Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02951117
Recruitment Status : Withdrawn (No participants enrolled)
First Posted : November 1, 2016
Last Update Posted : June 5, 2017
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE October 28, 2016
First Posted Date  ICMJE November 1, 2016
Last Update Posted Date June 5, 2017
Estimated Study Start Date  ICMJE August 31, 2017
Estimated Primary Completion Date July 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2016)
  • Maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of venetoclax and ABBV-838 combination therapy when administered with dexamethasone [ Time Frame: Minimum first cycle of dosing (21 or 28 days, depending on arm) ]
    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.
  • Number of participants with adverse events [ Time Frame: Up to approximately 2 years following the first dose of the last subject enrolled ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02951117 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2016)
  • Maximum observed plasma concentration (Cmax) of venetoclax [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  • Time to Cmax (Tmax) of venetoclax [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  • Area under the plasma concentration-time curve over the 24-hour dose interval (AUC0-24) of venetoclax [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  • Objective Response Rate (ORR) [ Time Frame: 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 ]
    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.
  • Cmax of ABBV-838 [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  • Tmax of ABBV-838 [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  • AUC over the dose interval (AUC0-τ) of ABBV-838 [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  • Total monoclonal anti-CS1 antibody (total mAb) [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  • Monomethyl auristatin E (MMAE) toxin levels [ Time Frame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) ]
  • Minimal Residual Disease (MRD) [ Time Frame: Cycle 4 Day 1 and treatment completion (up to 2 years following the first dose of the last subject enrolled) ]
    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.
  • Terminal phase elimination rate constant (β) for ABBV-838 [ Time Frame: Cycle 1 Day 1 ]
  • Terminal elimination half-life (t1/2) for ABBV-838 [ Time Frame: Cycle 1 Day 1 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
Detailed Description

The study will consist of 2 arms: Arm A and Arm B (if applicable). Arm A dose escalation will investigate up to 3 doses of ABBV-838 at 3-week dosing intervals (Q3W) in combination with venetoclax and dexamethasone. Arm A dose expansion portion will investigate the ABBV-838 Q3W dosing interval with venetoclax and dexamethasone at the recommended phase two dose (RPTD) combination defined from the Dose Escalation portion.

Based on data from the ongoing ABBV-838 monotherapy study (Study M14-467) Arm B dose escalation may be conducted, if deemed necessary. If conducted, Arm B dose excalation will investigate up to 3 doses of ABBV-838 at either weekly (Q1W) or bi-weekly (Q2W) dosing intervals in combination with venetoclax and dexamethasone. Arm B dose expansion portion will investigate either the ABBV-838 Q1W or Q2W dosing interval in combination with venetoclax and dexamethasone at the RPTD combination defined from the Dose Escalation portion.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Venetoclax
    Tablet
    Other Name: ABT-199
  • Drug: ABBV-838
    Intravenous infusion
  • Drug: Dexamethasone
    Tablet or intravenous infusion
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Venetoclax
    • Drug: ABBV-838
    • Drug: Dexamethasone
  • 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.

    Interventions:
    • Drug: Venetoclax
    • Drug: ABBV-838
    • Drug: Dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: June 1, 2017)
0
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2016)
70
Estimated Study Completion Date  ICMJE April 28, 2021
Estimated Primary Completion Date July 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 κ/λ ratio of less than 0.26 or greater than 1.65.

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02951117
Other Study ID Numbers  ICMJE M15-655
2016-001300-28 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Orlando Bueno, MD AbbVie
PRS Account AbbVie
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP