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/NCT03785184




Registration number
NCT03785184
Ethics application status
Date submitted
20/12/2018
Date registered
20/12/2018
Date last updated
20/12/2018

Titles & IDs
Public title
A Study of Venetoclax Plus Lenalidomide and Dexamethasone for the Treatment of Newly Diagnosed t(11;14)-Positive Multiple Myeloma in Subjects Who Are Ineligible for High-Dose Therapy
Scientific title
A Phase 2, Multicenter, Single Arm, Open Label Study of Venetoclax Plus Lenalidomide and Dexamethasone for the Treatment of Newly Diagnosed t(11;14)-Positive Multiple Myeloma in Subjects Who Are Ineligible for High-Dose Therapy
Secondary ID [1] 0 0
M16-104
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 - venetoclax
Treatment: Drugs - lenalidomide
Treatment: Drugs - dexamethasone

Experimental: Venetoclax + Lenalidomide + Dexamethasone - Venetoclax up to 800 mg orally every day (QD) QD on Days 1 - 28 plus lenalidomide up to 25 mg orally QD on Days 1 - 21 (28 day cycle) plus dexamethasone up to 40 mg orally once weekly (QW).


Treatment: Drugs: venetoclax
tablet; oral

Treatment: Drugs: lenalidomide
capsule; oral

Treatment: Drugs: dexamethasone
tablet; oral

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

Outcomes
Primary outcome [1] 0 0
Percentage of Participates Who Achieve CR - Complete response (CR) is defined as negative immunofixation of serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow.
Timepoint [1] 0 0
From baseline up to approximately 24 months
Secondary outcome [1] 0 0
Percent of Participants Who Achieve MRD Negativity - Minimal residual disease (MRD) negative after treatment is described as less than one myeloma cell per 100,000 bone marrow cells.
Timepoint [1] 0 0
From baseline up to approximately 24 months
Secondary outcome [2] 0 0
Percent of Participants Who Achieve VGPR or Better - Very Good Partial Response (VGPR) per international myeloma working group (IMWG) criteria is defined as serum or urine myeloma protein (m-protein) detectable by immunofixation but not on electrophoresis, or greater than or equal to 90% reduction in serum m-protein and urine m-protein less than 100 mg/24 hours.
Timepoint [2] 0 0
From baseline up to approximately 24 months
Secondary outcome [3] 0 0
Overall Response Rate (ORR) - ORR is described as the percentage of participants who experience partial response (PR) or better; PR per IMWG is described as follows:
= 50% reduction of serum M-protein and reduction in 24-hour urinary M protein by = 90% or to < 200 mg/24 h
If the serum and urine M-protein are not measurable, a decrease = 50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria
If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, = 50% reduction in bone marrow plasma cells is required in place of M-protein, provided baseline percentage was = 30%
In addition, if present at baseline, = 50% reduction in size of soft tissue plasmacytomas is also required
Timepoint [3] 0 0
From baseline up to approximately 24 months
Secondary outcome [4] 0 0
Time to Response (TTR) - Time to response is defined as the time from randomization to the first response (CR, stringent complete response [sCR], VGPR, PR).
Timepoint [4] 0 0
From baseline up to approximately 24 months
Secondary outcome [5] 0 0
Duration of response (DOR) - DOR is defined as the time from first observation of PR to the time of disease progression, with deaths from causes other than progression censored.
Timepoint [5] 0 0
Approximately 7 years
Secondary outcome [6] 0 0
Progression-free Survival (PFS) - PFS is defined as time from start of the treatment to disease progression or death (regardless of cause of death), whichever comes first.
Timepoint [6] 0 0
Approximately 7 years
Secondary outcome [7] 0 0
Minimal Residual Disease (MRD) Negativity Rate at 12 Months - Percent of participants meeting the MRD Negative criteria at 12 months after initial dose; MRD Negative defined as less than one myeloma cell per 100,000 bone marrow cells.
Timepoint [7] 0 0
Approximately 12 months after initial dose of study drug
Secondary outcome [8] 0 0
Time to Disease Progression (TTP) - TTP is defined as the time from start of treatment to disease progression, with deaths from causes other than progression censored.
Timepoint [8] 0 0
Approximately 7 years
Secondary outcome [9] 0 0
Time to Next Treatment (TTNT) - The time to next treatment is defined as the time between the date of the first study drug intake and the date of the first next treatment intake after study drug discontinuation.
Timepoint [9] 0 0
Approximately 7 years
Secondary outcome [10] 0 0
Overall Survival (OS) Rate - OS was defined as the time from the date the participant was randomized to the date of death.
Timepoint [10] 0 0
Approximately 7 years

Eligibility
Key inclusion criteria
- Must have documented, confirmed active multiple myeloma (MM) with greater than or
equal to 10% clonal bone marrow plasma cells or biopsy-proven bone or extramedullary
plasmacytoma and any one or more of the following myeloma-defining events:

- Evidence of end organ damage attributed to the underlying plasma cell
proliferative disorder and satisfying at least one of the protocol specified
laboratory criteria for calcium elevation, renal failure, anemia, or lytic bone
lesions; OR

- One or more of the biomarkers of malignancy as described in the protocol.

- Must have MM positive for the t(11;14) translocation, as determined by methods
described in the protocol.

- Must have measurable disease defined by at least one of the following criteria:

- Serum M-protein = 1.0 g/dL (immunoglobulin [Ig]G myeloma) or greater than or
equal to 0.5 g/dL (IgA, IgM, IgD, or IgE myeloma);

- Urine M-protein greater than or equal to 200 mg/24 hours;

- Serum free light chain (FLC) greater than or equal to 10 mg/dL (100 mg/L)
provided serum FLC ratio is abnormal.

- Newly diagnosed and not considered a candidate for high-dose therapy and hematopoietic
stem cell transplantation (HSCT)

- Must have Eastern Cooperative Oncology Group performance status less than or equal to
2.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has a co-existing condition as specified in the protocol.

- Has history of other active malignancies, including myelodysplastic syndromes (MDS)
within the past 3 years with specific exceptions detailed in the protocol.

- Has been treated with or received any of the following:

- Prior or current systemic therapy or hematopoietic stem cell transplantation
(HSCT) for MM (a short course of treatment with corticosteroids equivalent to
dexamethasone 40 mg/day for a maximum of 4 days is allowed before treatment); use
of systemic strong or moderate inhibitor or inducer of cytochrome P450(CYP)3A
within 7 days before the first dose of study drug.

- Radiation therapy within 2 weeks of dosing

- Plasmapheresis within 4 weeks of dosing

- Immunization with live vaccine within 8 weeks of dosing

- Has a contraindication or inability to comply with antithrombotic prophylaxis.

Study design
Purpose of the study
Treatment
Allocation to intervention
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)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
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,VIC
Recruitment hospital [1] 0 0
Westmead Hospital /ID# 210267 - Westmead
Recruitment hospital [2] 0 0
St. Vincents Hosp Melbourne /ID# 210266 - Fitzroy
Recruitment hospital [3] 0 0
Austin Hospital /ID# 210268 - Heidelberg
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Wisconsin
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
Spain
State/province [9] 0 0
Navarra, Comunidad
Country [10] 0 0
Spain
State/province [10] 0 0
Barcelona
Country [11] 0 0
Spain
State/province [11] 0 0
Madrid
Country [12] 0 0
Spain
State/province [12] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Celgene Corporation
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the safety and preliminary efficacy of venetoclax when combined with
lenalidomide and dexamethasone for participants with newly diagnosed, active t(11;14)
positive multiple myeloma (MM).

This study will consist of 2 parts: Part 1 Dose Escalation and Part 2 Dose Expansion.
Trial website
https://clinicaltrials.gov/show/NCT03785184
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
847.283.8955
Fax 0 0
Email 0 0
abbvieclinicaltrials@abbvie.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable