Vemurafenib + Rituximab for Hairy Cell Leukemia

Recruiting at 1 trial location

Overseen By Alan Saven, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Scripps Health

Must not be taking: Chemotherapy, Rituximab, BRAF inhibitors

Disqualifiers: Pregnancy, Recent surgery, Active HIV, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 8

Duration: 16 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The current standard-of-care for Hairy Cell Leukemia involves chemotherapy, with agents such as cladribine or pentostatin. Chemotherapy is associated with infection, low blood counts and predisposition to future cancers. This study tests a new yet previously validated drug combination for the treatment of hairy cell leukemia. The treatment involves 8 weeks of treatment with an oral drug called vemurafenib and 8 doses of an intravenous medication called rituximab. The goal of this study is to see whether this treatment is better tolerated and more effective than the currently used treatment in this disease. In addition, this study uses a lower dose of vemurafenib than previous studies have used, with the goal of minimizing side effects from this medication.

Will I have to stop taking my current medications?

The trial requires that you have not had chemotherapy, rituximab, or other investigational agents within six weeks before starting, and no BRAF inhibitor therapy within six months. If you're on these medications, you would need to stop them before joining the trial.

What data supports the effectiveness of the drug combination Vemurafenib and Rituximab for treating Hairy Cell Leukemia?

Research shows that Rituximab has been effective in treating relapsed Hairy Cell Leukemia, leading to complete remission in some cases. Additionally, a meta-analysis found that Vemurafenib treatment had a high response rate of up to 99% in Hairy Cell Leukemia patients, suggesting potential effectiveness when combined with Rituximab. ^{1 2 3 4 5}

Is the combination of Vemurafenib and Rituximab safe for treating hairy cell leukemia?

The combination of Vemurafenib and Rituximab is emerging as a safe treatment option for hairy cell leukemia, with studies indicating it is a short, chemotherapy-free regimen that can induce deep remissions in patients who have relapsed or are refractory to other treatments. Rituximab alone has shown minimal toxicity in patients with hairy cell leukemia, suggesting a favorable safety profile. ^{1 4 6 7 8}

How is the drug combination of Vemurafenib and Rituximab unique for treating hairy cell leukemia?

The combination of Vemurafenib and Rituximab is unique for treating hairy cell leukemia because it targets the BRAF-V600E mutation, which is the genetic cause of the disease, and offers a chemotherapy-free option that can induce deep remissions even in patients who have relapsed multiple times after other treatments. ^{4 6 7 9 10}

Research Team

Alan Saven, MD

Principal Investigator

Scripps Clinic

Eligibility Criteria

This trial is for adults with Hairy Cell Leukemia that's BRAF V600E positive. They should have normal organ function, not be pregnant or breastfeeding, and agree to use contraception. It's open to those who haven't had treatment before, didn't respond to initial therapy, or relapsed after any treatment.

Inclusion Criteria

I agree to use barrier contraception if my partner can have children.

My liver and kidney functions are within acceptable ranges.

My HCL cancer is confirmed to be BRAF V600E positive.

Exclusion Criteria

I haven't had chemotherapy, rituximab, or BRAF inhibitors recently.

I haven't had cancer, except for certain types treated with the intent to cure, in the last 2 years.

Known hypersensitivity to any of the study drugs

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vemurafenib orally twice daily for 8 weeks and rituximab intravenously every 2 weeks for 16 weeks

16 weeks

8 visits (in-person) for rituximab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including bone marrow assessment at 6 months

Up to 2 years

Treatment Details

Interventions

• Rituximab
• Vemurafenib

Trial Overview The study tests a combination of low dose vemurafenib (oral) and rituximab (IV) over 8 weeks. This approach aims to see if it's more effective and better tolerated than standard chemotherapy treatments for this type of leukemia.

Participant Groups

Group I: Low dose Vemurafenib and Rituximab Experimental Treatment 1 Intervention

Eligible patients will receive vemurafenib at a dose of 240 mg orally twice daily (b.i.d.) continuously for 8 weeks. Rituximab 375 mg/m2 will be administered every 2 weeks for a total of 16 weeks. The entire duration of treatment will be 16 weeks.

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

Approved in United States as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in European Union as MabThera for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in Canada as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Who Is Running the Clinical Trial?

Scripps Health

Lead Sponsor

Trials

59

Recruited

43,400+

Findings from Research

Bendamustine-rituximab (BR) treatment showed a 100% overall response rate in patients with multiply relapsed/refractory hairy cell leukemia, with significant complete remission rates of 50% and 67% for the 70 mg/m² and 90 mg/m² dose groups, respectively.

The treatment was well-tolerated, with no significant dose-related differences in efficacy or toxicity, and the 90 mg/m² dose was selected for future studies due to its effectiveness and manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine and rituximab in relapsed and refractory hairy cell leukemia. Burotto, M., Stetler-Stevenson, M., Arons, E., et al.[2022]

A 46-year-old man with relapsing hairy cell leukemia achieved complete remission for over 9 months after treatment with rituximab, a monoclonal anti-CD20 antibody, administered at 375 mg/week for four weeks.

