Venetoclax + Dexamethasone vs Pomalidomide + Dexamethasone for Multiple Myeloma

(CANOVA Trial)

Recruiting at 302 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

265 Participants Needed

Trial Summary

What is the purpose of this trial?

A study designed tocompare progression-free survival (PFS) in participants with t(11;14)-positive MM treated with venetoclax in combination with dexamethasone versus pomalidomide in combination with dexamethasone.

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.

What data supports the effectiveness of the drug combination Pomalidomide and Dexamethasone for treating multiple myeloma?

Research shows that Pomalidomide combined with low-dose Dexamethasone is effective in treating relapsed and refractory multiple myeloma, leading to longer survival and better response rates compared to high-dose Dexamethasone alone. This combination is especially beneficial for patients who have already tried other treatments like lenalidomide and bortezomib. ^{1 2 3 4 5}

Is dexamethasone generally safe for use in humans?

Dexamethasone is commonly used to prevent nausea and vomiting after surgery and is generally considered safe for these purposes. However, it may cause partial resistance to certain chemotherapy drugs in cancer treatment. ^{6 7 8 9 10}

What makes the drug combination of Venetoclax, Pomalidomide, and Dexamethasone unique for treating Multiple Myeloma?

This drug combination is unique because it combines Venetoclax, which targets a specific protein in cancer cells to induce cell death, with Pomalidomide, which modulates the immune system, and Dexamethasone, a steroid that reduces inflammation. This multi-faceted approach may offer a novel way to tackle Multiple Myeloma by attacking the cancer from different angles. ^{6 7 9 10 11}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Concurrent conditions as listed in the protocol

I have been treated with venetoclax or similar drugs before.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. Italy pubmed.ncbi.nlm.nih.gov

Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

5. Italy 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. [2022]

6. France pubmed.ncbi.nlm.nih.gov

The effects of dexamethasone added to ilioinguinal/iliohypogastric nerve (IIN/IHN) block on rebound pain in inguinal hernia surgery: a randomized controlled trial. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Prophylactic antiemetic therapy with granisetron-dexamethasone combination in women undergoing breast surgery. [2019]

8. Greece pubmed.ncbi.nlm.nih.gov

Dexamethasone induced partial resistance to methotrexate in C6-glioma cells. [2013]

9. England 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. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Comparative study of dexamethasone and ondansetron for prophylaxis of postoperative nausea and vomiting in laparoscopic gynecologic surgery. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Comparison of Ondansetron and Dexamethasone for Prophylaxis of Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Surgeries: A Meta-Analysis of Randomized Controlled Trials. [2022]