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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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)
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)
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
Sex
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
31/08/2017
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/04/2021
Actual
Sample size
Target
Accrual to date
Final
0
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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT02951117