Rituximab was more effective than previous treatments (alpha-interferon and chlorodeoxyadenosine) and did not cause the initial worsening of pancytopenia that is often seen with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric monoclonal anti-CD20 antibody (rituximab)--an effective treatment for a patient with relapsing hairy cell leukaemia. Hagberg, H.[2019]

A patient with hairy cell leukemia, who had relapsed after multiple treatments, achieved a complete response after being treated with rituximab.

The treatment resulted in a fourfold reduction of leukemic cells and restored normal blood counts, indicating rituximab's efficacy in this case.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: a useful drug for a repeatedly relapsed hairy cell leukemia patient. Pollio, F., Pocali, B., Palmieri, S., et al.[2015]

Moxetumomab pasudotox is an FDA-approved treatment for relapsed or refractory hairy cell leukemia, based on a pivotal phase III study demonstrating its efficacy in this rare cancer.

The treatment targets the CD22 protein on B-cells, and while it can lead to durable remission, practitioners should be aware of common adverse effects and management strategies as its use becomes more widespread.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moxetumomab pasudotox: A first-in-class treatment for hairy cell leukemia. Fancher, KM., Lally-Montgomery, ZC.[2019]

A meta-analysis of 21 studies involving various treatments for hairy cell leukemia found that cladribine combined with rituximab and vemurafenib achieved a remarkable response rate of 99%.

Cladribine with rituximab was identified as the most effective therapy, especially for treatment-naïve patients and those in their first relapse, with a complete response rate of 97%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to the Therapy in Hairy Cell Leukemia: Systematic Review and Meta-Analysis. Andrasiak, I., Rybka, J., Wrobel, T.[2019]

Hairy cell leukemia (HCL) initially responds well to chemotherapy, but up to 50% of patients relapse and become less sensitive to these treatments, highlighting the need for alternative therapies.

Recent advancements, particularly the combination of vemurafenib (a BRAF inhibitor) and rituximab, show promise as a safe, chemotherapy-free treatment option that can induce deep complete remissions in patients with relapsed or refractory HCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New treatment options in hairy cell leukemia with focus on BRAF inhibitors. Falini, B., Tiacci, E.[2019]

Moxetumomab pasudotox (Lumoxiti®) is an effective treatment for adults with relapsed or refractory hairy cell leukaemia, achieving a durable complete response in about one-third of patients in a pivotal phase III trial.

The treatment has a manageable safety profile, with common side effects like nausea and headache, and serious adverse events such as haemolytic uraemic syndrome are generally reversible with proper monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moxetumomab Pasudotox in Hairy Cell Leukaemia: A Profile of Its Use. Kang, C.[2021]

Rituximab demonstrated an overall response rate of 80% in 15 patients with relapsed or refractory hairy cell leukemia, with 53% achieving complete response, indicating its efficacy as a treatment option.

The treatment was well-tolerated with minimal toxicity and no observed infectious episodes, suggesting that rituximab is a safe option for patients with this type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in relapsed or refractory hairy cell leukemia. Thomas, DA., O'Brien, S., Bueso-Ramos, C., et al.[2021]

In a case study of four relapsed hairy cell leukemia patients, treatment with vemurafenib combined with rituximab led to significant responses, including two patients achieving minimal residual disease negative complete responses after prior therapies failed.

The use of vemurafenib and rituximab improved outcomes for heavily pretreated patients, suggesting that these targeted therapies can enhance the prognosis for those with relapsed hairy cell leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vemurafenib and Rituximab in Patients with Hairy Cell Leukemia Previously Treated with Moxetumomab Pasudotox. Robak, T., Janus, A., Jamroziak, K., et al.[2021]

The discovery of the BRAF-V600E mutation in nearly all patients with hairy cell leukemia (HCL) provides a genetic basis for the disease and allows for a genetics-based differential diagnosis, distinguishing HCL from similar B-cell neoplasms.

Treatment with the BRAF inhibitor vemurafenib has shown an almost 100% response rate in patients with relapsed HCL, achieving complete remission in 35% to 42% of cases, and importantly, this treatment does not cause myelotoxicity, making it a promising therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomics of Hairy Cell Leukemia. Tiacci, E., Pettirossi, V., Schiavoni, G., et al.[2018]

References

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

Bendamustine and rituximab in relapsed and refractory hairy cell leukemia. [2022]

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

Chimeric monoclonal anti-CD20 antibody (rituximab)--an effective treatment for a patient with relapsing hairy cell leukaemia. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Rituximab: a useful drug for a repeatedly relapsed hairy cell leukemia patient. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Moxetumomab pasudotox: A first-in-class treatment for hairy cell leukemia. [2019]

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

Response to the Therapy in Hairy Cell Leukemia: Systematic Review and Meta-Analysis. [2019]

6. England pubmed.ncbi.nlm.nih.gov

New treatment options in hairy cell leukemia with focus on BRAF inhibitors. [2019]

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

Moxetumomab Pasudotox in Hairy Cell Leukaemia: A Profile of Its Use. [2021]

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

Rituximab in relapsed or refractory hairy cell leukemia. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Vemurafenib and Rituximab in Patients with Hairy Cell Leukemia Previously Treated with Moxetumomab Pasudotox. [2021]

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

Genomics of Hairy Cell Leukemia. [2018]