The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02046070




Registration number
NCT02046070
Ethics application status
Date submitted
12/12/2013
Date registered
27/01/2014
Date last updated
17/07/2019

Titles & IDs
Public title
Phase 2 Study to Evaluate the Oral Combination of Ixazomib (MLN9708) With Cyclophosphamide and Dexamethasone in Patients With Newly Diagnosed or Relapsed and/or Refractory Multiple Myeloma
Scientific title
An Open-Label, Phase 2 Study to Evaluate the Oral Combination of Ixazomib (MLN9708) With Cyclophosphamide and Dexamethasone in Patients With Newly Diagnosed or Relapsed and/or Refractory Multiple Myeloma Requiring Systemic Treatment
Secondary ID [1] 0 0
2013-003113-17
Secondary ID [2] 0 0
C16020
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Ixazomib
Treatment: Drugs - Dexamethasone

Experimental: Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) - Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity [13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months] and cyclophosphamide (CYC) 300 mg/m^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients >75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.

Experimental: Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) - Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity [13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months] and cyclophosphamide (CYC) 400 mg/m^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients >75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.

Experimental: Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM) - Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle and cyclophosphamide 300 mg/m^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients >75 years) of a 28-day cycle until PD/death or unacceptable toxicity in participants with RRMM.


Treatment: Drugs: Cyclophosphamide
Cyclophosphamide tablets

Treatment: Drugs: Ixazomib
Ixazomib capsules

Treatment: Drugs: Dexamethasone
Dexamethasone tablets

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Combined Response Rate During the Induction Phase in Newly Diagnosed Multiple Myeloma (NDMM) Participants - Combined Response Rate is the percentage of participants with Complete Response (CR), including stringent Complete Response (sCR), and Very Good Partial Response (VGPR) according to the International Myeloma Working Group (IMWG) criteria during the Induction Phase (Cycles 1-13, 28-day cycles). CR=negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour.
Timepoint [1] 0 0
Day 1 of Cycles 1-13, 28-day cycles (Up to 1 year)
Primary outcome [2] 0 0
Overall Response Rate (ORR) in Relapsed and/or Refractory Multiple Myeloma (RRMM) Participants - ORR is the percentage of participants with CR, VGPR or PR according to IMWG criteria. CR=negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells (PC) in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved free light chain (FLC) levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas.
Timepoint [2] 0 0
Day 1 of each 28 day cycle (Up to 45 months)
Secondary outcome [1] 0 0
Number of Participants With Adverse Events (AEs), Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction and Serious Adverse Events (SAEs) in NDMM Participants - An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug.
A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug was determined by the Investigator.
Timepoint [1] 0 0
First dose of study drug through 30 days after last dose of drug (Up to 45 months)
Secondary outcome [2] 0 0
Percentage of Participants With CR + VGPR + PR (ORR), CR, VGPR, PR and Stable Disease (SD), Progressive Disease (PD) During the Induction Phase - Percentage of participants with CR + VGPR + PR (ORR), CR, VGPR, PR, SD, PD according to IMWG criteria. CR=negative immunofixation of serum and urine; disappearance of soft tissue plasmacytomas;<5% PC in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved FLC levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas. SD=not meeting criteria for VGPR, PR or PD. PD=25% increase in lowest value any of the following: serum M-component, urine M-component, difference between involved and uninvolved FLC levels, bone marrow PC percentage; new or increase in size of existing bone lesions or soft tissue plasmacytomas.
Timepoint [2] 0 0
Day 1 of Cycles 1-13, 28-day cycles (Up to 1 year)
Secondary outcome [3] 0 0
Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants - Percentage of participants with CR + VGPR + PR (ORR), CR, VGPR, PR, SD, PD according to IMWG criteria. CR=negative immunofixation of serum and urine; disappearance of soft tissue plasmacytomas;<5% PC in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved FLC levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas. SD=not meeting criteria for VGPR, PR or PD. PD=25% increase in lowest value any of the following: serum M-component, urine M-component, difference between involved and uninvolved FLC levels, bone marrow PC percentage; new or increase in size of existing bone lesions or soft tissue plasmacytomas.
Timepoint [3] 0 0
Day 1 of each 28-day Cycle (Up to 45 months)
Secondary outcome [4] 0 0
Time to Response (TTR) in NDMM Participants During the Induction Phase - TTR is defined as the time interval from the date of the first dose of study treatment to the date of the first documented confirmed response of PR or better up to the initiation of alternative therapy in a participant who responded.
Timepoint [4] 0 0
Up to 1 year
Secondary outcome [5] 0 0
Duration of Response (DOR) in NDMM Participants - DOR is defined as the time from the date of first documentation of a confirmed PR or better to the date of first documented PD up to the initiation of alternative therapy.
Timepoint [5] 0 0
Up to 45 Months
Secondary outcome [6] 0 0
Time to Progression (TTP) in NDMM Participants - TTP is defined as the time from the date of first dose of study treatment to the date of first documentation of disease progression.
Timepoint [6] 0 0
Up to 45 months
Secondary outcome [7] 0 0
Progression Free Survival (PFS) in NDMM Participants - PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression or death.
