A Study of Vemurafenib and Obinutuzumab Compared to Cladribine and Rituximab in People With Hairy Cell Leukemia (HCL)

A Randomized, Multi-Center, Phase II Study of Vemurafenib Plus Obinutuzumab vs. Cladribine Plus Rituximab in Patients With Previously Untreated Hairy Cell Leukemia (HCL)

The researchers are doing this study to compare the safety of vemurafenib in combination with obinutuzumab to the standard of approach of cladribine in combination with rituximab. The researchers will look at which treatment causes fewer or milder side effects. Researchers think vemurafenib and obinutuzumab (non-chemotherapy drugs) may cause fewer side effects compared with the usual approach of chemotherapy drugs. They will also compare the two approaches to see which approach is more effective at eliminating cancer cells.

Study Overview

• Status: Recruiting
• Conditions: Hairy Cell Leukemia
• Intervention / Treatment: Drug: Vemurafenib; Drug: Obinutuzumab; Drug: Cladribine; Drug: Rituximab

• Study Type: Interventional
• Enrollment (Estimated): 86
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jae Park, MD; Phone Number: 646-608-3743; Email: parkj6@mskcc.org
• Study Contact Backup: Name: Mark Geyer, MD; Phone Number: 646-608-3745

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Dana Farber Cancer Institute
      • Contact: Eric Winer, MD; Phone Number: 617-632-6876
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Mayo Clinic Cancer Center
      • Contact: Sameer Parikh, M.B.B.S.; Phone Number: 507-218-0772
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering at Basking Ridge (All Protocol Activities)
      • Contact: Jae Park, MD; Phone Number: 646-608-3743
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Jae Park, MD; Phone Number: 646-608-3743
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Jae Park, MD; Phone Number: 646-608-3743
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Cancer Commack - Suffolk (Limited Protocol Activities)
      • Contact: Jae Park, MD; Phone Number: 646-608-3743
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (All Protocol Activities)
      • Contact: Jae Park, MD; Phone Number: 646-608-3743
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)
      • Contact: Jae Park, MD; Phone Number: 646-608-3743
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)
      • Contact: Jae Park, MD; Phone Number: 646-608-3743
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University
      • Contact: Michael Grever, MD; Phone Number: 614-293-3196
      • Principal Investigator: Michael Grever, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must be ≥ 18 years of age
• Histologically confirmed classical HCL by the enrolling institution
• Presence of BRAF V600E mutation as confirmed by PCR, NGS or immunohistochemistry. If patient is known to have negative BRAF mutation, repeat testing is advisable as well as discussion with the main study principal investigator.
• Has not received any prior therapy for the disease
• Patients who meet the standard treatment initiation criteria, as defined by ANC ≤1.0, Hgb ≤ 10.0 or PLT ≤100K
• ECOG performance status of 0 - 2

• Acceptable pre-study organ function during screening as defined as:

  • Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), except in patients with known Gilbert's syndrome who may be enrolled if direct bilirubin ≤ 3 x ULN);
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN; and
  • Serum creatinine ≤ 1.5x ULN
• Electrocardiogram (ECG) without evidence of clinically significant ventricular arrhythmias or ischemia as determined by the investigator and a rate-corrected QT interval (QTc, Bazett's formula) of < 480 msec
• For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of vemurafenib and cladribine, and 18 months after discontinuation of rituximab and obinutuzumab
• For men with female partners of childbearing potential, agreement to use a latex condom and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of vemurafenib
• Negative serum pregnancy test within 7 days of commencement of treatment in women of childbearing potential

Exclusion Criteria:

• Have had previous treatment for HCL, including purine analogs, vemurafenib, rituximab, obinutuzumab, and other investigational agents. Previous treatment with transfusions and other supportive care such as G-CSF and erythropoietin are allowed.
• Known hypersensitivity to any of the study drugs.
• Patients with known long QT syndrome or uncorrectable electrolyte abnormalities
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.

• Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibody

  ° Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody [HBcAb] and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly DNA testing and take HBV viral prophylaxis such as entecavir.

• Known infection with HIV or human T-cell leukemia virus 1 (HTLV-1)
• Active uncontrolled infection, e.g. persistent bacteremia, supplemental oxygen or pressor supports, etc.
• Live vaccination within 28 days of randomization
• Patients with concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of the skin, in situ cervical cancer, adequately treated stage I/II cancer from which the patient is current in complete remission, or any other cancer from which the patient has been disease free for five years
• Malabsorption syndrome or other condition that precludes enteral route of administration
• Patients with HCL variant (as defined by absence of expression of CD25)
• Pregnant or lactating, or intending to become pregnant during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vemurafenib plus Obinutuzumab; Patients assigned to the study arm will receive vemurafenib orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days) for a total of 4 cycles. Obinutuzumab will be administered concomitantly with vemurafenib starting at cycle 2 of treatment in cycles of 4 weeks. Obinutuzumab infusions will be administered on days 1, 8 and 15 during the cycle 2 and every 4 weeks during the cycle 3 and 4 of treatment.	Drug: Vemurafenib; Vemurafenib orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days) for a total of 4 cycles.; Drug: Obinutuzumab; Obinutuzumab will be administered concomitantly with vemurafenib starting at cycle 2 of treatment in cycles of 4 weeks.
Active Comparator: Standard treatment of Cladribine plus Rituximab; Patients assigned to the SOC arm will receive cladribine IV on days 1-5 concurrently with rituximab IV per week for 8 times, i.e., weekly x8 from day 1.	Drug: Cladribine; Cladribine IV on days 1-5 concurrently with rituximab.; Drug: Rituximab; Rituximab on days 1-5 concurrently with rituximab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidences of ≥ grade 3 treatment-related toxicities	per CTCAE v5.0 within first 6 months from the start of the treatment to account delayed toxicities of the treatments	within 6 months of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete remission	Response will be determined by the Consensus Resolution response criteria. Complete response (CR); A morphological absence of hairy cells in the blood and bone marrow; A normalization of any organomegaly and cytopenias	2 years
partial response	Partial response (PR) °A normalization of cytopenias °≥50% reduction in organomegaly and bone marrow hairy cells.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Jae Park, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2024
• Primary Completion (Estimated): September 9, 2027
• Study Completion (Estimated): September 9, 2027

Study Registration Dates

• First Submitted: August 13, 2024
• First Submitted That Met QC Criteria: August 15, 2024
• First Posted (Actual): August 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Rituximab; Obinutuzumab; Cladribine; Vemurafenib; 24-160
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Hairy Cell; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Amides; Indoles; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Purines; Nucleosides; Ribonucleosides; Antibodies, Monoclonal, Murine-Derived; Deoxyribonucleosides; Sulfonamides; Sulfones; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Deoxyadenosines; Rituximab; Vemurafenib; Cladribine; obinutuzumab
• Other Study ID Numbers: 24-160

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No