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Trial registered on ANZCTR


Registration number
ACTRN12617000958381
Ethics application status
Approved
Date submitted
26/06/2017
Date registered
4/07/2017
Date last updated
30/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A prospective Phase II study of Durvalumab Rescue for Inadequate response to Lenalidomide and Dexamethasone in transplant ineligible patients with newly diagnosed multiple myeloma
Scientific title
A prospective Phase II study of Durvalumab Rescue for Inadequate response to Lenalidomide and Dexamethasone in transplant ineligible patients with newly diagnosed multiple myeloma
Secondary ID [1] 292283 0
None
Universal Trial Number (UTN)
U1111-1198-3556
Trial acronym
DRIL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
multiple myeloma 303802 0
Condition category
Condition code
Cancer 303169 303169 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients given Lenalidomide as oral capsules, 25mg, daily on days 1 to 21 followed by a 7-day rest in a 28-day cycle and Dexamethasone as oral 4mg tablets, at a dose of 40mg (20mg for patients age >75 years) on days 1,8,15 and 22. Those patients not achieving partial response after 4 weeks of treatment, or very good partial response after 6 weeks of treatment or complete response after 9 weeks of treatment will be given Durvalumab at a dose of 1500mg IV on day 1 of the 28-day cycle. The IV infusion for subjects will be approximately 1 hour in duration.
Treatment will be given until disease progression or unacceptable toxicity, whichever occurs first.
All dosing is recorded by hospital staff. Drug accountability logs will be used by the hospital staff.
Intervention code [1] 298457 0
Treatment: Drugs
Comparator / control treatment
no control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302541 0
To assess whether the addition of Durvalumab to the regime of poor responders to lenalidomide-dexamethasone will increase the number of transplant ineligible patients reaching at least Partial Response as defined by the International Myeloma Working Group criteria.
Timepoint [1] 302541 0
Patients will be assessed for response at the end of every 28 day cycle up to six cycles of a lenalidomide/dexamethasone/Durvalumab regime.
Secondary outcome [1] 336349 0
To assess safety and tolerability of combination lenalidomide durvalumab and dexamethasone through biochemical analysis, physical examination and the monitoring of adverse events.
Timepoint [1] 336349 0
Assessments at the end of every 28 day cycle until cessation of treatment
Secondary outcome [2] 336350 0
To assess through exploratory biochemical analysis of serum samples immunological correlates to response and resistance to treatment.
Timepoint [2] 336350 0
After 3 cycles of lenalidomide/dexamethasone/Durvalumab treatment or at complete response or disease progression during the 6 lenalidomide/dexamethasone/Durvalumab treatment cycles.
Secondary outcome [3] 336440 0
To assess through exploratory biochemical analysis of serum samples molecular profile correlates to response and resistance to treatment.
Timepoint [3] 336440 0
After 3 cycles of lenalidomide/dexamethasone/Durvalumab treatment or at complete response or disease progression during the 6 lenalidomide/dexamethasone/Durvalumab treatment cycles.
Secondary outcome [4] 336441 0
To assess through exploratory biochemical analysis of serum samples proteomic correlates to response and resistance to treatment.
Timepoint [4] 336441 0
After 3 cycles of lenalidomide/dexamethasone/Durvalumab treatment or at complete response or disease progression during the 6 lenalidomide/dexamethasone/Durvalumab treatment cycles.

