290671 0
Amgen Inc
Address [1] 290671 0
One Amgen Center Drive
Thousand Oaks
California USA 91320
Country [1] 290671 0
United States of America
Primary sponsor type
Other
Name
North Shore Haematology Clinical Trial Unit
Address
North Shore Hospital
124 Shakespeare Road
Takapuna
Auckland 0622
Country
New Zealand
Secondary sponsor category [1] 289364 0
None
Name [1] 289364 0
Address [1] 289364 0
Country [1] 289364 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292301 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 292301 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 292301 0
New Zealand
Date submitted for ethics approval [1] 292301 0
10/02/2015
Approval date [1] 292301 0
29/04/2015
Ethics approval number [1] 292301 0
15/NTB/49

Summary
Brief summary
This study will determine the effectiveness of a Carfilzomib (Kyprolis) based induction with autologous bone marrow transplant and Carfilzomib (Kyprolis) post-transplant consolidation in patients with untreated Myeloma.
Who is it for? You may be eligible to join this study if you are aged 18 years or above, have been newly diagnosed with symptomatic multiple myeloma and are eligible for bone marrow transplant.

Study details: All participants in this study will receive 5 cycles of Carfilzomib (Kyprolis) 56mg/m2 by intravenous infusion (i.e. directly into the vein) on Days 1, 2, 8, 9, 15,16 (except 20mg/m2 on Day 1 and 2 of the first cycle) Cyclophosphamide 300mg/m2 orally on Days 1, 8, 15 and Dexamethasone 20mg orally on Days 1, 2, 8, 9, 15, 16 for five 28 day cycles. This will be followed by a stem cell collection and autologous bone marrow transplant according to local institutional guidelines.
Post-transplant consolidation therapy will consist of 4 cycles of Carfilzomib (Kyprolis) 56mg/m2 by intravenous infusion (i.e. directly into the vein) on days 1, 2, 8, 9, 15,16 Thalidomide 100mg daily orally (continuously), Dexamethasone 20mg orally on Days 1, 2, 8, 9, 15 ,16 for four 28 day cycles starting 3 months post-transplant.
The study will monitor the disease response, adverse events, progression free survival and overall survival in each patient for up to 5 years.

Carfilzomib (Kyprolis) is not registered for use by Medsafe in New Zealand but has been approved by the FDA. Cyclophosphamide and Dexamethasone are approved drugs currently being used to treat Myeloma.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 54546 0
Dr Henry Chan
Address 54546 0
North Shore Hospital
124 Shakespeare Road
Takapuna
Auckland 0622
Country 54546 0
New Zealand
Phone 54546 0
+6494868920
Fax 54546 0
+64 9 488 4641
Email 54546 0
henry.chan@waitematadhb.govt.nz
Contact person for public queries
Name 54547 0
Mrs Elizabeth Thatcher
Address 54547 0
Haematology research
Level 2, OP, Kahui Manaaki, Bld 5,
North Shore Hospital
124 Shakespeare Road
Takapuna, Auckland 0622
Country 54547 0
New Zealand
Phone 54547 0
+64 8 486 8920 ext 42185
Fax 54547 0
+64 9 486 8331
Email 54547 0
elizabeth.thatcher@waitematadhb.govt.nz
Contact person for scientific queries
Name 54548 0
Dr Henry Chan
Address 54548 0
North Shore Hospital
124 Shakespeare Road
Takapuna
Auckland 0622
Country 54548 0
New Zealand
Phone 54548 0
+6494868920
Fax 54548 0
+64 9 488 4641
Email 54548 0
henry.chan@waitematadhb.govt.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual Participant Data will not be shared. However the results of the trial will be made available to all participating investigators and Amgen.
A summary of study outcomes will be provided to patients
Outcomes of the study will be shared via articles in peer reviewed scientific journals, internal reports, conference presentations, submissions to regulatory authorities (e.g. Medsafe)
What supporting documents are/will be available?
No other documents available
Summary results
No Results