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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination for treating hairy cell leukemia, a rare blood cancer. The treatment involves a low dose of the oral drug vemurafenib and the intravenous medication rituximab. The researchers aim to determine if this combination is more effective and gentler on the body than traditional chemotherapy. Individuals diagnosed with hairy cell leukemia that tests positive for the BRAF V600E mutation and who have experienced issues with previous treatments might be suitable candidates for this study. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that combining vemurafenib and rituximab is generally well-tolerated for treating hairy cell leukemia. Studies have found that many patients went into complete remission without serious side effects. Most did not experience major infections, with the main issue being a mild skin rash. This study uses a lower dose of vemurafenib to further reduce side effects. Overall, this treatment appears safer than traditional chemotherapy, which often causes infections and other serious problems. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Vemurafenib and Rituximab for treating Hairy Cell Leukemia because this combination targets the cancer in a new way. Unlike standard treatments like chemotherapy, Vemurafenib specifically inhibits the BRAF mutation, which is often present in this type of leukemia. Rituximab, on the other hand, is an antibody that targets the CD20 protein on cancer cells, enhancing the immune system's ability to destroy them. This targeted approach may offer more effective and potentially less toxic treatment options compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for Hairy Cell Leukemia?

This trial will evaluate the combination of vemurafenib and rituximab for treating hairy cell leukemia. Research has shown that using these drugs together may be effective. One study reported that 85% of participants remained free of the disease for almost three years. Another study found a 78% chance of patients not seeing their disease worsen over 37 months. Additionally, a study using a lower dose of vemurafenib reported that all participants stayed free of disease relapse for 303 days without severe side effects. These results suggest that this treatment might work better and be easier to tolerate than traditional chemotherapy. ^{2 4 6 7 8}

Who Is on the Research Team?

Alan Saven, MD

Principal Investigator

Scripps Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2031298

Vemurafenib plus Rituximab in Refractory or Relapsed ... Progression-free survival among all 30 patients was 78% at a median follow-up of 37 months; relapse-free survival among the 26 patients with a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05388123

Low Dose Vemurafenib and Rituximab in Hairy Cell ... 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, ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4413/502821/A-Single-Arm-Phase-II-Pilot-Study-of-Low-Dose

A Single Arm Phase II Pilot Study of Low Dose Vemurafenib ... At a median follow-up time of 303 days, the relapse-free survival rate was 100%. There were no adverse grade 3 or 4 adverse events and no ...

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2021/hairy-cell-leukemia-vemurafenib-rituximab

Vemurafenib and Rituximab for Hairy Cell Leukemia - NCI In a small study, vemurafenib (Zelboraf) and rituximab (Rituxan) helped 85% of participants stay in remission for nearly 3 years.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212624000614

Single agent vemurafenib or rituximab- ... These agents result in complete response (CR) rates of 85–90% [5], [6], [7]. It is also effective in re-induction. However, relapse remains an important problem ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33979489/

Vemurafenib plus Rituximab in Refractory or Relapsed ... A complete response was observed in 26 patients (87%) in the intention-to-treat population. All the patients who had HCL that had been ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123096295

Real-Life Efficacy and Safety of Vemurafenib Plus ... A short chemotherapy-free regimen of the BRAF inhibitor vemurafenib (V) + rituximab (R; Mabthera) led to 87% complete remissions (CR), 60% MRD-negativity and ...

8. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(20)30914-9/fulltext

IBCL-386: Rituximab-Vemurafenib Combination for the ... Rituximab and Vemurafenib were all tolerated well with no documented infectious complications. The only dose-limiting complication reported was grade 2 maculo- ...