Eligibility
Key inclusion criteria
1. Male or Female patients, greater than or equal to 18 years of age
2. Either:
a). Treatment-naive multiple myeloma (diagnosis of MM as per Internatioal Myeloma Working Group definition) (ie. no prior therapies (except radiotherapy or short couse of corticosteroids equivalent to dexamethasone 160mg in the last 28 days)) OR
b). MM undergoing first line treatment with lenalidomide and dexamethasone AND have not completed four cycles of treatment AND is responding to treatment (ie. have not had progressive disease).
3. Measureable disease at diagnosis:
a). Serum M-protein greater than or equal to 5 g/L, or
b).Urine M-protein greater than or equal to 200 mg/24 hour, or
c). In patients without detectable serum or urine M-protein, serum free light chain (SFLC) greater than 100 mg/L (involved light chain) and an abnormal serum k/l ratio or
For IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) greater than or equal to 7500 mg/L (7.5 g/L).
4. Must be deemed ineligible for upfront autolgous stem cell transplant (ASCT).
5. ECOG performance status 0-2
6. Adequate liver function ( ALT, AST and GGT less than or equal to 2.5 x institutional upper limit of normal; GGT less than or equal to 1.5 x institutional upper limit of normal )
7. Creatinine clearance greater than 15ml/min
8. Platelet count greater than or equal to 50 x 109 (greater than or equal to 30 if bone marrow involvment by CD138+ myeloma cells exceeds 50percent of all nucleated cells on IHC).
9. Absolute neutrophil count greater than or equal to 1.0 x 109 (can be supported by growth factor support)
10. No contraindication to the use of any of the study drugs
11. No concomitant steroids other than dexamethasone outlined in this protocol
12. Patient has voluntarily agreed and has given written informed consent.
13. Life expectancy of greater than 12 weeks
14. All patients must be registered on and abide by the Celgene i-access Risk Management Program before receiving first dose of lenalidomide (www.iaccesscelgene.com). This program states the following requirement:
a). All females of childbearing potential (FCBP) must agree to have a negative pregnancy tests within 7 days of commencing each new cycle of lenalidomide and use two reliable methods of contraception simultaneously or to practice complete abstinence from any sexual contact during the following time periods related to this study: 1) for at least 28 days before starting study; 2) while participating in the study; 3) dose interruptions; and 4) for at least 28 days after study treatment discontinuation. The two methods of reliable contraception must include one highly effective method and one additional effective method).
b). All male participants must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with monoclonal gammopathy of uncertain significance or smouldering myeloma (as defined by IMWG)
2. Primary amyloidosis
3. Subjects who have had clinical evidence of central nervous system (CNS) or CNS multiple myeloma, or plasma cell leukemia
4. 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
5. Pregnant or lactating women.
6. Known Hepatitis B or Hepatitis C requiring treatment, HIV infection, other immunosuppressive therapy or autoimmune disease
7. Prior history of malignancies, other than MM, unless the subject has been free of the disease for greater than or equal to 5 years with the exception of the following non-invasive malignancies:
a. Basal cell carcinoma of the skin or level 1 melanoma that has been resected.
b. Squamous cell carcinoma of the skin
c. Carcinoma in situ of the cervix
d. Carcinoma in situ of the breast
e. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative
8. Known or suspected hypersensitivity to the excipients contained in the formulation of durvalumab, lenalidomide, or dexamethasone.
9. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of initiating study treatment
10. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis, Crohn’s disease], diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener’s syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves’ disease; rheumatoid arthritis; hypophysitis, uveitis) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
a. Subjects with vitiligo or alopecia;
b. Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement; or
c. Subjects with psoriasis not requiring systemic treatment;
11. Subject has incidence of gastrointestinal disease that may significantly alter the absorption of lenalidomide.
12. Receipt of live, attenuated vaccine within 30 days prior to the first dose of durvalumab (NOTE: subjects, if enrolled, should not receive live vaccine during the study and for 30 days after the last dose of durvalumab)
13. Unable or unwilling to undergo protocol required thromboembolism prophylaxis.
14. Females who are pregnant, nursing or breastfeeding, or intend to become pregnant during the participation to the study
15. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
16. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
17. Any condition that confounds the ability to interpret data from 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)
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
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Safety concerns
Date of first participant enrolment
Anticipated
7/08/2017
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
137
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 8443 0
St Vincent's Private Hospital - Fitzroy
Recruitment hospital [2] 8444 0
The Alfred - Prahran
Recruitment hospital [3] 8445 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 8446 0
Epworth Freemasons - Melbourne
Recruitment postcode(s) [1] 16515 0
3065 - Fitzroy
Recruitment postcode(s) [2] 16516 0
3004 - Prahran
Recruitment postcode(s) [3] 16517 0
3000 - Melbourne
Recruitment postcode(s) [4] 16518 0
3002 - Melbourne

Funding & Sponsors
Funding source category [1] 296825 0
Commercial sector/Industry
Name [1] 296825 0
Celgene Pty Ltd
Country [1] 296825 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australia Myeloma Research Consortium
Address
Alfred Hospital, Commercial Road, Melbourne, VIC, 3004
Country
Australia
Secondary sponsor category [1] 295817 0
None
Name [1] 295817 0
Address [1] 295817 0
Country [1] 295817 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298060 0
Alfred Health Human Research Ethics Committee
Ethics committee address [1] 298060 0
Alfred Hospital, Commercial Road, Melbourne, VIC, 3004
Ethics committee country [1] 298060 0
Australia
Date submitted for ethics approval [1] 298060 0
23/06/2017
Approval date [1] 298060 0
14/08/2017
Ethics approval number [1] 298060 0

Summary
Brief summary
The primary purpose of this trial is to assess whether the addition of durvalumab to patients who have achieved less than partial response to 4 cycles of lenalidomide and dexamethasone will cause an improvement in disease progression free survival.
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 not a candidate for high dose chemotherapy and autologous stem cell transplant.
Study details
Eligible participants will all receive lenalidomide and dexamethasone treatment in 28 day cycles, with those patients failing to adequately respond receiving durvalumab in addition. Treatment will continue until disease progression, unacceptable toxicity or patients otherwise coming off study. Participants will be required to have blood samples taken at the beginning of each cycle along with a medical examination to monitor treatment safety and whether it is effectively treating the myeloma. It is hoped that the findings of this trial will establish the benefits of durvalumab in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma patients early in the course of their disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75858 0
Dr Hang Quach
Address 75858 0
St.Vincent’s Hospital, 41 Victoria Pde, Fitzroy VIC 3065
Country 75858 0
Australia
Phone 75858 0
+61 3 9231 2211
Fax 75858 0
Email 75858 0
[email protected]
Contact person for public queries
Name 75859 0
Flora Yuen
Address 75859 0
Alfred Hospital, Commercial Road, Melbourne, Vic 3004
Country 75859 0
Australia
Phone 75859 0
+61 3 9076 5407
Fax 75859 0
+61 3 9076 5531
Email 75859 0
[email protected]
Contact person for scientific queries
Name 75860 0
Flora Yuen
Address 75860 0
Alfred Hospital, Commercial Road, Melbourne, Vic 3004
Country 75860 0
Australia
Phone 75860 0
+61 3 9076 5407
Fax 75860 0
+61 3 9076 5531
Email 75860 0
[email protected]

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
No documents have been uploaded by study researchers.

Documents added automatically
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