Polycythemia Vera
Conditions
Brief summary
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
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.
Interventions
DRUGErlotinib
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
Sponsors
OSI Pharmaceuticals
University of Oklahoma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Response Rate to Include Complete Hematological Response, Complete Molecular Response, Partial Hematological Response, and Minimal Hematological Response | Day 15 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Toxicities | First assessment at day 15, subsequent assessments at 28 day intervals for an average of 1 year | Grade 3 or grade 4 toxicities as measured by CTCAE v3.0 |
| 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 | — |
Countries
United States
Participant flow
Recruitment details
we conducted a single arm, prospective phase II study at the University of Oklahoma Health Sciences Center and the Oklahoma City VA hospitals in patients withWHO-defined JAK2V617F-positive PV from June 2010 to August 2012
Pre-assignment details
Patients were eligible for the study if they were at least 18 years of age and had a diagnosis of PV per WHO 2008 criteria. Additional eligibility criteria included adequate liver and kidney function tests and an ECOG performance status of 0, 1, 2, or 3.
Participants by arm
| Arm | Count |
|---|---|
| +JAK2V61F Mutation Patients with MPN diagnoses and polycythemia vera who also have a confirmed JAK2V617F mutation
Erlotinib: 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 | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | +JAK2V61F Mutation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 63 years |
| Region of Enrollment United States | 5 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
Overall Response Rate to Include Complete Hematological Response, Complete Molecular Response, Partial Hematological Response, and Minimal Hematological Response
Time frame: Day 15
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm Study | Overall Response Rate to Include Complete Hematological Response, Complete Molecular Response, Partial Hematological Response, and Minimal Hematological Response | 0 participants |
Secondary
Decrease of Mutant JAK2V617F Allele Burden
Time frame: every 2 months until end of treatment and 12 months after end of treatment
Population: did not achieve hematological response
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm Study | Decrease of Mutant JAK2V617F Allele Burden | 0 Participants |
Secondary
Improvement in Splenomegaly Size
Time frame: 4 months, end of treatment and 12 months end of treatment
Population: no improvement in spleen size
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm Study | Improvement in Splenomegaly Size | 0 Participants |
Secondary
Incidence of Toxicities
Grade 3 or grade 4 toxicities as measured by CTCAE v3.0
Time frame: First assessment at day 15, subsequent assessments at 28 day intervals for an average of 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm Study | Incidence of Toxicities | 5 Participants |