Venetoclax + Dexamethasone vs Pomalidomide + Dexamethasone for Multiple Myeloma

(CANOVA Trial)

Not currently recruiting at 353 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must not be taking: BCL-2 inhibitors, Pomalidomide

Disqualifiers: Other malignancies, GvHD, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 28

Duration: Up to approximately 43 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drug combinations to determine which better slows multiple myeloma, a type of blood cancer. One group will take venetoclax (a targeted therapy) and dexamethasone, while the other will take pomalidomide and dexamethasone. The trial targets individuals with multiple myeloma who have a specific gene change (t(11;14)-positive) and have tried at least two other treatments without success. Participants should have experienced disease progression after their last treatment. Meeting these criteria could allow participation in the trial, potentially aiding in the discovery of better treatment options. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have been treated with venetoclax, pomalidomide, or similar drugs before, you cannot participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that patients generally tolerate the combination of venetoclax and dexamethasone well. Studies have found this combination safe for individuals with multiple myeloma, with no new safety concerns compared to other uses of venetoclax.

Similarly, the combination of pomalidomide and dexamethasone has proven safe and effective. It is often used for patients with multiple myeloma and has not shown any unexpected safety issues. One study found it well-tolerated by Chinese patients with relapsed or hard-to-treat multiple myeloma.

Both treatment combinations in this trial have been studied before and have shown general safety for people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they offer new approaches to managing the disease. Venetoclax, used in the VenDex arm, targets a specific protein called BCL-2, which helps cancer cells survive. This is different from most treatments that don't specifically target BCL-2. Meanwhile, pomalidomide in the PomDex arm is an immune-modulating drug that enhances the immune system's ability to fight cancer cells, offering a different mechanism compared to traditional chemotherapy. Together, these treatments provide fresh strategies for tackling multiple myeloma, potentially improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

This trial will compare two treatment combinations for multiple myeloma. Studies have shown that venetoclax with dexamethasone, which participants in one arm of this trial may receive, is promising for treating multiple myeloma, especially in patients with the genetic marker t(11;14). One study found that 92% of patients responded well to this treatment and experienced a longer period without disease progression. Meanwhile, research on another treatment combination in this trial, pomalidomide with dexamethasone, also shows effectiveness. Pomalidomide has been a standard treatment since 2013 and has helped patients live longer, even after trying other treatments. Both treatment combinations are supported by strong evidence, making them good options for treating this condition. ^{6 7 8 9 10}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for adults with t(11;14)-positive multiple myeloma who have tried at least two treatments, including lenalidomide and a proteasome inhibitor, but their cancer has come back or didn't respond. They should be relatively active (ECOG ≤2) and have normal organ function tests. People can't join if they've had certain other cancers recently, previous treatment with BCL-2 inhibitors like venetoclax or pomalidomide, complications from stem cell transplants, or brain involvement of MM.

Inclusion Criteria

I have completed at least 2 cycles of a proteasome inhibitor treatment.

My cancer has a specific genetic feature (t(11;14)) confirmed by a lab test.

Your liver, kidney, and blood test results need to meet certain requirements as described in the study guidelines.

Exclusion Criteria

Concurrent conditions as listed in the protocol

I haven't had a stem cell transplant in the last 3-4 months.

I have been treated with venetoclax or similar drugs before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Venetoclax and Dexamethasone or Pomalidomide and Dexamethasone in 28-day cycles

Up to approximately 43 months

Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 51 months

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Pomalidomide
• Venetoclax

Trial Overview The study compares the effectiveness of Venetoclax plus Dexamethasone (VenDex) against Pomalidomide plus Dexamethasone (PomDex) in controlling multiple myeloma without it getting worse. Participants will be randomly assigned to one of these treatment combinations to see which works better.

How Is the Trial Designed?

Group I: Arm 1 VenDex Experimental Treatment 2 Interventions

Venetoclax administered orally once daily (QD) plus dexamethasone administered orally once every week (Q1W) for each 28-day cycle.

Group II: Arm 2 PomDex Active Control 2 Interventions

Pomalidomide administered orally once daily (QD) on Days 1 - 21 for each 28-day cycle plus dexamethasone administered orally once every week (Q1W) for each 28-day cycle.

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

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Roche-Genentech

Industry Sponsor

Trials

27

Recruited

3,800+

Published Research Related to This Trial

Dexamethasone (Dex) significantly reduces the sensitivity of C6 glioma cells to methotrexate (MTX), allowing more cells to survive even at high concentrations of MTX.

This protective effect of Dex was also observed in human TE671 cells, indicating that the interaction between Dex and MTX is not limited to a specific species.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone induced partial resistance to methotrexate in C6-glioma cells. Wolff, JE., Jürgens, H.[2013]

In a study of 93 women undergoing laparoscopic gynecologic surgery, intravenous dexamethasone (both 4mg and 8mg) was more effective than ondansetron (4mg) in preventing postoperative nausea and vomiting (PONV), with the ondansetron group experiencing a 61% incidence of PONV compared to lower rates in the dexamethasone groups.

