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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

Primary Purpose

Multiple Myeloma

Status

Withdrawn

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

Venetoclax

ABBV-838

Dexamethasone

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring lymphoid malignancies, Next generation sequencing, Refractory Multiple Myeloma, Relapsed Multiple Myeloma

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

St Vincent´s Hospital /ID# 153022
St. Vincents Hospital Melbourne /ID# 157925
The Alfred Hospital /ID# 150202

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm A Venetoclax QD + ABBV-838 Q3W + Dexamethasone

Arm B Venetoclax QD + ABBV-838 Q1W or Q2W + Dexamethasone Q1W

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Number of participants with adverse events

Secondary Outcome Measures

Maximum observed plasma concentration (Cmax) of venetoclax

Time to Cmax (Tmax) of venetoclax

Area under the plasma concentration-time curve over the 24-hour dose interval (AUC0-24) of venetoclax

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.

Cmax of ABBV-838

Tmax of ABBV-838

AUC over the dose interval (AUC0-τ) of ABBV-838

Total monoclonal anti-CS1 antibody (total mAb)

Monomethyl auristatin E (MMAE) toxin levels

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.

Terminal phase elimination rate constant (β) for ABBV-838

Terminal elimination half-life (t1/2) for ABBV-838

Full Information

NCT ID

NCT02951117

First Posted

October 28, 2016

Last Updated

June 1, 2017

Sponsor

AbbVie

1. Study Identification

Unique Protocol Identification Number

NCT02951117

Brief 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

Official 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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Withdrawn

Why Stopped

No participants enrolled

Study Start Date

August 31, 2017 (Anticipated)

Primary Completion Date

July 28, 2020 (Anticipated)

Study Completion Date

April 28, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AbbVie

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

lymphoid malignancies, Next generation sequencing, Refractory Multiple Myeloma, Relapsed Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A Venetoclax QD + ABBV-838 Q3W + Dexamethasone

Arm Type

Experimental

Arm Description

Arm Title

Arm B Venetoclax QD + ABBV-838 Q1W or Q2W + Dexamethasone Q1W

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Venetoclax

Other Intervention Name(s)

ABT-199

Intervention Description

Tablet

Intervention Type

Drug

Intervention Name(s)

ABBV-838

Intervention Description

Intravenous infusion

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

Tablet or intravenous infusion

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of venetoclax and ABBV-838 combination therapy when administered with dexamethasone

Description

Time Frame

Minimum first cycle of dosing (21 or 28 days, depending on arm)

Title

Number of participants with adverse events

Time Frame

Up to approximately 2 years following the first dose of the last subject enrolled

Secondary Outcome Measure Information:

Title

Maximum observed plasma concentration (Cmax) of venetoclax

Time Frame

Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

Title

Time to Cmax (Tmax) of venetoclax

Time Frame

Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

Title

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)

Title

Objective Response Rate (ORR)

Description

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

Title

Cmax of ABBV-838

Time Frame

Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

Title

Tmax of ABBV-838

Time Frame

Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

Title

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)

Title

Total monoclonal anti-CS1 antibody (total mAb)

Time Frame

Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

Title

Monomethyl auristatin E (MMAE) toxin levels

Time Frame

Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)

Title

Minimal Residual Disease (MRD)

Description

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.

Time Frame

Cycle 4 Day 1 and treatment completion (up to 2 years following the first dose of the last subject enrolled)

Title

Terminal phase elimination rate constant (β) for ABBV-838

Time Frame

Cycle 1 Day 1

Title

Terminal elimination half-life (t1/2) for ABBV-838

Time Frame

Cycle 1 Day 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Orlando Bueno, MD

Organizational Affiliation

AbbVie

Official's Role

Study Director

Facility Information:

Facility Name

St Vincent´s Hospital /ID# 153022

City

Darlinghurst

ZIP/Postal Code

2010

Country

Australia

Facility Name

St. Vincents Hospital Melbourne /ID# 157925

City

Fitzroy

ZIP/Postal Code

3065

Country

Australia

Facility Name

The Alfred Hospital /ID# 150202

City

Prahran

ZIP/Postal Code

3181

Country

Australia

12. IPD Sharing Statement

Learn more about this trial

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

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