Clinical trial NCT02951117: 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
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: lymphoid malignancies
Next generation sequencing
Refractory Multiple Myeloma
Relapsed Multiple Myeloma
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-11-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of venetoclax and ABBV-838 combination therapy when administered with dexamethasone
timeFrame: Minimum first cycle of dosing (21 or 28 days, depending on arm)
measure: Number of participants with adverse events
timeFrame: Up to approximately 2 years following the first dose of the last subject enrolled
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax) of venetoclax
timeFrame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
measure: Time to Cmax (Tmax) of venetoclax
timeFrame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
measure: Area under the plasma concentration-time curve over the 24-hour dose interval (AUC0-24) of venetoclax
timeFrame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
measure: Objective Response Rate (ORR)
timeFrame: 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
measure: Cmax of ABBV-838
timeFrame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
measure: Tmax of ABBV-838
timeFrame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
measure: AUC over the dose interval (AUC0-τ) of ABBV-838
timeFrame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
measure: Total monoclonal anti-CS1 antibody (total mAb)
timeFrame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
measure: Monomethyl auristatin E (MMAE) toxin levels
timeFrame: Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively)
measure: Minimal Residual Disease (MRD)
timeFrame: Cycle 4 Day 1 and treatment completion (up to 2 years following the first dose of the last subject enrolled)
measure: Terminal phase elimination rate constant (β) for ABBV-838
timeFrame: Cycle 1 Day 1
measure: Terminal elimination half-life (t1/2) for ABBV-838
timeFrame: Cycle 1 Day 1
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: St Vincent´s Hospital /ID# 153022
city: Fitzroy
country: Australia
facility: St. Vincents Hospital Melbourne /ID# 157925
city: Prahran
country: Australia
facility: The Alfred Hospital /ID# 150202
Study officials:
affiliation: AbbVie
name: Orlando Bueno, MD
role: STUDY_DIRECTOR
References: