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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02046070
Ethics application status
Date submitted
12/12/2013
Date registered
27/01/2014

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
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
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
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
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
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
Timepoint [4] 0 0
Up to 1 year
Secondary outcome [5] 0 0
Duration of Response (DOR) in NDMM Participants
Timepoint [5] 0 0
Up to 45 Months
Secondary outcome [6] 0 0
Time to Progression (TTP) in NDMM Participants
Timepoint [6] 0 0
Up to 45 months
Secondary outcome [7] 0 0
Progression Free Survival (PFS) in NDMM Participants
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
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
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
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
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
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
Timepoint [19] 0 0
Up to 45 months
Secondary outcome [20] 0 0
Duration of Response (DOR) in RRMM Participants
Timepoint [20] 0 0
Up to 45 months
Secondary outcome [21] 0 0
Time to Progression (TTP) in RRMM Participants
Timepoint [21] 0 0
Up to 45 months
Secondary outcome [22] 0 0
Progression Free Survival (PFS) in RRMM Participants
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
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
Sex
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
5/03/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/06/2018
Sample size
Target
Accrual to date
Final
148
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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02046070