Bortezomib + Rituximab for Waldenström's Macroglobulinemia

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Heart disease, Neuropathy, Active cancer, others

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

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

Compensation: Varies

Number of Visits: 7

Duration: 10-15 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining bortezomib (a chemotherapy drug) and rituximab (an antibody therapy) can help manage Waldenström's Macroglobulinemia (WM), a type of blood cancer. Researchers aim to determine if this drug duo can control the disease and safely collect stem cells for future treatment if needed. The trial is open to individuals with symptomatic WM who have had little to no previous treatment. Participants should have symptoms affecting daily life, such as peripheral neuropathy (nerve damage) or anemia (low red blood cell count). As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that the combination of bortezomib and rituximab is generally well-tolerated by patients with Waldenström's macroglobulinemia (WM). In studies, patients receiving this combination experienced positive results with manageable side effects.

Common side effects include tiredness, low blood cell counts, and nausea. However, these are usually mild to moderate and can be managed with proper care.

One study found that this combination was not only effective but also well-tolerated by most patients with WM. While some side effects may occur, the treatment is generally safe.

Overall, evidence indicates that using bortezomib and rituximab together can be a safe treatment option for those with WM, with side effects that are usually manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Bortezomib and Rituximab for treating Waldenström's Macroglobulinemia because it targets cancer cells in a novel way. Bortezomib is a proteasome inhibitor, which means it disrupts the protein breakdown process inside cancer cells, leading to their death. Rituximab is a monoclonal antibody that specifically targets and destroys B-cells, which are often cancerous in this condition. This dual approach not only directly attacks the cancer cells but also enhances the immune system's ability to fight the disease, potentially offering a more comprehensive and effective treatment compared to traditional chemotherapy.

What evidence suggests that this treatment might be an effective treatment for Waldenström's Macroglobulinemia?

This trial will evaluate the combination of bortezomib and rituximab for treating Waldenström's macroglobulinemia (WM). Studies have shown that this combination effectively controls the disease, offering a promising treatment option. Bortezomib and rituximab are generally well-tolerated, meaning patients usually handle them well without serious side effects. Previous patients using this combination experienced positive results in managing their condition, making the treatment a strong option for controlling WM symptoms and slowing its progression. ^{2 3 6 7 8}

Who Is on the Research Team?

Sheeba Thomas, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with Waldenstrom's Macroglobulinemia who haven't had prior treatment or only had steroids/alpha-interferon. They must have no serious heart issues, acceptable liver and kidney function, not be pregnant or breastfeeding, and willing to use birth control. People with certain health conditions like severe neuropathy, active hepatitis B, recent heart attack, other active cancers (except some skin cancers), or very low blood counts are excluded.

Inclusion Criteria

Patients must voluntarily sign an informed consent form indicating that they are aware of the investigational nature of the study, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future care.

I agree to use contraception throughout the study.

My liver and kidney functions are within the required levels, or my kidney issues are due to my lymphoma.

Exclusion Criteria

I am not pregnant or breastfeeding, confirmed by a negative pregnancy test.

My platelet count is low, but it's because of my lymphoma or enlarged spleen.

I have moderate to severe nerve damage in my hands or feet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive two 35-day cycles of bortezomib and rituximab, with additional cycles based on response

10-15 weeks

Weekly visits for drug administration

Stem Cell Collection

Stem cells are collected if participants respond to initial treatment cycles

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Every 6 months for the first 36 months, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Rituximab

Trial Overview The study tests if a combination of drugs called Bortezomib and Rituximab can manage Waldenstrom's Macroglobulinemia effectively. It also evaluates the safety of this combo followed by other treatments and checks if it allows stem cell collection for potential future transplants.

How Is the Trial Designed?

Group I: Bortezomib + Rituximab Experimental Treatment 3 Interventions

Bortezomib 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily).

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

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Millennium Pharmaceuticals, Inc.

Industry Sponsor

Trials

406

Recruited

46,900+

Dr. Christophe Bianchi

Millennium Pharmaceuticals, Inc.

Chief Medical Officer since 2006

MD from University of Geneva

Dr. Deborah Dunsire

Millennium Pharmaceuticals, Inc.

Chief Executive Officer since 2005

MD from University of Witwatersrand

Published Research Related to This Trial

In a study of 204 treatment-naïve patients with Waldenström's macroglobulinemia, the combination of bortezomib, dexamethasone, and rituximab (B-DRC) showed an 80.6% progression-free survival rate at 24 months, compared to 72.8% for the standard DRC treatment, indicating B-DRC may offer better long-term outcomes.

B-DRC resulted in higher major response rates (57.0% vs. 32.5%) and a quicker time to first response (3.0 months vs. 5.5 months) compared to DRC, while both treatments had similar safety profiles, suggesting B-DRC is both effective and well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib-Dexamethasone, Rituximab, and Cyclophosphamide as First-Line Treatment for Waldenström's Macroglobulinemia: A Prospectively Randomized Trial of the European Consortium for Waldenström's Macroglobulinemia. Buske, C., Dimopoulos, MA., Grunenberg, A., et al.[2023]

The combination therapy of bortezomib, dexamethasone, and rituximab (BDR) resulted in a high overall response rate of 96% and significant reductions in disease markers in 23 patients with untreated Waldenström macroglobulinemia, with responses observed as early as 1.4 months after starting treatment.

While BDR therapy was effective, it was associated with peripheral neuropathy as the most common side effect, necessitating adjustments in treatment schedules and the use of prophylactic antiviral therapy due to herpes zoster infections in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary therapy of Waldenström macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. Treon, SP., Ioakimidis, L., Soumerai, JD., et al.[2023]

In a study of 160 patients with Waldenstrom macroglobulinemia, the bendamustine-rituximab (BR) regimen showed a trend towards longer progression-free survival (PFS) compared to dexamethasone, rituximab plus cyclophosphamide (DRC), with 2-year PFS rates of 88% for BR versus 61% for DRC, although the difference was not statistically significant (p=0.07).

Both treatment regimens had comparable overall response rates and grade ≥3 adverse events, indicating similar safety profiles, and the effectiveness of both regimens was not influenced by the presence of the MYD88L265P mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine and rituximab (BR) versus dexamethasone, rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia. Paludo, J., Abeykoon, JP., Shreders, A., et al.[2018]

Rituximab-based combination therapy for Waldenström macroglobulinemia (WM) showed a high overall response rate of 84% across 22 studies involving 806 patients, indicating its efficacy in treating this condition.

The therapy was generally well-tolerated, with common grade ≥3 hematological adverse events like neutropenia occurring in 33% of patients, suggesting that while there are risks, the benefits of treatment outweigh the potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab-based combination therapy in patients with Waldenström macroglobulinemia: a systematic review and meta-analysis. Zheng, YH., Xu, L., Cao, C., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36763945/

Bortezomib-Dexamethasone, Rituximab, and ... Conclusion: This large randomized study illustrates that B-DRC is highly effective and well tolerated in WM. The data demonstrate that fixed ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00492050?intr=%22Bortezomib%22&viewType=Table&rank=2

Bortezomib and Rituximab for Patients With Waldenstrom's ... The main goal of this clinical research study is to learn if Velcade ® (bortezomib) given with rituximab can help to control WM. This drug combination will ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/859/530754/Bortezomib-in-Combination-with-Ibrutinib-Rituximab

Bortezomib in Combination with Ibrutinib/Rituximab Is a Highly ... Bortezomib in combination with Ibrutinib/Rituximab is a highly effective and well tolerated first-line treatment for Waldenström's macroglobulinemia.

4. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.22.01805

Bortezomib-Dexamethasone, Rituximab, and ... This study evaluated the efficacy and safety of dexamethasone, rituximab, and cyclophosphamide (DRC) as first-line treatment in WM.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124036061

Bortezomib in Combination with Ibrutinib/Rituximab Is a ... Bortezomib in Combination with Ibrutinib/Rituximab Is a Highly Effective and Well Tolerated First - Line Treatment for Waldenström's Macroglobulinemia: Results ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2834499/

Phase II Trial of Weekly Bortezomib in Combination With ... This study aimed to determine activity and safety of weekly bortezomib and rituximab in patients with relapsed/refractory Waldenström macroglobulinemia (WM).

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2037/499119/Multicenter-Prospective-Phase-II-Study-of

Multicenter Prospective Phase II Study of Rituximab ... This study was conducted to estimate the efficacy and safety of the combination of rituximab, bortezomib, lenalidomide and dexamethasone in patients with WM in ...

8. nature.com nature.com/articles/s41408-023-00916-5

Efficacy and safety of front-line treatment regimens for ... Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an ...