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A Phase II Study of the BRAF Inhibitor, Vemurafenib, Plus Obinutuzumab in Patients With Previously Untreated Classical Hairy Cell Leukemia

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ClinicalTrials.gov Identifier: NCT03410875
Recruitment Status : Recruiting
First Posted : January 25, 2018
Last Update Posted : August 6, 2019
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Yale University
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.


Condition or disease Intervention/treatment Phase
Hairy Cell Leukemia Leukemia Leukemia, Hairy Cell Drug: Vemurafenib Drug: Obinutuzumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of the BRAF Inhibitor, Vemurafenib, Plus Obinutuzumab in Patients With Previously Untreated Classical Hairy Cell Leukemia
Actual Study Start Date : February 9, 2018
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: Untreated Hairy Cell Leukemia
Participants with HCL with no prior treatment for the disease
Drug: Vemurafenib
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.

Drug: Obinutuzumab
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.




Primary Outcome Measures :
  1. Efficacy of vemurafenib in combination with obinutuzumab [ Time Frame: 16 weeks ]
    Efficacy as assessed by complete response (CR) rates of participants



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

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): NCT03410875


Contacts
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Contact: Jae Park, MD 212-639-4048 parkj6@mskcc.org
Contact: Martin Tallman, MD 212-639-3842 TallmanM@mskcc.org

Locations
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United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06511
Contact: Scott Huntington, MD, MPH, MsC    203-200-4363      
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Eric Winer, MD    617-632-6876      
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Jae Park, MD    212-639-4048    parkj6@mskcc.org   
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Dana-Farber Cancer Institute
Yale University
Investigators
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Principal Investigator: Jae Park, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03410875     History of Changes
Other Study ID Numbers: 17-513
First Posted: January 25, 2018    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
Leukemia
Hairy Cell Leukemia
BRAF
vemurafenib
obinutuzumab
Memorial Sloan Kettering Cancer Center
17-513

Additional relevant MeSH terms:
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Leukemia
Leukemia, Hairy Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Obinutuzumab
Vemurafenib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action