Low Dose Vemurafenib and Rituximab in Hairy Cell Leukemia

NCT05388123 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: IRB-21-7787
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hairy Cell Leukemia

Outcome Measures

Primary Outcomes (1)

• Complete Response

  Resolution of cytopenias and splenomegaly

  Up to 2 years from enrollment

Secondary Outcomes (3)

• Time to hematologic response

  Up to 2 years from enrollment

• MRD Status

  At 6 months, 1 year and 2 years from treatment

• Relapse-Free Survival

  From start of treatment until 2 years

Study Arms (1)

Low dose Vemurafenib and Rituximab

EXPERIMENTAL

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.

Drug: Low dose vemurafenib plus rituximab

Interventions

Low dose vemurafenib plus rituximab DRUG

Vemurafenib 240 mg twice daily for 8 weeks with concurrent rituximab 375 mg/m2 every 2 weeks followed by maintenance consolidative rituximab 4 times every 2 weeks post-vemurafenib

Also known as: Vemurafenib, Rituximab

Low dose Vemurafenib and Rituximab

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age
• Histologically confirmed HCL that are BRAF V600E positive by IHC or NGS
• Patient's must meet the standard treatment initiation criteria, as defined by ANC ≤1.0, Hgb ≤ 10.0 or PLT ≤100K
• Patients can either have (1) not received any prior therapy for the disease or have had (2) failure to achieve any response to the initial purine analog-based therapy or (3) subsequent relapse after any prior therapy.
• ECOG performance status of 0-2
• Acceptable pre-study organ function during screening not exacerbated by Hairy Cell Leukemia. General thresholds should be a total bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN, and serum creatinine ≤ 1.5x ULN
• For women of childbearing potential, agreement to use acceptable methods of contraception
• For men with female partners of childbearing potential, agreement to use barrier contraception
• Negative serum pregnancy test within 7 days of commencement of treatment in premenopausal women.
• Ability to understand and willingness to sign a written informed consent document.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Pregnant or breast-feeding or intending to become pregnant during the study
• Have had chemotherapy (including purine analogs), rituximab, and other investigational agents within six weeks prior to entering the study. The patients cannot have received BRAF inhibitor therapy within 6 months of entering the study.
• Major surgery within 4 weeks prior to entering the study
• Invasive malignancy within the past 2 years prior to first study drug administration, except for adequately treated (with curative intent) basal or squamous cell carcinoma, melanoma, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer or other cancers from which the patient has been disease-free for at least 2 years
• Active HIV, hepatitis B and hepatitis C or any clinically significant history of liver disease. Hepatitis B prior infection is not a contraindication though will require therapy.
• Known hypersensitivity to any of the study drugs
• Patients with HCL that are BRAF V600E mutation negative

Sponsors & Collaborators

• Scripps Health: lead

Study Sites (1)

Scripps Cancer Center

La Jolla, California, 92037, United States

Location

Related Publications (2)

• Tiacci E, De Carolis L, Simonetti E, Capponi M, Ambrosetti A, Lucia E, Antolino A, Pulsoni A, Ferrari S, Zinzani PL, Ascani S, Perriello VM, Rigacci L, Gaidano G, Della Seta R, Frattarelli N, Falcucci P, Foa R, Visani G, Zaja F, Falini B. Vemurafenib plus Rituximab in Refractory or Relapsed Hairy-Cell Leukemia. N Engl J Med. 2021 May 13;384(19):1810-1823. doi: 10.1056/NEJMoa2031298.

  PMID: 33979489 BACKGROUND

• Grever M, Andritsos L, Banerji V, Barrientos JC, Bhat S, Blachly JS, Call T, Cross M, Dearden C, Demeter J, Dietrich S, Falini B, Forconi F, Gladstone DE, Gozzetti A, Iyengar S, Johnston JB, Juliusson G, Kraut E, Kreitman RJ, Lauria F, Lozanski G, Parikh SA, Park J, Polliack A, Ravandi F, Robak T, Rogers KA, Saven A, Seymour JF, Tadmor T, Tallman MS, Tam CS, Tiacci E, Troussard X, Zent C, Zenz T, Zinzani PL, Wormann B. Hairy cell leukemia and COVID-19 adaptation of treatment guidelines. Leukemia. 2021 Jul;35(7):1864-1872. doi: 10.1038/s41375-021-01257-7. Epub 2021 May 4.

  PMID: 33947938 BACKGROUND

MeSH Terms

Conditions

Leukemia, Hairy Cell

Interventions

Vemurafenib; Rituximab

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Alan Saven, MD

  Scripps Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2022
• First Posted: May 24, 2022
• Study Start: March 2, 2022
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)