Dexamethasone not only reduced the incidence of PONV but also resulted in fewer requests for rescue antiemetics, particularly in the 4mg group, indicating it is a safe and cost-effective option for PONV prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of dexamethasone and ondansetron for prophylaxis of postoperative nausea and vomiting in laparoscopic gynecologic surgery. D'souza, N., Swami, M., Bhagwat, S.[2022]

Pomalidomide, combined with low-dose dexamethasone, has been shown to be effective in treating adult patients with relapsed and refractory multiple myeloma, significantly improving progression-free survival and overall response rates compared to high-dose dexamethasone.

The treatment demonstrated a manageable safety profile and was effective across various patient subgroups, including those who were refractory to previous therapies, indicating its potential as a valuable salvage therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. Scott, LJ.[2022]

In a meta-analysis of seven trials with 608 patients, dexamethasone was found to be as effective as ondansetron in preventing postoperative nausea and vomiting (PONV) after laparoscopic surgery, with no significant differences in safety.

Dexamethasone was more effective than ondansetron in the late postoperative stage (6-24 hours), while ondansetron was better in the early stage (0-6 hours), suggesting that both medications have specific advantages depending on the timing of administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone versus ondansetron in the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic surgery: a meta-analysis of randomized controlled trials. Wang, XX., Zhou, Q., Pan, DB., et al.[2018]

In a study of 34 lenalidomide-refractory multiple myeloma patients, the combination of pomalidomide and dexamethasone showed a 47% overall response rate, with some patients achieving very good partial responses and partial responses.

The treatment was well tolerated, although 53% of patients experienced significant hematologic toxicity, including anemia and neutropenia, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Lacy, MQ., Hayman, SR., Gertz, MA., et al.[2022]

Pomalidomide, when combined with low-dose dexamethasone, significantly improves progression-free survival and overall survival in adults with relapsed and refractory multiple myeloma, based on results from multinational phase II and III studies involving patients who had undergone at least two prior treatments.

The treatment has a manageable safety profile, with the most common serious side effects being neutropenia, infections, anemia, and thrombocytopenia, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Hoy, SM.[2018]

In a phase 3 trial involving 455 patients with refractory or relapsed multiple myeloma, pomalidomide combined with low-dose dexamethasone significantly improved progression-free survival and overall survival compared to high-dose dexamethasone.

The treatment was effective across all patient subgroups, regardless of their previous treatments, and showed no cross-resistance with prior therapies, making it a strong candidate for standard care in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma. San Miguel, JF., Weisel, KC., Song, KW., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10660104/

The real‐world use and efficacy of pomalidomide for ... Pomalidomide‐dexamethasone (Pd) has been a standard care treatment for relapsed and refractory multiple myeloma since 2013.

2. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)00266-6/fulltext

Pomalidomide, Cyclophosphamide, and Dexamethasone ... The addition of cyclophosphamide to pomalidomide and dexamethasone (PCd) demonstrated promising efficacy in relapsed/refractory multiple myeloma ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3291492/

Pomalidomide plus low-dose dexamethasone in myeloma ... Pomalidomide at doses of 2 or 4 mg/d has demonstrated excellent activity in patients with multiple myeloma (MM). We opened 2 sequential phase 2 trials using ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2152265023002288

A Meta-Analysis of the Efficacy of Pomalidomide-Based ... Pomalidomide-based combination regimens were effective in patients with RRMM previously treated with lenalidomide and tended to be associated with better ...

5. nature.com nature.com/articles/s41408-025-01356-z

an Asian Myeloma Network study (AMN003) Pomalidomide has been shown to improve survival in patients with relapsed/refractory myeloma (RRMM). However, the optimal pomalidomide-based ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35778685/

a multicenter, prospective, single-arm, phase 2 trial Conclusions: Pomalidomide in combination with low-dose dexamethasone is effective and safe in Chinese RRMM patients. Trial registration: The ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02119468

Ixazomib Plus Pomalidomide and Dexamethasone in ... Giving ixazomib with pomalidomide and dexamethasone may be an effective treatment for relapsed or relapsed/refractory multiple myeloma.

8. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7876/527017/Efficacy-and-Safety-of-Daratumumab-Plus

Efficacy and Safety of Daratumumab Plus Pomalidomide and ... The overall response rate (ORR) was 94% with 67% achieving a complete response or better. After a median follow-up of 12.5 months (range 1-17), ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2152265024002854

Pomalidomide/Daratumumab/Dexamethasone in ... At a median follow-up of 13.1 months, overall response rate (ORR) was 60.2%, median progression-free survival (PFS) was 8.8 months, and median overall survival ...

10. onclive.com onclive.com/view/cevostamab-plus-pomalidomide-dexamethasone-is-safe-active-in-r-r-myeloma

Cevostamab Plus Pomalidomide/Dexamethasone Is Safe ... For patients in the 70-mg cohort, the overall response rate (ORR) was 86.2% (95% CI, 71.9%-100%). The rates of stringent complete response (sCR) ...