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Proteasome Inhibitor

Combination Therapy for Multiple Myeloma

Q: What is the main purpose of this research project?

<p>Janssen Research &#x26; Development, LLC, the sponsor of this trial, has specified that the primary outcome-- which will be observed over a period of 3.5 years post-enrolment-- is Overall Survival (OS). Additionally, this study will measure Tmax of Venetoclax, Cmax of Venetoclax, and Minimal Residual Disease (MRD) as secondary outcomes.</p>

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

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

Study 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.Check my eligibility

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.See study design

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.

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

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Complete Response (CR) or Better Rate

Duration of Response (DOR)

Overall Response Rate (ORR)

+5 more

Secondary outcome measures

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%

Neutrophil count decreased

11%

Blood creatinine increased

11%

Hypokalaemia

11%

Dermatitis

11%

Pneumonia pseudomonal

11%

Rhinovirus infection

11%

White blood cell count decreased

11%

Pneumonia

11%

Abdominal pain

11%

Anaemia

11%

Sepsis

11%

Gastroenteritis

11%

SARS-CoV-2 test positive

11%

Electrocardiogram QT prolonged

11%

Febrile neutropenia

11%

COVID-19

11%

Supraventricular tachycardia

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

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

~1860

Venetoclax

2019

Completed Phase 3

~1990

Bortezomib

2005

Completed Phase 2

~1140

Dexamethasone

2007

Completed Phase 4

~2590

0 / 6Eligibility criteria met

Find a Location

Who is running the clinical trial?

Janssen Research & Development, LLCIndustry Sponsor

975 Previous Clinical Trials

6,384,152 Total Patients Enrolled

70 Trials studying Multiple Myeloma

19,261 Patients Enrolled for Multiple Myeloma

AbbVieLead Sponsor

954 Previous Clinical Trials

500,888 Total Patients Enrolled

34 Trials studying Multiple Myeloma

5,235 Patients Enrolled for Multiple Myeloma

ABBVIE INC.Study DirectorAbbVie

394 Previous Clinical Trials

145,722 Total Patients Enrolled

14 Trials studying Multiple Myeloma

2,331 Patients Enrolled for Multiple Myeloma

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

For what purpose is Venetoclax most often given to patients?

"Venetoclax is most frequently used to treat ophthalmia, sympathetic. However, it has also been shown to ameliorate branch retinal vein occlusion, macular edema, and communicable diseases."

Answered by AI

Are we still able to enroll new participants in this study?

"This trial is not recruiting at this time, though it was last updated on March 2nd, 2022. There are 827 other clinical trials for multiple myeloma and 886 for Venetoclax that are currently looking for patients."

Answered by AI

What is the FDA's opinion of Venetoclax?

"While there is some evidence to support Venetoclax's safety, it only received a score of 2 because this is a phase 2 trial and no efficacy data has been collected yet."

Answered by AI

Are there any other ongoing investigations with Venetoclax?

"Venetoclax was investigated for the first time in 2002 by Manitoba Blood & Marrow Transplant Program CancerCare Manitoba. So far, 886 studies are still recruiting participants, with a large number of these trials based in Hackensack, New jersey. In total, there have been 1453 completed venetoclax studies as of now."

Answered by AI

Could you please list how many hospitals are enrolled in this research project?

"So far, Hackensack Univ Med Ctr /ID# 225111 in Hackensack, Royal Victoria Hospital / McGill University Health Centre /ID# 167824 in Chicago, and The University of Chicago Medical Center /ID# 165429 in Boston have recruited 14 patients for this study with other locations expected to follow suit."

Answered by AI

What is the main purpose of this research project?

"Janssen Research & Development, LLC, the sponsor of this trial, has specified that the primary outcome-- which will be observed over a period of 3.5 years post-enrolment-- is Overall Survival (OS). Additionally, this study will measure Tmax of Venetoclax, Cmax of Venetoclax, and Minimal Residual Disease (MRD) as secondary outcomes."

Answered by AI

Recent research and studies

Journal of Clinical OncologyJournal

Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, with or Without Bortezomib, in Patients with Relapsed or Refractory Multiple Myeloma with and Without T(11;14)

Bahlis, Nizar J., Rachid Baz, Simon J. Harrison, Hang Quach, Shir-Jing Ho, Annette Juul Vangsted, Torben Plesner, et al.. 2021. “Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, with or Without Bortezomib, in Patients with Relapsed or Refractory Multiple Myeloma with and Without T(11;14)”. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). doi:10.1200/jco.21.00443.

clinicaltrials.govStudy

A Study of Combination Therapy With Venetoclax, Daratumumab and Dexamethasone (With and Without Bortezomib) in Participants With Relapsed or Refractory Multiple Myeloma

2018. "A Study of Combination Therapy With Venetoclax, Daratumumab and Dexamethasone (With and Without Bortezomib) in Participants With Relapsed or Refractory Multiple Myeloma". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03314181.

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