NCT03410875

Brief Summary

This is a multi-center, open label, single arm, phase II trial of the oral BRAF inhibitor, vemurafenib, plus obinutuzumab in patients with previously untreated HCL. A Simon mini-max two-stage design will be employed to assess the efficacy of the combination treatment of vemurafenib and obinutuzumab. In the first stage of the protocol, 9 patients will be treated. If fewer than 6 CRs are seen among the first 9 patients, the study will be closed for lack of efficacy. If at least 7 patients respond to the treatment, then an additional 19 patients will be accrued to the second stage, for a total of 28 patients. Eligible patients will receive vemurafenib at a dose of 960mg 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 at 1000mg per day on days 1, 8 and 15 during the cycle 2 and 1000mg per day every 4 weeks during the cycle 3 and 4 of treatment. After the completion of the treatment (i.e. after 4 cycles), a bone marrow aspirate and biopsy will be performed for assessment of response and evaluation of minimal residual disease (MRD). In case of certain defined toxicities, dose reductions of vemurafenib by 50% (480mg b.i.d.) or interruptions of up to 15 days are permitted. If additional dose reduction is required, vemurafenib may be reduced to 240mg oral b.i.d.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
8mo left

Started Feb 2018

Longer than P75 for phase_2

Geographic Reach
1 country

9 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress93%
Feb 2018Jan 2027

First Submitted

Initial submission to the registry

January 19, 2018

Completed
6 days until next milestone

First Posted

Study publicly available on registry

January 25, 2018

Completed
15 days until next milestone

Study Start

First participant enrolled

February 9, 2018

Completed
8.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2027

Last Updated

February 12, 2026

Status Verified

February 1, 2026

Enrollment Period

8.9 years

First QC Date

January 19, 2018

Last Update Submit

February 10, 2026

Conditions

Hairy Cell LeukemiaLeukemiaLeukemia, Hairy Cell

Keywords

LeukemiaHairy Cell LeukemiaBRAFvemurafenibobinutuzumabMemorial Sloan Kettering Cancer Center17-513

Outcome Measures

Primary Outcomes (1)

  • Efficacy of vemurafenib in combination with obinutuzumab

    Efficacy as assessed by complete response (CR) rates of participants

    16 weeks

Study Arms (1)

Untreated Hairy Cell Leukemia

EXPERIMENTAL

Participants with HCL with no prior treatment for the disease

Drug: VemurafenibDrug: Obinutuzumab

Interventions

VemurafenibDRUG

Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days) for a total of 4 cycles. In case of certain defined toxicities, dose reductions of vemurafenib by 50% (480mg b.i.d.) or interruptions of up to 15 days are permitted. If additional dose reduction is required, vemurafenib may be reduced to 240mg oral b.i.d.

Untreated Hairy Cell Leukemia
ObinutuzumabDRUG

Obinutuzumab will be administered concomitantly with vemurafenib starting at cycle 2 of treatment in cycles of 4 weeks. Obinutuzumab infusions will be administered at 1000mg per day on days 1, 8 and 15 during the cycle 2 and 1000mg per day every 4 weeks during the cycle 3 and 4 of treatment.

Untreated Hairy Cell Leukemia

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must be \>/= 18 years of age
  • Histologically confirmed classical HCL by the enrolling institution
  • 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)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \</=2.5x ULN
  • 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 (QT 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
  • 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 with 7 days of commencement of treatment in women of childbearing potential

You may not qualify if:

  • Have had previous treatment for HCL, including purine analogs, rituximab, 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
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
  • Patients with uncorrectable electrolyte abnormalities with potassium (K) \>ULN (upper limit of normal).
  • Patients with any active and uncontrolled infections (such as bacterial, fungal, and new or reactivated viral infections)
  • Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibody.
  • Patients who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation.
  • 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.
  • Known infection with HIV or human T-cell leukemia virus 1 (HTLV-1)
  • Invasive malignancy that require active systemic chemotherapy or biologics that may cause significant drug-drug interaction with either vemurafenib or obinutuzumab
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Yale University

New Haven, Connecticut, 06511, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Publications (1)

  • Park JH, Devlin S, Durham BH, Winer ES, Huntington S, von Keudell G, Vemuri S, Shukla M, Falco V, Cuello B, Gore S, Stone R, Abdel-Wahab O, Tallman MS. Vemurafenib and Obinutuzumab as Frontline Therapy for Hairy Cell Leukemia. NEJM Evid. 2023 Oct;2(10):EVIDoa2300074. doi: 10.1056/EVIDoa2300074. Epub 2023 Sep 21.

    PMID: 38320179DERIVED

Related Links

MeSH Terms

Conditions

Leukemia, Hairy CellLeukemia

Interventions

Vemurafenibobinutuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

SulfonamidesAmidesOrganic ChemicalsSulfonesSulfur CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Jae Park, MD

    Memorial Sloan Kettering Cancer Center

    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

January 19, 2018

First Posted

January 25, 2018

Study Start

February 9, 2018

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

January 1, 2027

Last Updated

February 12, 2026

Record last verified: 2026-02

Locations

US(9)