We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Low Dose Vemurafenib and Rituximab in Hairy Cell Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05388123
Recruitment Status : Recruiting
First Posted : May 24, 2022
Last Update Posted : May 24, 2022
Sponsor:
Information provided by (Responsible Party):
Scripps Health

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 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.

Condition or disease Intervention/treatment Phase
Hairy Cell Leukemia Drug: Low dose vemurafenib plus rituximab Phase 2

Detailed Description:
This is a single-center, open label, single arm, investigator-initiated phase II trial of the oral BRAF inhibitor, vemurafenib, plus rituximab in patients with previously untreated or relapsed and refractory HCL. 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 concomitantly with vemurafenib every 2 weeks from the first day of treatment. After completion of vemurafenib, the patient will receive rituximab 375 mg/m2 every 2 weeks for a total of 8 weeks. The entire duration of treatment will be 16 weeks. Six months after the initiation of the treatment, a peripheral blood flow cytometry and a bone marrow aspirate and biopsy will be performed for assessment of response and evaluation of minimal residual disease (MRD).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm Phase II Pilot Study of Low Dose Vemurafenib Plus Rituximab in the Front-line and Relapsed/Refractory Treatment of Hairy Cell Leukemia
Actual Study Start Date : January 1, 2022
Estimated Primary Completion Date : January 1, 2025
Estimated Study Completion Date : January 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: Low dose Vemurafenib and Rituximab
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
Vemurafenib 960 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
Other Names:
  • Vemurafenib
  • Rituximab




Primary Outcome Measures :
  1. Complete Response [ Time Frame: Up to 2 years from enrollment ]
    Resolution of cytopenias and splenomegaly


Secondary Outcome Measures :
  1. Time to hematologic response [ Time Frame: Up to 2 years from enrollment ]
    Days until resolution of cytopenias

  2. MRD Status [ Time Frame: At 6 months, 1 year and 2 years from treatment ]
    At the time of bone marrow assessment by testing for BRAFV600E mutation status

  3. Relapse-Free Survival [ Time Frame: From start of treatment until 2 years ]
    Reapperance of Hairy-Cell related cytopenia



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥ 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.

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05388123


Contacts
Layout table for location contacts
Contact: Alan Saven, MD 8585548788 saven.alan@scrippshealth.org
Contact: David J Hermel, MD 8585377617 hermel.david@scrippshealth.org

Locations
Layout table for location information
United States, California
Scripps MD Anderson Cancer Center Recruiting
La Jolla, California, United States, 92037
Contact: David J Hermel, MD    858-537-7617    hermel.david@scrippshealth.org   
Principal Investigator: Alan Saven, MD         
Sub-Investigator: David Hermel, MD         
Sponsors and Collaborators
Scripps Health
Publications:
Layout table for additonal information
Responsible Party: Scripps Health
ClinicalTrials.gov Identifier: NCT05388123    
Other Study ID Numbers: IRB-21-7787
First Posted: May 24, 2022    Key Record Dates
Last Update Posted: May 24, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Plan to publish aggregate data in manuscript

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Hairy Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Vemurafenib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action