Timepoint [7] 0 0
Up to 45 months
Secondary outcome [8] 0 0
Number of Participants With AEs, SAEs, AEs Resulting in Discontinuation and AEs Resulting in Dose Reduction in NDMM Participants Remaining on Treatment After 13 Cycles - An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug.
A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug was determined by the Investigator.
Timepoint [8] 0 0
First dose of study drug through 30 days after the last dose of drug (Up to 45 months)
Secondary outcome [9] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants - EORTC QLQ-C30 is a patient completed 30 item questionnaire that consists of 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The patient evaluates their health status over the previous week. There are 28 questions answered on a 4-point scale where1=Not at all (best) to 4=Very Much (worst) and 2 questions answered on a 7-point scale where 1=Very poor (worst) to 7= Excellent (best). All of the scales and single-item measures are transformed to a score:0 to 100. For functioning scales and global QOL higher scores indicate better functioning (a positive change from Baseline indicates improvement); for symptom scales higher scores indicate more severe symptoms (a negative change from Baseline indicates improvement).
Timepoint [9] 0 0
Baseline (BL) (Day 1 of Cycle 1), Day 1 of Cycle 13 (Up to 1 year)
Secondary outcome [10] 0 0
Percentage of Participants With CR + VGR + PR (ORR), CR, VGPR, and PR in NDMM Participants Remaining on Treatment After 13 Cycles - Percentage of participants with Overall Response (CR + VGPR + PR), CR, VGPR and PR according to IMWG criteria. CR=negative immunofixation of serum and urine; disappearance of soft tissue plasmacytomas;<5% PC in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved FLC levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas.
Timepoint [10] 0 0
Day 1 of each 28-day Cycle (Up to 45 months)
Secondary outcome [11] 0 0
Cmax: Maximum Observed Plasma Concentration for Ixazomib in NDMM Participants
Timepoint [11] 0 0
Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose
Secondary outcome [12] 0 0
Tmax: Time to First Occurrence of Cmax for Ixazomib in NDMM Participants
Timepoint [12] 0 0
Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose
Secondary outcome [13] 0 0
AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in NDMM Participants
Timepoint [13] 0 0
Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose
Secondary outcome [14] 0 0
Number of Participants With AEs, Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction, SAEs in RRMM Participants - An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment.
A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug was determined by the Investigator.
Timepoint [14] 0 0
First dose of study drug through 30 days after last dose of drug (Up to 45 months)
Secondary outcome [15] 0 0
Cmax: Maximum Observed Plasma Concentration for Ixazomib in RRMM Participants
Timepoint [15] 0 0
Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose
Secondary outcome [16] 0 0
Tmax: Time to First Occurrence of Cmax for Ixazomib in RRMM Participants
Timepoint [16] 0 0
Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168) hours postdose
Secondary outcome [17] 0 0
AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in RRMM Participants
Timepoint [17] 0 0
Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose
Secondary outcome [18] 0 0
Percentage of Participants With (CR + VGPR), CR, VGPR, PR, SD and PD in RRMM Participants - Percentage of participants with CR + VGPR + PR (ORR), CR, VGPR, PR, SD, PD according to IMWG criteria. CR=negative immunofixation of serum and urine; disappearance of soft tissue plasmacytomas;<5% PC in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved FLC levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas. SD=not meeting criteria for VGPR, PR or PD. PD=25% increase in lowest value any of the following: serum M-component, urine M-component, difference between involved and uninvolved FLC levels, bone marrow PC percentage; new or increase in size of existing bone lesions or soft tissue plasmacytomas.
Timepoint [18] 0 0
Day 1 of each 28-day Cycle (Up to 45 months)
Secondary outcome [19] 0 0
Time to Response (TTR) in RRMM Participants - TTR is defined as the time interval from the date of the first dose of study treatment to the date of the first documented confirmed response of PR or better up to the alternative therapy in a participant who responded.
Timepoint [19] 0 0
Up to 45 months
Secondary outcome [20] 0 0
Duration of Response (DOR) in RRMM Participants - DOR is defined as the time from the date of first documentation of a confirmed PR or better to the date of first documented PD up to the alternative therapy.
Timepoint [20] 0 0
Up to 45 months
Secondary outcome [21] 0 0
Time to Progression (TTP) in RRMM Participants - TTP is defined as the time from the date of first dose of study treatment to the date of first documentation of disease progression.
Timepoint [21] 0 0
Up to 45 months
Secondary outcome [22] 0 0
Progression Free Survival (PFS) in RRMM Participants - PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression or death.
Timepoint [22] 0 0
Up to 45 months
Secondary outcome [23] 0 0
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants - EORTC QLQ-C30 is a patient completed 30 item questionnaire that consists of 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The patient evaluates their health status over the previous week. There are 28 questions answered on a 4-point scale where1=Not at all (best) to 4=Very Much (worst) and 2 questions answered on a 7-point scale where 1=Very poor (worst) to 7= Excellent (best). All of the scales and single-item measures are transformed to a score:0 to 100. For functioning scales and global QOL higher scores indicate better functioning (a positive change from Baseline indicates improvement); for symptom scales higher scores indicate more severe symptoms (a negative change from Baseline indicates improvement).
Timepoint [23] 0 0
Baseline (Day 1 of Cycle 1), Day 1 of End of Treatment (EOT) (Up to 45 months)

