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Proteasome Inhibitor

Combination Therapy for Multiple Myeloma

Phase 2

Waitlist Available

Research Sponsored by AbbVie

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant has relapsed or refractory multiple myeloma with documented evidence of progression that occurred during or after the participant's last treatment regimen based on investigator's determination of International Myeloma Working Group (IMWG) criteria

Measurable disease confirmed by central lab at Screening, defined by at least 1 of the following: Serum M-protein >= 1.0 g/dL (>= 10 g/L), OR Urine M-protein >= 200 mg/24 hours, OR Serum free light chain (FLC) >= 10 mg/dL, provided serum FLC ratio is abnormal in participants who do not have measurable disease by Serum Protein Electrophoresis (SPEP) or Urine Protein Electrophoresis (UPEP) criteria

Must not have

Previous treatment with venetoclax or other B-Cell Lymphoma 2 (BCL-2) inhibitor

Previous treatment with daratumumab or other anti-CD38 therapy for participants in Parts 1 and 2

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 12 months after confirmation of complete response (cr) or stringent complete response (scr)

Awards & highlights

No Placebo-Only Group

Summary

This trial is studying a combination of drugs as a potential treatment for relapsed or refractory multiple myeloma. The drugs involved are venetoclax, daratumumab, dexamethasone, and bortezomib. The study will consist of three parts, with each part investigating a different combination of drugs. The first two parts are non-randomized, while the third part is randomized.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include nausea, diarrhea, low blood cell counts leading to increased infection risk or bleeding problems, fatigue, nerve damage causing numbness or pain (from bortezomib), allergic reactions during infusion of monoclonal antibodies like daratumumab. Each patient may experience side effects differently.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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My bone marrow samples have been collected.

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My cancer is t(11;14) positive according to a specific lab test.

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I can take care of myself but might not be able to do heavy physical work.

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My blood, kidney, and liver functions are all within normal ranges.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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My condition did not improve after proteasome inhibitor treatment.

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My multiple myeloma has spread to my brain.

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I currently have an active severe COVID-19 infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 12 months after confirmation of complete response (cr) or stringent complete response (scr)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 12 months after confirmation of complete response (cr) or stringent complete response (scr)

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 12 months after confirmation of complete response (cr) or stringent complete response (scr) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Complete Response (CR) or Better Rate

Duration of Response (DOR)

Overall Response Rate (ORR)

+5 more

Secondary study objectives

AUC0-24 of Venetoclax

Cmax of Venetoclax

Minimal Residual Disease (MRD)

+1 more

Side effects data

From 2022 Phase 3 trial • 389 Patients • NCT02005471

33%

Neutropenia

11%

SARS-CoV-2 test positive

11%

Sepsis

11%

Abdominal pain

11%

Pneumonia

11%

Rhinovirus infection

11%

COVID-19

11%

Gastroenteritis

11%

Pneumonia pseudomonal

11%

Electrocardiogram QT prolonged

11%

Anaemia

11%

Neutrophil count decreased

11%

Hypokalaemia

11%

Febrile neutropenia

11%

Supraventricular tachycardia

11%

Blood creatinine increased

11%

White blood cell count decreased

11%

Dermatitis

100%

80%

60%

40%

20%

Study treatment Arm

Bendamustine + Rituximab Crossover Substudy

Venetoclax + Rituximab Re-Treatment Substudy

Venetoclax + Rituximab Main Study

Bendamustine + Rituximab Main Study

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Daratumumab

2014

Completed Phase 3

~2380

Venetoclax

2019

Completed Phase 3

~2240