Vemurafenib + Obinutuzumab for Hairy Cell Leukemia

Not currently recruiting at 10 trial locations

Overseen By Jae Park, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Purine analogs, Rituximab

Disqualifiers: Liver disease, Uncontrolled infections, 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: 2

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on a new treatment combination for individuals with untreated hairy cell leukemia, a rare blood cancer. Researchers are testing the effectiveness of combining vemurafenib, a pill targeting specific cancer cell mutations, with obinutuzumab, an antibody that aids the immune system in fighting cancer. The trial seeks individuals diagnosed with hairy cell leukemia who have not yet received treatment. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in leukemia treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are taking medications that could interact with vemurafenib or obinutuzumab, you may need to discuss this with the trial team.

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

Research shows that the combination of vemurafenib and obinutuzumab is generally well-tolerated by patients with hairy cell leukemia (HCL). In a previous study, this treatment led to complete remission in over 90% of patients who had not been treated before, indicating its effectiveness and manageability for most people.

Vemurafenib, a BRAF inhibitor, has been used safely in other conditions and tends to cause fewer side effects than traditional chemotherapy. Obinutuzumab, an antibody treatment, has also proven effective in similar blood cancers and usually presents fewer side effects than some other treatments.

While side effects may occur, as with any treatment, research and past patient experiences support the safety of this combination therapy. Patients should always discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Vemurafenib and Obinutuzumab for treating Hairy Cell Leukemia (HCL) because they offer a unique approach compared to current standard treatments, such as purine analogs like cladribine and pentostatin. Vemurafenib targets a specific mutation in the BRAF gene, which is common in HCL, potentially offering a more precise method of attacking cancer cells. Meanwhile, Obinutuzumab is a monoclonal antibody that targets CD20, a protein found on the surface of B-cells, helping the immune system to better detect and destroy cancerous cells. Together, these treatments provide a dual mechanism of action, aiming to improve efficacy and potentially offer options for patients who have not yet received any treatment.

What evidence suggests that the combination of vemurafenib and obinutuzumab could be effective for untreated hairy cell leukemia?

This trial will evaluate the combination of vemurafenib and obinutuzumab for treating untreated hairy cell leukemia (HCL). Research has shown that using vemurafenib and obinutuzumab together yields promising results for HCL. In earlier studies, more than 90% of patients with untreated HCL achieved complete remission with this treatment. Vemurafenib targets a specific protein in cancer cells and has proven effective for patients whose HCL returned or did not respond to other treatments. When combined with obinutuzumab, a type of antibody therapy, it may destroy more cancer cells than traditional chemotherapy. These findings suggest that this combination could be highly effective for individuals who have not yet received treatment for their HCL. ^{5 6 7 8 9}

Who Is on the Research Team?

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with previously untreated classical Hairy Cell Leukemia who meet specific blood count criteria and are in good physical condition. They must have normal organ function, agree to use contraception, and not be pregnant. Excluded are those with hepatitis B or C, HIV, other cancers needing treatment that could interact with the trial drugs, uncontrolled infections, or a history of liver disease.

Inclusion Criteria

My organs are functioning well according to recent tests.

Patients who meet the standard treatment initiation criteria, as defined by ANC </=1.0, Hgb </=10.0 or PLT </=100K

Total bilirubin </= 1.5 times the upper limit of normal (ULN)

Exclusion Criteria

I have been diagnosed with HIV or HTLV-1.

You have severe allergies to any of the study drugs.

Patients with uncorrectable electrolyte abnormalities with potassium (K) >ULN (upper limit of normal).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vemurafenib and obinutuzumab over 4 cycles of 4 weeks each

16 weeks

Cycle 2: 3 visits (in-person), Cycles 3-4: 1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including bone marrow aspirate and biopsy

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Obinutuzumab
• Vemurafenib

Trial Overview The trial is testing an oral drug called Vemurafenib combined with Obinutuzumab infusions against Hairy Cell Leukemia. Initially, 9 patients will receive this combination to see if it's effective; if successful, another 19 will join. The treatment spans over four cycles (16 weeks), followed by bone marrow tests for response evaluation.

How Is the Trial Designed?

Group I: Untreated Hairy Cell Leukemia Experimental Treatment 2 Interventions

Participants with HCL with no prior treatment for the disease

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

Approved in United States as Gazyva for:

• Chronic Lymphocytic Leukemia (CLL)
• Follicular Lymphoma

Approved in European Union as Gazyva for:

• Chronic Lymphocytic Leukemia (CLL)
• Follicular Lymphoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Yale University

Collaborator

Trials

1,963

Recruited

3,046,000+

Published Research Related to This Trial

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]

Obinutuzumab is an effective treatment for B-cell malignancies, specifically approved in the US for chronic lymphocytic leukaemia (CLL) in combination with chlorambucil, showcasing its efficacy in targeting cancer cells.

Utilizing GlycoMAb® technology, obinutuzumab enhances immune-mediated cell death through increased antibody-dependent cellular cytotoxicity, making it a promising option in ongoing phase III trials for various B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: first global approval. Cameron, F., McCormack, PL.[2021]

Vemurafenib, an oral BRAF inhibitor, demonstrated a high overall response rate of 96% in an Italian study and 100% in a U.S. study for patients with relapsed or refractory hairy-cell leukemia, with treatment durations averaging 16 to 18 weeks.

The treatment was generally safe, with most adverse events being mild (grade 1 or 2), although some patients developed secondary cutaneous tumors, indicating the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Mutant BRAF in Relapsed or Refractory Hairy-Cell Leukemia. Tiacci, E., Park, JH., De Carolis, L., et al.[2022]

Obinutuzumab combined with chlorambucil shows better treatment outcomes for patients with untreated chronic lymphocytic leukemia compared to rituximab plus chlorambucil, while maintaining a similar safety profile.

Infusion-related reactions (IRRs) are more common with obinutuzumab, particularly during the first infusion, but these reactions are generally manageable with proper monitoring and management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing Infusion-Related Reactions for Patients With Chronic Lymphocytic Leukemia Receiving Obinutuzumab. Dawson, K., Moran, M., Guindon, K., et al.[2017]

In a multinational phase III study, obinutuzumab combined with chlorambucil significantly improved progression-free survival and event-free survival in adults with previously untreated chronic lymphocytic leukaemia (CLL) compared to chlorambucil alone and rituximab plus chlorambucil.

Obinutuzumab plus chlorambucil had a manageable safety profile, with neutropenia and infusion-related reactions being the most common serious side effects, primarily occurring during the first infusion and generally manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: a review of its use in patients with chronic lymphocytic leukaemia. Hoy, SM.[2018]

In a study of 123 patients with hairy cell leukemia (HCL) diagnosed between 1996 and 2016, cladribine as a first-line treatment resulted in a high hematological complete response rate of 92%, demonstrating its efficacy in managing this rare cancer.

The median overall survival for HCL patients was over 15 years, with 5-year and 10-year survival rates of 84% and 70.5%, indicating a favorable long-term prognosis, especially compared to other treatments like IFN-α which had a higher relapse rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A population-based study of hairy cell leukemia over a period of 20 years. Wiber, M., Maitre, E., Poncet, JM., et al.[2021]

Hairy cell leukemia (HCL) is effectively treated with purine analogs, but about half of patients relapse and may become resistant to these treatments, necessitating alternative therapies.

Targeting the BRAF-V600E mutation with specific inhibitors like vemurafenib or dabrafenib offers a promising chemotherapy-free strategy, especially for patients at risk of severe infections or those with relapsed HCL, and can be combined with rituximab for enhanced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I treat refractory/relapsed hairy cell leukemia with BRAF inhibitors. Falini, B., De Carolis, L., Tiacci, E.[2022]

Obinutuzumab, combined with bendamustine, significantly prolonged progression-free survival (PFS) in patients with indolent non-Hodgkin's lymphoma, particularly benefiting those with follicular lymphoma, as shown in the phase III GADOLIN study.

The treatment was generally well-tolerated, with mild to moderate infusion-related reactions being the most common side effects, while neutropenia was the most frequent severe adverse event, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma. Dhillon, S.[2018]

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]

Citations

1. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2300074

Vemurafenib and Obinutuzumab as Frontline Therapy for ... Combined time-limited vemurafenib and obinutuzumab achieved CR in more than 90% of patients with previously untreated HCL.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9935554/

Long-term outcomes in patients with relapsed or refractory ... Vemurafenib, an oral BRAF inhibitor, has demonstrated high response rates in relapsed/refractory (R/R) hairy cell leukemia (HCL). However, little is known about ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06561360

NCT06561360 | A Study of Vemurafenib and ... Researchers think vemurafenib and obinutuzumab (non-chemotherapy drugs) may cause fewer side effects compared with the usual approach of chemotherapy drugs.

4. ashpublications.org ashpublications.org/ashclinicalnews/news/8060/Forging-a-New-Standard-of-Care-for-Hairy-Cell

Forging a New Standard of Care for Hairy Cell Leukemia Initially, vemurafenib was shown to be effective as a finite course of therapy among patients with relapsed or refractory HCL in phase II trials ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-07627

Vemurafenib and Obinutuzumab versus Standard ... Giving vemurafenib and obinutuzumab may kill more cancer cells in patients with previously untreated hairy cell leukemia compared to standard cladribine and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38320179/

Vemurafenib and Obinutuzumab as Frontline ... - PubMed - NIH CONCLUSIONS: Combined time-limited vemurafenib and obinutuzumab achieved CR in more than 90% of patients with previously untreated HCL. In this small study, ...

7. evidence.nejm.org evidence.nejm.org/doi/pdf/10.1056/EVIDoa2300074

Vemurafenib and Obinutuzumab as Frontline Therapy for ... Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib mono- therapy. Blood 2022;140:2663 ...

8. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4398/502472/Efficacy-and-Safety-of-Obinutuzumab-in-Relapsed-or

Efficacy and Safety of Obinutuzumab in Relapsed or ... Obinutuzumab (OBI) is a more effective anti-CD20 agent than rituximab (RTX) in other indolent B-cell neoplasms such as chronic lymphocytic leukemia and ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06561360

A Study of Vemurafenib and Obinutuzumab Compared to ... Researchers think vemurafenib and obinutuzumab (non-chemotherapy drugs) may cause fewer side effects compared with the usual approach of chemotherapy drugs.