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

46 Participants Needed

Trial Summary

What is the purpose of this trial?

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 allow researchers to collect your stem cells in case it is possible to transplant the stem cells as treatment if your WM gets worse. Researchers will also look at the safety and tolerability of this drug combination followed by treatment with other drug combinations.

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.

What data supports the effectiveness of the drug combination Bortezomib and Rituximab for treating Waldenström's Macroglobulinemia?

Research shows that the combination of bortezomib, dexamethasone, and rituximab (BDR) has been effective in treating Waldenström's Macroglobulinemia, with an overall response rate of 84% in treatment-naïve patients. Additionally, bortezomib has shown significant activity in this condition, supporting its use in combination with rituximab. ^{1 2 3 4 5}

Is the combination of Bortezomib and Rituximab safe for humans?

The combination of Bortezomib and Rituximab has been studied for safety in patients with Waldenström's Macroglobulinemia. Common side effects include peripheral neuropathy (nerve damage causing tingling or numbness) and blood-related issues like neutropenia (low white blood cell count), anemia (low red blood cell count), and thrombocytopenia (low platelet count), but these were generally manageable and reversible. ^{6 7 8 9 10}

How is the drug combination of Bortezomib and Rituximab unique for treating Waldenström's Macroglobulinemia?

The combination of Bortezomib and Rituximab is unique because Bortezomib is a proteasome inhibitor that has shown significant activity in various blood cancers, and when combined with Rituximab, it offers a rapidly acting and well-tolerated treatment option for Waldenström's Macroglobulinemia, inducing durable responses without causing significant bone marrow suppression. ^{1 2 4 8 11}

Research Team

Sheeba Thomas, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

References

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

Primary therapy of Waldenström macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. [2023]

2. United States 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. [2023]

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

Assessment of fixed-duration therapies for treatment-naïve Waldenström macroglobulinemia. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Bendamustine and rituximab (BR) versus dexamethasone, rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia. [2018]

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

Bendamustine and rituximab combination is safe and effective as salvage regimen in Waldenström macroglobulinemia. [2022]

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

Bortezomib is active in patients with untreated or relapsed Waldenstrom's macroglobulinemia: a phase II study of the National Cancer Institute of Canada Clinical Trials Group. [2015]

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

Phase II trial of weekly bortezomib in combination with rituximab in relapsed or relapsed and refractory Waldenstrom macroglobulinemia. [2022]

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

Primary therapy of Waldenstrom macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR): long-term results of a phase 2 study of the European Myeloma Network (EMN). [2022]

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

Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenström Macroglobulinemia. [2022]

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

Rituximab-based combination therapy in patients with Waldenström macroglobulinemia: a systematic review and meta-analysis. [2022]

11. Italy pubmed.ncbi.nlm.nih.gov

Treatment of relapsed or refractory Waldenström's macroglobulinemia with bortezomib. [2015]