Trial of Erlotinib in Patients With JAK-2 V617F Positive Polycythemia Vera

Study Overview
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Brief Summary
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The primary objective of this study is to determine the overall response rate to erlotinib in patients with polycythemia vera (PV). Response rate will be assessed by improvement in the complete blood count, ultrasound of the spleen, and JAK2 molecular status. It is purposed in this study to explore a possible molecular targeting of the driving mechanism of PV.

Detailed Description
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This is a phase II open-label study. Patients will be screened for MPN diagnoses and patients with Polycythemia vera proven to have JAK2V617F mutation will be given the option to enroll. Consenting patients will take erlotinib daily for 16 weeks. Blood work and pharmacokinetics will be drawn for serum level monitoring. Doses will be administered according to side effects or held. First assessment will be at day 15 wth subsequent assessments at 28 day intervals. Non-responders will be taken off the study and managed according to standard of care. Patients who do respond will continue taking the therapy for a total of 12 months. Observation will be for a total of 12 months after finishing treatment. In addition to the clinical aspect of this study, there will be correlative studies where molecular response will be checked and its correlation with clinical response.

Official Title
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Phase II Trial of Erlotinib in Patients With JAK-2 V617F Positive Polycythemia Vera

Conditions
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Polycythemia Vera

Intervention / Treatment
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* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: WHO 2008 diagnosis of Polycythemia Vera Hemoglobin > 18.5 g/dl for men (16.5 g/dl for women) and presence of JAK2V617F mutation and either bone marrow trilineage myeloproliferation or subnormal serum erythropoietin level Patients may be on active treatment (phlebotomy, aspirin) ECOG performance status 0,1,2,or 3 Adequate hepatic function, adequate renal function Exclusion Criteria: Patient with active malignancy Patients with clinically significant cardiac disease within 1 year Opthalmologic or gastrointestinal abnormalities Concurrent cytoreductive therapy is not allowed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: +JAK2V61F mutation<br>Patients with MPN diagnoses and polycythemia vera who also have a confirmed JAK2V617F mutation | Drug: Erlotinib<br>* Erlotinib supplied as tablets; oral dose of erlotinib of 150 mg daily to be continued for 16 weeks. Responders will continue for up to 12 months, non-responders will cease taking erlotinib<br>* Other names: OSI-744;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate to Include Complete Hematological Response, Complete Molecular Response, Partial Hematological Response, and Minimal Hematological Response |  | Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Toxicities | Grade 3 or grade 4 toxicities as measured by CTCAE v3.0 | First assessment at day 15, subsequent assessments at 28 day intervals for an average of 1 year | 
| Improvement in Splenomegaly Size |  | 4 months, end of treatment and 12 months end of treatment | 
| Decrease of Mutant JAK2V617F Allele Burden |  | every 2 months until end of treatment and 12 months after end of treatment |