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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02951117
• Other study ID #: M15-655
• Secondary ID: 2016-001300-28
• Status: Withdrawn
• Phase: Phase 1
• First received: October 28, 2016
• Last updated: June 1, 2017
• Start date: August 31, 2017
• Est. completion date: April 28, 2021

Study information

• Verified date: June 2017
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 28, 2021
• Est. primary completion date: July 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Venetoclax
Tablet
• ABBV-838
Intravenous infusion
• Dexamethasone
Tablet or intravenous infusion

Locations

Country	Name	City	State
Australia	St Vincent´s Hospital /ID# 153022	Darlinghurst
Australia	St. Vincents Hospital Melbourne /ID# 157925	Fitzroy
Australia	The Alfred Hospital /ID# 150202	Prahran

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Minimum first cycle of dosing (21 or 28 days, depending on arm)
Primary	Number of participants with adverse events		Up to approximately 2 years following the first dose of the last subject enrolled
Secondary	Maximum observed plasma concentration (Cmax) of venetoclax		Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary	Time to Cmax (Tmax) of venetoclax		Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary	Area under the plasma concentration-time curve over the 24-hour dose interval (AUC0-24) of venetoclax		Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary	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.	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	Cmax of ABBV-838		Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary	Tmax of ABBV-838		Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary	AUC over the dose interval (AUC0-t) of ABBV-838		Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary	Total monoclonal anti-CS1 antibody (total mAb)		Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary	Monomethyl auristatin E (MMAE) toxin levels		Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
Secondary	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.	Cycle 4 Day 1 and treatment completion (up to 2 years following the first dose of the last subject enrolled)
Secondary	Terminal phase elimination rate constant (ß) for ABBV-838		Cycle 1 Day 1
Secondary	Terminal elimination half-life (t1/2) for ABBV-838		Cycle 1 Day 1