Eligibility
Key inclusion criteria
Each participant with newly diagnosed multiple myeloma (NDMM) must meet all of the
following inclusion criteria to be enrolled in the study:

1. Adult male or female participants 18 years of age or older with a confirmed diagnosis
of symptomatic multiple myeloma (MM) according to standard criteria.

2. Participants for whom cyclophosphamide and dexamethasone treatment is appropriate and
who are considered not eligible for high-dose therapy (HDT)-stem cell transplantation
(SCT) for 1 or more of the following reasons:

- The participant is 65 years of age or older.

- The participant is less than 65 years of age but has significant comorbid
condition(s) that are, in the opinion of the investigator, likely to have a
negative impact on tolerability of HDT-SCT.

Each participant with relapsed and/or refractory multiple myeloma (RRMM) must meet all of
the following inclusion criteria to be enrolled in the study:

1. Adult male or female participants 18 years or older with a confirmed diagnosis of
symptomatic MM either currently or at the time of initial diagnosis, according to
standard criteria, and relapsed and/or refractory disease after 1 to 3 lines of prior
therapy. A participant is considered to have refractory disease if disease progression
occurred during the treatment period or within 60 days of receiving the last dose of a
given therapy. A line of therapy is defined as 1 or more cycles of a single-agent or
combination therapy or a sequence of planned treatments such as induction therapy
followed by autologous stem cell transplantation (ASCT) and then maintenance therapy.

2. No evidence of graft-versus-host disease for participants who have undergone prior
allogeneic stem cell transplantation.

In addition, all participants (NDMM and RRMM) must meet all of the remaining criteria:

1. Participants must have measurable disease defined by at least 1 of the following 3
measurements:

- Serum M-protein = 1 g/dL (= 10 g/L).

- Urine M-protein = 200 mg/24 hours.

- Serum free light chain assay: involved free light chain level = 10 mg/dL (= 100
mg/L), provided that the serum free light chain ratio is abnormal.

2. Participants must meet all of the following clinical laboratory criteria:

- Absolute neutrophil count (ANC) = 1000/mm^3 and platelet count = 75,000/mm^3.
Platelet transfusions to help participants meet eligibility criteria are not
allowed within 3 days prior to administration of the study drug.

- Total bilirubin = 1.5 x the upper limit of the normal range (ULN).

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x ULN.

- Calculated creatinine clearance (CrCL) = 30 mL/min.

3. Eastern Cooperative Oncology Group performance status of 0, 1, or 2.

4. Female participants who:

- are postmenopausal for at least 1 year before the screening visit, or

- are surgically sterile, or

- If they are of childbearing potential, agree to practice 2 effective methods of
contraception, at the same time, from the time of signing the informed consent
through 90 days after the last dose of study drug, or

- agree to practice true abstinence over the period previously described, when this
is in line with the preferred and usual lifestyle of the participant. (Periodic
abstinence [ie, calendar, ovulation, symptothermal, postovulation methods] and
withdrawal are not acceptable methods of contraception.), and

- adhere to any treatment-specific pregnancy prevention guidelines for
cyclophosphamide and dexamethasone.

5. Male participants, even if surgically sterilized (ie, status post-vasectomy), who:

- agree to practice effective barrier contraception during the entire study
treatment period and through 90 days after the last dose of study drug, or

- agree to practice true abstinence over the period previously described, when this
is in line with the preferred and usual lifestyle of the participant. (Periodic
abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the
female partner] and withdrawal are not acceptable methods of contraception.), and

- adhere to any treatment-specific pregnancy prevention guidelines for
cyclophosphamide and dexamethasone.

6. Voluntary written consent must be given before performance of any study-related
procedure not part of standard medical care, with the understanding that consent may
be withdrawn by the participant at any time without prejudice to future medical care.

7. Suitable venous access for the study-required blood sampling.

8. Is willing and able to adhere to the study visit schedule and other protocol
requirements.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior treatment for multiple myeloma with either standard of care treatment or
investigational regimen (for participants with NDMM only).

NOTE: Prior treatment with corticosteroids (maximum dose of corticosteroids should not
exceed the equivalent of 160 mg of dexamethasone over 14 days. Localized radiation is
permitted as long as it is below a therapeutic level and administered at least 14 days
prior to the first dose of study treatment.

2. Diagnosis of smoldering MM, Waldenström's macroglobulinemia, POEMS (polyneuropathy,
organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome,
plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or
myeloproliferative syndrome.

3. Central nervous system involvement.

4. Diagnosed or treated for another malignancy within 2 years before the first dose or
previously diagnosed with another malignancy and have any evidence of residual
disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type
are not excluded if they have undergone complete resection.

5. Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of
any cause on clinical examination during the Screening period.

6. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
absorption or tolerance of study drug, including difficulty swallowing.

7. Infection requiring intravenous (IV) antibiotic therapy or other serious infection
within 14 days before the first dose of study drug.

8. Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active
hepatitis B or C infection.

9. Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin,
ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin,
itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A
inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital),
or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of
study treatment.

10. Known allergy to any of the study medications, their analogues, or excipients in the
various formulations.

11. Major surgery within 14 days before the first dose of study drug. (Note: kyphoplasty
or vertebroplasty is not considered major surgery.)

12. Female participants who are lactating and breastfeeding or have a positive serum
pregnancy test during the Screening period.

13. Any serious medical or psychiatric illness that could, in the investigator's opinion,
potentially interfere with the completion of treatment according to this protocol.

14. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the participant inappropriate for entry into this
study or interfere significantly with the proper assessment of safety and toxicity of
the prescribed regimens.

15. Treatment with any investigational products for reasons other than MM within 30 days
before the first dose of study drug.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
NSW,SA,VIC
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- Concord
Recruitment hospital [3] 0 0
- Waratah
Recruitment hospital [4] 0 0
- Adelaide
Recruitment hospital [5] 0 0
- Heidelberg
Recruitment hospital [6] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Concord
Recruitment postcode(s) [3] 0 0
- Waratah
Recruitment postcode(s) [4] 0 0
- Adelaide
Recruitment postcode(s) [5] 0 0
- Heidelberg
Recruitment postcode(s) [6] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Kentucky
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
Greece
State/province [7] 0 0
Attiki
Country [8] 0 0
Greece
State/province [8] 0 0
Athens
Country [9] 0 0
Greece
State/province [9] 0 0
Patras
Country [10] 0 0
Greece
State/province [10] 0 0
Thessaloniki
Country [11] 0 0
Poland
State/province [11] 0 0
Lubelskie
Country [12] 0 0
Poland
State/province [12] 0 0
Mazowieckie
Country [13] 0 0
Poland
State/province [13] 0 0
Chorzow
Country [14] 0 0
Poland
State/province [14] 0 0
Gdansk
Country [15] 0 0
Poland
State/province [15] 0 0
Lodz
Country [16] 0 0
Sweden
State/province [16] 0 0
Skane lAN
Country [17] 0 0
Sweden
State/province [17] 0 0
Sodermanlands LAN
Country [18] 0 0
Sweden
State/province [18] 0 0
Lund

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Millennium Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase 2, multicenter, open-label study in patients with Newly Diagnosed Multiple
Myeloma (NDMM) who have not received prior systemic treatment for multiple myeloma (MM) and
who are ineligible for high-dose therapy (HDT)-stem cell transplantation (SCT) due to age
(ie, = 65 years) or comorbid disease(s) or with Relapsed and/or Refractory Multiple Myeloma
(RRMM).
Trial website
https://clinicaltrials.gov/show/NCT02046070
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Millennium Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications