Multiple Myeloma
Conditions
Keywords
lymphoid malignancies, Next generation sequencing, Refractory Multiple Myeloma, Relapsed 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.
Interventions
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD), and recommended phase two dose (RPTD) of venetoclax and ABBV-838 combination therapy when administered with dexamethasone | 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 | Up to approximately 2 years following the first dose of the last subject enrolled | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| Objective Response Rate (ORR) | 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 | Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) | — |
| Tmax of ABBV-838 | Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) | — |
| AUC over the dose interval (AUC0-τ) of ABBV-838 | Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) | — |
| Maximum observed plasma concentration (Cmax) of venetoclax | Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) | — |
| Monomethyl auristatin E (MMAE) toxin levels | Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) | — |
| Minimal Residual Disease (MRD) | 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 | Cycle 1 Day 1 | — |
| Terminal elimination half-life (t1/2) for ABBV-838 | Cycle 1 Day 1 | — |
| Total monoclonal anti-CS1 antibody (total mAb) | Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) | — |
| Time to Cmax (Tmax) of venetoclax | Approximately 43 or 57 days (Treatment Arm A and Treatment Arm B, respectively) | — |
Countries
Australia
Outcome results
None listed