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Trial registered on ANZCTR


Registration number
ACTRN12618001490268
Ethics application status
Approved
Date submitted
28/08/2018
Date registered
5/09/2018
Date last updated
19/08/2019
Date data sharing statement initially provided
19/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Daratumumab-lenalidomide-dexamethasone (DRd) salvage for newly diagnosed Multiple Myeloma patients who fail bortezomib induction therapy
Scientific title
MM21 - A multicenter, single arm, study of daratumumab-lenalidomide-dexamethasone (DRd) for newly diagnosed transplant eligible multiple myeloma patients who fail bortezomib-based induction therapy.
Secondary ID [1] 295922 0
MM21
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Newly-diagnosed multiple myeloma 309408 0
Condition category
Condition code
Cancer 308263 308263 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
SALVAGE: Daratumumab will be given intravenously at a dose of 16mg/kg on days 1, 8, 15 and 22 of each 28-day cycle for cycles 1 and 2, and on days 1 and 15 of each 28-day cycle for cycles 3 and 4. Lenalidomide orally at a dose of 25mg once daily will be given on days 1-21 of each 28-day cycle for cycles 1 to 4. Dexamethasone at a dose of 40mg will be given on days 1, 8, 15 and 22 of each 28-day cycle for cycles 1 to 4.
After completing 3 cycles, patients will undergo a G-CSF mobilised peripheral blood stem cell (PBSC) collection. Following collection, patients will commence cycle 4 and undergo full disease re-evaluation after completion of study treatment.

Autologous Stem Cell Transplant(ASCT): Within 4 to 6 weeks of completion of cycle 4 all patients with greater than or equal to 2 million/kg CD34 cells available will undergo a melphalan 200mg/m2 conditioned ASCT as per standard institutional practice.

CONSOLIDATION: Commencing at between day 100 and 120 post-stem cell transplant patients without evidence of disease progression will commence consolidation. Consolidation cycles 1 to 12 will each be of 28 days duration. In consolidation cycles 1 and 2 patients will receive Daratumumab intravenously at a dose of 16mg/kg on days 1 and 15 and then on day 1 of each of cycles 3 to 12. Lenalidomide orally will be given at a dose of 25mg once daily on days 1-21 of cycles 1 and 2 and at a dose of 10mg once daily on days 1-28 of cycles 3 to 12. Dexamethasone at a dose of 40mg will be given on days 1, 8, 15 and 22 for cycles 1 to 12.

MAINTENANCE: After the completion of 12 cycles of consolidation patients will commence maintenance with Lenalidomide orally 10mg once daily (after 3 months increase to 15 mg/day if tolerated) until disease progression, unacceptable toxicity of the withdrawal of consent, for a maximum of 2 years treatment.
Intervention code [1] 312243 0
Treatment: Drugs
Intervention code [2] 312283 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307229 0
To determine the overall response rate (ORR) to Daratumumab-lenalidomide-dexamtheasone (DRd) salvage treatment (4 cycles of DRd) in newly-diagnosed transplant-eligible patients who have demonstrated either a sub-optimal response or refractoriness to bortezomib-based induction therapy. Response is assessed by International Myeloma Working Group guidelines and responses defined as achieving a partial response or greater.
Timepoint [1] 307229 0
The primary end point will be assessed when last patient recruited has completed disease evaluations following DRd salvage therapy, approximately 5 years post-enrolment.
Secondary outcome [1] 351195 0
To determine the Progression-free Survival (PFS) achieved with Daratumumab-lenalidomide-dexamtheasone (DRd) salvage therapy, Autologous Stem Cell Transplant (ASCT); DRd post-ASCT consolidation and Rituximab-maintenance. Survival status will be noted in the eCRF based on medical records.
Timepoint [1] 351195 0
Patients will be followed for PFS until approximately 5 years post-enrolment
Secondary outcome [2] 351474 0
To determine the Overall Survival (OS) achieved with Daratumumab-lenalidomide-dexamtheasone (DRd) salvage therapy, Autologous Stem Cell Transplant (ASCT); DRd post-ASCT consolidation and Rituximab-maintenance. Survival status will be noted in the eCRF based on medical records.
Timepoint [2] 351474 0
Patients will be followed for OS until approximately 5 years post-enrolment

Eligibility
Key inclusion criteria
1. Male and Female patients, greater than or equal to 18 years of age.
2. Symptomatic NDMM as per IMWG criteria
3. Eligible for high-dose melphalan conditioned ASCT.
4. Patients who have had a sub-optimal response to a bortezomib-based induction therapy, where a sub-optimal response is defined as:
The failure to achieve at least a minimal response (MR) with a minimum of 2 cycles of a prior bortezomib-based induction therapy OR a partial response (PR) with 4 cycles of a prior bortezomib-based induction therapy
OR are bortezomib refractory, that is, have progressed while on bortezomib therapy or within 60 days of receiving their last dose of bortezomib.
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. Absolute neutrophil count greater than or equal to 1.0 x 109/L.
8. Platelet count greater than or equal to 50 x 109/L (greater than or equal to 30 x 109/L if MM involvement in the marrow is greater than 50%), patients should not have received platelet transfusions within 7 days of the screening platelet count.
9. Hb greater than or equal to 80g/L, red cell transfusions as per institutional protocol are allowed.

Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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.
2. 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.
3. Known ongoing or active systemic infection, active hepatitis B or C infection, or known human immunodeficiency (HIV) positivity.
4. Subject has significant airways disease according to the following definitions:
a. Subject has known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) less than 50% of predicted normal.
b. Subject has had known moderate or severe persistent asthma within the last 2 years, or currently has uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
5. Women who are pregnant or lactating. Women of child-bearing potential must have a negative urine pregnancy test at Screening.
6. Any patient who is unable or unwilling to meet the requirements of the lenalidomide pregnancy prevention program.
7. 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 greater than 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 greater than 2 years.
8. 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.
9. Participation in other clinical trials for the treatment of multiple myeloma, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this 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
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)
ACT,NSW,QLD,SA,WA,VIC

Funding & Sponsors
Funding source category [1] 300520 0
Commercial sector/Industry
Name [1] 300520 0
Celgene
Address [1] 300520 0
607 St Kilda Road, Melbourne Victoria 3004
Country [1] 300520 0
Australia
Funding source category [2] 300521 0
Commercial sector/Industry
Name [2] 300521 0
Janssen-Cilag
Address [2] 300521 0
1-5 Khartoum Road, North Ryde New South Wales 2113
Country [2] 300521 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australiasian Leukaemia and Lymphoma Group
Address
35 Elizabeth St
Richmond VIC 3121
Country
Australia
Secondary sponsor category [1] 299996 0
None
Name [1] 299996 0
Address [1] 299996 0
Country [1] 299996 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301310 0
Alfred Health ethics committee
Ethics committee address [1] 301310 0
Alfred Hospital
99 Commercial Road
Melbourne VIC 3004
Ethics committee country [1] 301310 0
Australia
Date submitted for ethics approval [1] 301310 0
13/09/2018
Approval date [1] 301310 0
25/10/2018
Ethics approval number [1] 301310 0
45539

Summary
Brief summary
The purpose of this study is to assess whether a new combination of therapies, with stem cell transplant, will prolong remission and hold off recurrence of myeloma in patients who have been diagnosed with multiple myeloma and have not responded to standard treatment (currently Bortezomib).

Who is it for?

You may be eligible for this study if you are an adult who has been diagnosed with multiple myeloma and have had a minimal or no response to bortezomib based induction therapy.

Study details

If participants consent to take part in this study, they will receive the following:
- Four cycles of daratumumab, lenalidomide and dexamethasone. These medications will be used to alter the immune system response to myeloma cells.
- A transplant of their own, non-cancerous cells.
- This will be followed 12 cycles of the same medications given initially (daratumumab, lenalidomide and dexamethasone) to ‘consolidate’ treatment.
- After the completion of the 12 cycles, all participant will commence ‘maintenance’ phase of this study while involves daily doses of lenalidomide.

Patients will also undergo routine blood assessments as per standard of care

It is hoped that this treatment will provide an alternative treatment to those who have been diagnosed with multiple myeloma and have not responded to standard treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86586 0
Prof Andrew Spencer
Address 86586 0
Australian Centre For Blood Diseases
99 Commercial Road
Melbourne VIC 3004
Country 86586 0
Australia
Phone 86586 0
+61 3 990 30122
Fax 86586 0
Email 86586 0
aspencer@netspace.com
Contact person for public queries
Name 86587 0
Prof Andrew Spencer
Address 86587 0
Australian Centre For Blood Diseases
99 Commercial Road
Melbourne VIC 3004
Country 86587 0
Australia
Phone 86587 0
+61 3 990 30122
Fax 86587 0
Email 86587 0
aspencer@netspace.com
Contact person for scientific queries
Name 86588 0
Prof Andrew Spencer
Address 86588 0
Australian Centre For Blood Diseases
99 Commercial Road
Melbourne VIC 3004
Country 86588 0
Australia
Phone 86588 0
+61 3 990 30122
Fax 86588 0
Email 86588 0
aspencer@netspace.com

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