OSI-TAR-766: Trial of Erlotinib in Patients With JAK-2 V617F Positive Polycythemia Vera

• Sponsor: University of Oklahoma (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01038856
• Collaborator: OSI Pharmaceuticals (Industry)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 50
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Polycythemia Vera	Drug: Erlotinib	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Erlotinib in Patients With JAK-2 V617F Positive Polycythemia Vera
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: +JAK2V61F mutation Patients with MPN diagnoses and polycythemia vera who also have a confirmed JAK2V617F mutation	Drug: 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; Other Names: Tarceva OSI-744

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate to Include Complete Hematological Response, Complete Molecular Response, Partial Hematological Response, and Minimal Hematological Response [Day 15]

Secondary Outcome Measures

1. 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

2. Improvement in Splenomegaly Size [4 months, end of treatment and 12 months end of treatment]

3. Decrease of Mutant JAK2V617F Allele Burden [every 2 months until end of treatment and 12 months after end of treatment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104

Sponsors and Collaborators

• University of Oklahoma
• OSI Pharmaceuticals

Investigators

• Principal Investigator: Mohamad Cherry, MD, University of Oklahoma

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Oklahoma
• ClinicalTrials.gov Identifier: NCT01038856
• Other Study ID Numbers: 2249
• First Posted: Dec 24, 2009
• Last Update Posted: Aug 24, 2020
• Last Verified: Aug 1, 2020

• Additional relevant MeSH terms: Polycythemia Vera; Polycythemia; Erlotinib Hydrochloride

Study Results

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 Detail	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.

Arm/Group Title	+JAK2V61F Mutation
Arm/Group Description	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
Period Title: Overall Study
STARTED	5
COMPLETED	3
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	+JAK2V61F Mutation
Arm/Group Description	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
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 20%
>=65 years	4 80%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%
Region of Enrollment (Count of Participants)
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate to Include Complete Hematological Response, Complete Molecular Response, Partial Hematological Response, and Minimal Hematological Response
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Single Arm Study
Arm/Group Description	This was a single arm study
Measure Participants	5
Number [participants]	0 0%

2. Secondary Outcome

Title	Incidence of Toxicities
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Erlotinib
Arm/Group Description	150 mg po daily x 16 weeks
Measure Participants	5
Count of Participants [Participants]	5 100%

3. Secondary Outcome

Title	Improvement in Splenomegaly Size
Time Frame	4 months, end of treatment and 12 months end of treatment

Outcome Measure Data

Analysis Population Description

no improvement in spleen size

Arm/Group Title	+JAK2V61F Mutation
Arm/Group Description	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
Measure Participants	3
Count of Participants [Participants]	0 0%

4. Secondary Outcome

Title	Decrease of Mutant JAK2V617F Allele Burden
Time Frame	every 2 months until end of treatment and 12 months after end of treatment

Outcome Measure Data

Analysis Population Description

did not achieve hematological response

Arm/Group Title	+JAK2V61F Mutation
Arm/Group Description	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
Measure Participants	3
Count of Participants [Participants]	0 0%

Adverse Events

Arm/Group Title	+JAK2V61F Mutation
Arm/Group Description	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
All Cause Mortality
	+JAK2V61F Mutation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	+JAK2V61F Mutation
	Affected / at Risk (%)	# Events
Total	1/5 (20%)
Gastrointestinal disorders
grade 3 colitis	1/5 (20%)	1
Skin and subcutaneous tissue disorders
grade 2 facial rash	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	+JAK2V61F Mutation
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Gastrointestinal disorders
Grade 1-2 Diarrhea	5/5 (100%)	5
Skin and subcutaneous tissue disorders
Rash	5/5 (100%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.