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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02951117




Registration number
NCT02951117
Ethics application status
Date submitted
28/10/2016
Date registered
1/11/2016
Date last updated
5/06/2017

Titles & IDs
Public title
A Study of Venetoclax and ABBV-838 Combination Therapy With Dexamethasone in Participants With Multiple Myeloma Whose Cancer Has Come Back or Had No Response to Recent Cancer Treatment
Scientific title
A Phase 1b, Open Label, Multicenter, Dose Escalation Study of Venetoclax and ABBV-838 Combination Therapy With Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Secondary ID [1] 0 0
2016-001300-28
Secondary ID [2] 0 0
M15-655
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 - ABBV-838
Treatment: Drugs - Dexamethasone

Experimental: Arm A Venetoclax QD + ABBV-838 Q3W + Dexamethasone - ABBV-838 administered at cohort-defined doses every 3 weeks (Q3W; starting dose 4.0 mg/kg) in combination with venetoclax (400 mg or 800 mg once daily [QD]) and dexamethasone (40 mg once weekly [Q1W]); once the maximum-tolerated-dose (MTD) and recommended phase two dose (RPTD) are determined, ABBV-838 in combination with venetoclax and dexamethasone at RPTD will be administered in a dose expansion phase of the study.

Experimental: Arm B Venetoclax QD + ABBV-838 Q1W or Q2W + Dexamethasone Q1W - Dose escalation portion will investigate either the ABBV-838 weekly (Q1W) or bi-weekly (Q2W) dosing interval in combination with venetoclax (400 or 800 mg QD) and dexamethasone (40 mg Q1W).
The dose expansion portion will investigate either the ABBV-838 weekly (Q1W) or bi-weekly (Q2W) dosing interval in combination with venetoclax and dexamethasone at the RPTD combination defined from the Dose Escalation portion.


Treatment: Drugs: Venetoclax
Tablet

Treatment: Drugs: ABBV-838
Intravenous infusion

Treatment: Drugs: Dexamethasone
Tablet or intravenous infusion

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

Outcomes
Primary outcome [1] 0 0
Maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of venetoclax and ABBV-838 combination therapy when administered with dexamethasone - The MTD and the RPTD of venetoclax and ABBV-838 combination therapy with dexamethasone will be determined during the dose escalation phase of the study. Once the RPTD combination has been determined, the dose expansion portion will begin.
Timepoint [1] 0 0
Minimum first cycle of dosing (21 or 28 days, depending on arm)
Primary outcome [2] 0 0
Number of participants with adverse events
Timepoint [2] 0 0
Up to approximately 2 years following the first dose of the last subject enrolled
Secondary outcome [1] 0 0
Maximum observed plasma concentration (Cmax) of venetoclax
Timepoint [1] 0 0
Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary outcome [2] 0 0
Time to Cmax (Tmax) of venetoclax
Timepoint [2] 0 0
Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary outcome [3] 0 0
Area under the plasma concentration-time curve over the 24-hour dose interval (AUC0-24) of venetoclax
Timepoint [3] 0 0
Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary outcome [4] 0 0
Objective Response Rate (ORR) - The Objective Response Rate (ORR) is defined as the proportion of subjects with a response (Stringent Complete Response [sCR], Complete Response [CR], Very Good Partial Response [VGPR] or Partial Response [PR]) based on the International Myeloma Working Group (IMWG) criteria.
Timepoint [4] 0 0
Cycle 2 Day 1 and Day 1 of every cycle thereafter for up to 2 years following the first dose of the last subject enrolled
Secondary outcome [5] 0 0
Cmax of ABBV-838
Timepoint [5] 0 0
Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary outcome [6] 0 0
Tmax of ABBV-838
Timepoint [6] 0 0
Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary outcome [7] 0 0
AUC over the dose interval (AUC0-t) of ABBV-838
Timepoint [7] 0 0
Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary outcome [8] 0 0
Total monoclonal anti-CS1 antibody (total mAb)
Timepoint [8] 0 0
Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary outcome [9] 0 0
Monomethyl auristatin E (MMAE) toxin levels
Timepoint [9] 0 0
Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary outcome [10] 0 0
Minimal Residual Disease (MRD) - MRD will be assessed in the bone marrow by next generation sequencing (NGS). MRD negativity in bone marrow aspirates will be defined at 10-5 threshold as assessed by NGS.
Timepoint [10] 0 0
Cycle 4 Day 1 and treatment completion (up to 2 years following the first dose of the last subject enrolled)
Secondary outcome [11] 0 0
Terminal phase elimination rate constant (ß) for ABBV-838
Timepoint [11] 0 0
Cycle 1 Day 1
Secondary outcome [12] 0 0
Terminal elimination half-life (t1/2) for ABBV-838
Timepoint [12] 0 0
Cycle 1 Day 1

Eligibility
Key inclusion criteria
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
for participants in the dose escalation portion of the study and ECOG less than or
equal to 2 in the dose expansion portion.

- Received at least 2 prior therapies including an Immunomodulatory Thalidomide
Derivative Compounds (IMiD) and a proteasome inhibitor.

- Documented relapsed or progressive multiple myeloma on or after any regimen or is
refractory to the most recent line of therapy.

- Received at least 2 prior therapies including an IMiD and a proteasome inhibitor.

- Documented relapsed or progressive multiple myeloma on or after any regimen or is
refractory to the most recent line of therapy.

- Eligible for and agree to bone marrow (BM) aspirate prior to treatment start and at
designated times per protocol.

- Measurable disease at Screening, defined as at least one of the following M component
in serum (greater than or equal to 0.5 g/dL) and/or urine (greater than or equal to
0.2 g excreted in a 24 hour collection sample) or serum free light chain greater than
or equal to 100 mg/dL with an abnormal ?/? ratio of less than 0.26 or greater than
1.65.
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Received any anti-myeloma therapy (other than monoclonal antibodies), including
chemotherapy, radiotherapy, biological, immunotherapy or an investigational therapy,
including targeted small molecule agents within 5 half-lives (or 14 days if half-live
unknown) prior to first dose of first dose of venetoclax, ABBV-838, and dexamethasone.

- Received anti-myeloma monoclonal antibodies within 6 weeks prior to first dose of
venetoclax, ABBV-838, and dexamethasone.

- Has a significant history of renal, neurologic (peripheral neuropathy), psychiatric,
endocrinologic (diabetes mellitus), metabolic, immunologic, cardiovascular, pulmonary
or hepatic disease within the last 6 months.

- Received corticosteroid therapy at a dose equivalent to greater than or equal to 4
mg/day of dexamethasone within 3 weeks prior to first dose.

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 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
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)
Recruitment hospital [1] 0 0
St Vincent´s Hospital /ID# 153022 - Darlinghurst
Recruitment hospital [2] 0 0
St. Vincents Hospital Melbourne /ID# 157925 - Fitzroy
Recruitment hospital [3] 0 0
The Alfred Hospital /ID# 150202 - Prahran
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
3181 - Prahran

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is an open-label, multicenter clinical trial designed to evaluate the safety and
potential efficacy of venetoclax and ABBV-838 combination therapy with dexamethasone in
participants with relapsed or refractory multiple myeloma (MM) who have received 2 or more
prior lines of therapy for multiple myeloma (MM). The study will consist of 2 arms: Arm A and
Arm B (if applicable). Each arm will have a dose escalation and dose expansion portion.
Trial website
https://clinicaltrials.gov/show/NCT02951117
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Orlando Bueno, MD
Address 0 0
AbbVie
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
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02951117