Combination Therapy for Multiple Myeloma

Recruiting in Palo Alto (17 mi)

+47 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: AbbVie

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?This is a study of venetoclax, daratumumab, and dexamethasone with and without bortezomib combination therapy to evaluate safety, tolerability, and efficacy of these combinations in participants with relapsed or refractory multiple myeloma. The study will consist of 3 distinct parts: Part 1 includes participants with t(11;14) positive relapsed/refractory (R/R) multiple myeloma who will receive venetoclax in combination with daratumumab and dexamethasone (VenDd); Part 2 includes participants with R/R multiple myeloma who will receive venetoclax in combination with daratumumab, bortezomib, and dexamethasone (VenDVd); Part 3 includes participants with t(11;14) positive R/R multiple myeloma who will receive venetoclax in combination with daratumumab and dexamethasone (VenDd) or daratumumab, bortezomib, and dexamethasone (DVd). Part 1 and Part 2 are non-randomized and will be initiated with a dose-escalation phase in which increasing doses of venetoclax will be given with fixed doses of daratumumab and dexamethasone (Part 1a) or with fixed doses of daratumumab, bortezomib, and dexamethasone (Part 2a). Each dose escalation phase will be followed by a single-arm, open-label expansion phase. Part 3 will include a randomized, open-label expansion phase with participants receiving venetoclax in combination with daratumumab and dexamethasone (VenDd) or daratumumab, bortezomib, and dexamethasone (DVd).

Eligibility Criteria

This trial is for adults with relapsed or refractory multiple myeloma, specifically those who have measurable disease and have undergone previous treatments. Participants must be t(11;14) positive for certain parts of the study and should have good blood, kidney, and liver function. People with recent high-dose steroid use, central nervous system involvement by myeloma, significant medical conditions, other active cancers in the last 3 years (with exceptions), allergies to study drugs or their components, prior BCL-2 inhibitor or anti-CD38 therapy (for some parts), or active COVID-19 are excluded.

Inclusion Criteria

My cancer can be measured by specific blood or urine tests.

My multiple myeloma has worsened or not responded to my last treatment.

My bone marrow samples have been collected.

+4 more

Exclusion Criteria

I have taken corticosteroids in the last 2 weeks.

I have been treated with venetoclax or a similar drug before.

I have been treated with daratumumab or another anti-CD38 therapy.

+9 more

Participant Groups

The trial tests combinations of venetoclax with daratumumab and dexamethasone—with or without bortezomib—to assess safety and effectiveness in treating multiple myeloma that has come back or hasn't responded to treatment. It's divided into three parts: two non-randomized phases exploring different drug combos at increasing doses followed by an expansion phase; the third part randomly assigns patients to one of two treatment groups.

7Treatment groups

Experimental Treatment

Active Control

Group I: Arm G: VenDd Dose ExpansionExperimental Treatment3 Interventions

Venetoclax at a pre-determined dose, administered orally QD in combination with daratumumab (1800 mg subcutaneous injection (preferred) or 16 mg/kg IV) administered in accordance with prescribing information and dexamethasone (oral or IV) 40 mg weekly (or 20 mg weekly, if necessary, as described in the protocol).

Group II: Arm F: VenDd Dose ExpansionExperimental Treatment3 Interventions

Group III: Arm E, Part 2b: VenDVd Dose ExpansionExperimental Treatment4 Interventions

Venetoclax at dose determined by the dose-escalation phase, administered orally QD in combination with daratumumab (1800 mg subcutaneous injection (preferred) or 16 mg/kg IV) administered in accordance with prescribing information, bortezomib (1.3 mg/m2 subcutaneous injection) Cycles 1-8, Days 1, 4, 8 and 11, and dexamethasone (oral or IV) 20 mg Cycles 1 - 3, Days 1, 2, 4, 5, 8, 9, 11,12 and 15; 20 mg Cycles 4-8, Days 1,2,4,5,8,9,11 and 12; 40 mg weekly (or 20 mg weekly, if necessary as described in the protocol) Cycle 9+.

Group IV: Arm D, Part 2a: VenDVd Dose EscalationExperimental Treatment4 Interventions

Venetoclax at various doses administered orally QD in combination with daratumumab (1800 mg subcutaneous injection (preferred) or 16 mg/kg IV) administered in accordance with prescribing information, bortezomib (1.3 mg/m2 subcutaneous injection \[preferred\] or IV) Cycles 1-8, Days 1, 4, 8 and 11), and dexamethasone (oral or IV) 20 mg Cycles 1 - 3, Days 1, 2, 4, 5, 8, 9, 11,12 and 15; 20 mg Cycles 4-8, Days 1,2,4,5,8,9,11 and 12; 40 mg weekly (or 20 mg weekly, if necessary as described in the protocol) Cycle 9+.

Group V: Arm B, Part 1b: VenDd Dose ExpansionExperimental Treatment3 Interventions

Venetoclax at a dose determined by the dose-escalation phase, administered orally QD in combination with daratumumab (1800 mg subcutaneous injection (preferred) or 16 mg/kg IV) administered in accordance with prescribing information and dexamethasone (oral or IV) 40 mg weekly (or 20 mg weekly, if necessary, as described in the protocol).

Group VI: Arm A, Part 1a: VenDd Dose EscalationExperimental Treatment3 Interventions

Venetoclax (Ven) various doses administered orally, once daily (QD) in combination with daratumumab (D) (1800 mg subcutaneous injection (preferred) or 16 mg/kg intravenous \[IV\]) administered in accordance with prescribing information and dexamethasone (d) (oral or IV) 40 mg weekly (or 20 mg weekly, if necessary, as described in the protocol).

Group VII: Arm H: DVd DoseActive Control3 Interventions

Daratumumab (1800 mg subcutaneous injection (preferred) or 16 mg/kg IV) administered in accordance with prescribing information, bortezomib (1.3 mg/m2 subcutaneous injection) Cycles 1-8: Days 1, 4, 8 and 11, and dexamethasone (oral or IV) 20 mg on Cycles 1 - 3: Days 1, 2, 4, 5, 8, 9, 11,12 and 15; 40 mg weekly (or 20 mg weekly, if necessary as described in the protocol) on Cycles 4-8: Days 1,2,4,5,8,9,11 and 12; 20 mg monthly for Cycles 9+: Day 1

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Velcade for: