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Study With SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia

Primary Purpose

Hematopoietic Neoplasm

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SAR302503
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematopoietic Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Has had a diagnosis of hydroxyurea resistant or intolerant polycythemia vera (PV) or essential thrombocythemia (ET) documented at Screening.
  • Polycythemia vera or essential thrombocythemia defined according to the revised WHO criteria.
  • Polycythemia vera resistance or intolerance to hydroxyurea is defined as polycythemia vera patients on hydroxyurea with a hematocrit >45%, or phlebotomy twice in the last 6 months and at least once in the last 3 months.
  • Essential thrombocythemia resistance or intolerance to hydroxurea is defined as essential thrombocythemia patients on HU with platelet count >600 x 10x9/L.

Dose Expansion Phase (polycythemia vera) and 600 mg/day group (essential thrombocythemia):

  • Has had a diagnosis of polycythemia vera or essential thrombocythemia according to the revised WHO 2008 criteria.
  • PV patients must be resistant or intolerant to hydroxyurea.
  • ET patients must be resistant or intolerant to hydroxyurea.
  • Provide written informed consent to participate.

Exclusion criteria:

  • Less than 18 years of age.
  • Participation in any study of an investigational agent (drug, biologic, device) within 30 days prior to initiation of study drug, unless during non-treatment phase. (Prior treatment with another JAK2 inhibitor is allowed.)
  • Unwilling to comply with scheduled visits, treatment plans, laboratory assessments, and other study-related procedures.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 3 or 4 at study entry.
  • Splenectomy.
  • Active malignancy other than polycythemia vera or essential thrombocythemia, except adequately treated basal cell carcinoma and squamous cell carcinoma of the skin, cervical carcinoma in situ, or other malignancies that have been stable and off therapy for ≥5 years.
  • Major surgery within 28 days or radiation within 3 months prior to initiation of study drug.
  • Active acute infection requiring antibiotics.
  • Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness.
  • Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.
  • Any severe acute or chronic medical, neurological, or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with interpretation of study results and, in the Investigator's opinion, would make the patient inappropriate for entry into this study.
  • Inadequate organ function.
  • Known active (acute or chronic) Hepatitis A, B, or C; and Hepatitis B and C carriers.
  • Prior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis, non-alcoholic steatohepatitis [NASH]).
  • Concomitant treatment with or use of drugs or herbal agents known to be at least moderate inhibitors or inducers cytochrome P450 3A4 (CYP3A4).
  • Presence of any gastric or other disorder that would inhibit absorption of oral medication.
  • Known hypersensitivity to any excipients in the study drug formulation.
  • Women of childbearing potential, unless using effective contraception while on study drug.
  • Men who partner with a woman of childbearing potential, unless they agree to use effective contraception while on study drug.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sites / Locations

  • Investigational Site Number 840008
  • Investigational Site Number 840004
  • Investigational Site Number 840005
  • Investigational Site Number 840011
  • Investigational Site Number 840010
  • Investigational Site Number 840007
  • Investigational Site Number 840003
  • Investigational Site Number 840001
  • Investigational Site Number 036001
  • Investigational Site Number 036002
  • Investigational Site Number 036004
  • Investigational Site Number 036003
  • Investigational Site Number 124002
  • Investigational Site Number 124003
  • Investigational Site Number 124001
  • Investigational Site Number 250004
  • Investigational Site Number 250003
  • Investigational Site Number 250001
  • Investigational Site Number 276004
  • Investigational Site Number 276003
  • Investigational Site Number 380003
  • Investigational Site Number 380001
  • Investigational Site Number 380004
  • Investigational Site Number 410001
  • Investigational Site Number 410003
  • Investigational Site Number 410004
  • Investigational Site Number 410002
  • Investigational Site Number 724004
  • Investigational Site Number 724001
  • Investigational Site Number 724003
  • Investigational Site Number 724002
  • Investigational Site Number 826001
  • Investigational Site Number 826006
  • Investigational Site Number 826003
  • Investigational Site Number 826004

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

SAR302503 100 mg

SAR302503 200 mg

SAR302503 400 mg

SAR302503 600 mg

Arm Description

once daily X 28 days

once daily X 28 days

once daily X 28 days

once daily X 28 days

Outcomes

Primary Outcome Measures

Dose Ranging Phase: Proportion of PV patients with absence of phlebotomy and hematocrit below 45% and proportion of ET patients with a platelet count ≤ 400 x 10x9/L for a minimum of 3 months during the first 8 cycles of therapy.
PV Dose Expansion Phase: Proportion of PV patients with absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit.
ET Dose Ranging Phase (only 600 mg dose group): Proportion of ET patients with a platelet count ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit.

Secondary Outcome Measures

Proportion of PV patients with absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit through Cycle 8 (for PV dose expansion phase only).
Proportion of ET patients with platelet count ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Cycle 8.
Characterization of clinicohematologic response (CR, PR, and no Response) defined by European LeukemiaNet beginning at Day 1 of Cycle 6 visit through Cycle 8.
Percent change in spleen volume (per Magnetic Resonance Imaging (MRI)) at the end of Cycles 4 and 8 or end of treatment (EOT) relative to baseline.
Proportion of patients with a ≥ 35% reduction in spleen volume (per Magnetic Resonance Imaging (MRI)) at the end of Cycles 4 and 8 or end of treatment (EOT) relative to baseline.
Number of participants who have changes in histological, cytogenetic, and molecular responses in bone marrow.
Response (defined as either a 2-point improvement in or resolution of a symptom present at baseline) at the end of Cycles 1, 4, and 8 or end of treatment (EOT), as measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF).
Cumulative Distribution Function of responses between treatment groups at the end of Cycles 1, 4, and 8 or EOT on the MPN-SAF.
For each MPN-associated symptom present at baseline on the MPN-SAF, proportion of patients with resolution of that symptom at the end of Cycles 1, 4, and 8.
To measure generic health-related quality of life and utility values using the EQ-5D questionnaire after completion of 8 cycles of therapy.
Characterization of the safety profile of SAR302503, including the frequency, duration, and severity of adverse events graded using the National Cancer Institute (NCI) - CTCAE version 4.03, clinical laboratory parameters, ECG, and vital signs.

Full Information

First Posted
August 11, 2011
Last Updated
February 17, 2016
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT01420783
Brief Title
Study With SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia
Official Title
A Randomized Phase II, Open-Label Study of the Efficacy and Safety of Orally Administered SAR302503 in Patients With Polycythemia Vera (PV) or Essential Thrombocythemia (ET) Who Are Resistant or Intolerant to Hydroxyurea
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Primary Objective: Dose Ranging Phase: To evaluate the efficacy of daily oral doses of 100, 200, and 400 mg SAR302503 in patients with PV and ET who are resistant or intolerant to hydroxyurea (per European LeukemiaNet criteria) for : Inducing absence of phlebotomy and a hematocrit below 45% for a minimum of 3 months in patients with polycythemia vera, and Reduction of platelet count to ≤400 x 10x9/L for a minimum of 3 months in patients with essential thrombocythemia. PV Dose Expansion Phase and ET Dose Ranging Phase (only 600 mg dose group): To evaluate the efficacy of daily oral SAR302503 in patients with PV and ET who are resistant or intolerant to hydroxyurea (per European LeukemiaNet criteria) for: Inducing absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit in patients with PV, and Reduction of platelet count to ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit in patients with ET. Secondary Objectives: To evaluate the safety of SAR302503. To evaluate the efficacy of SAR302503 in patients with PV who are resistant or intolerant to hydroxyurea for inducing absence of phlebotomy eligibility. To evaluate the efficacy of SAR302503 in patients with ET who are resistant or intolerant to hydroxyurea for reduction of platelet counts. To evaluate the efficacy of SAR302503 in inducing complete and partial responses beginning at Day 1 of Cycle 6 visit through Cycle 8. To evaluate splenic response as measured by spleen volume using MRI or CT. To evaluate the pharmacokinetics of SAR302503 after single and repeat doses. To evaluate the pharmacodynamics of SAR302503 as measured by changes in JAK2V617F allele burden in patients with JAK2V617F mutation, and STAT3 phosphorylation inhibition. To measure improvement in baseline myeloproliferative neoplasm (MPN)-associated symptoms, as well as overall impact on quality of life. To measure generic health-related quality of life and utility value using the EuroQol Group (EQ-5DTM) questionnaire.
Detailed Description
The duration of the study for an individual patient is at least 40 weeks and will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of up to 8, 28-day cycles (32 weeks), and a follow-up visit 30 days following the last administration of study drug. Treatment may continue if the patient is deriving benefit and does not experience disease progression, unacceptable toxicity, or meet other study withdrawal criteria. Per Protocol Amendment No. 5, accrual of patients with essential thrombocythemia is closed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic Neoplasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
81 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SAR302503 100 mg
Arm Type
Experimental
Arm Description
once daily X 28 days
Arm Title
SAR302503 200 mg
Arm Type
Experimental
Arm Description
once daily X 28 days
Arm Title
SAR302503 400 mg
Arm Type
Experimental
Arm Description
once daily X 28 days
Arm Title
SAR302503 600 mg
Arm Type
Experimental
Arm Description
once daily X 28 days
Intervention Type
Drug
Intervention Name(s)
SAR302503
Intervention Description
Pharmaceutical form:capsule Route of administration: oral
Primary Outcome Measure Information:
Title
Dose Ranging Phase: Proportion of PV patients with absence of phlebotomy and hematocrit below 45% and proportion of ET patients with a platelet count ≤ 400 x 10x9/L for a minimum of 3 months during the first 8 cycles of therapy.
Time Frame
2 years
Title
PV Dose Expansion Phase: Proportion of PV patients with absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit.
Time Frame
2 years
Title
ET Dose Ranging Phase (only 600 mg dose group): Proportion of ET patients with a platelet count ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Proportion of PV patients with absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit through Cycle 8 (for PV dose expansion phase only).
Time Frame
2 years
Title
Proportion of ET patients with platelet count ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Cycle 8.
Time Frame
2 years
Title
Characterization of clinicohematologic response (CR, PR, and no Response) defined by European LeukemiaNet beginning at Day 1 of Cycle 6 visit through Cycle 8.
Time Frame
2 years
Title
Percent change in spleen volume (per Magnetic Resonance Imaging (MRI)) at the end of Cycles 4 and 8 or end of treatment (EOT) relative to baseline.
Time Frame
2 years
Title
Proportion of patients with a ≥ 35% reduction in spleen volume (per Magnetic Resonance Imaging (MRI)) at the end of Cycles 4 and 8 or end of treatment (EOT) relative to baseline.
Time Frame
2 years
Title
Number of participants who have changes in histological, cytogenetic, and molecular responses in bone marrow.
Time Frame
2 years
Title
Response (defined as either a 2-point improvement in or resolution of a symptom present at baseline) at the end of Cycles 1, 4, and 8 or end of treatment (EOT), as measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF).
Time Frame
2 years
Title
Cumulative Distribution Function of responses between treatment groups at the end of Cycles 1, 4, and 8 or EOT on the MPN-SAF.
Time Frame
2 years
Title
For each MPN-associated symptom present at baseline on the MPN-SAF, proportion of patients with resolution of that symptom at the end of Cycles 1, 4, and 8.
Time Frame
2 years
Title
To measure generic health-related quality of life and utility values using the EQ-5D questionnaire after completion of 8 cycles of therapy.
Time Frame
2 years
Title
Characterization of the safety profile of SAR302503, including the frequency, duration, and severity of adverse events graded using the National Cancer Institute (NCI) - CTCAE version 4.03, clinical laboratory parameters, ECG, and vital signs.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Has had a diagnosis of hydroxyurea resistant or intolerant polycythemia vera (PV) or essential thrombocythemia (ET) documented at Screening. Polycythemia vera or essential thrombocythemia defined according to the revised WHO criteria. Polycythemia vera resistance or intolerance to hydroxyurea is defined as polycythemia vera patients on hydroxyurea with a hematocrit >45%, or phlebotomy twice in the last 6 months and at least once in the last 3 months. Essential thrombocythemia resistance or intolerance to hydroxurea is defined as essential thrombocythemia patients on HU with platelet count >600 x 10x9/L. Dose Expansion Phase (polycythemia vera) and 600 mg/day group (essential thrombocythemia): Has had a diagnosis of polycythemia vera or essential thrombocythemia according to the revised WHO 2008 criteria. PV patients must be resistant or intolerant to hydroxyurea. ET patients must be resistant or intolerant to hydroxyurea. Provide written informed consent to participate. Exclusion criteria: Less than 18 years of age. Participation in any study of an investigational agent (drug, biologic, device) within 30 days prior to initiation of study drug, unless during non-treatment phase. (Prior treatment with another JAK2 inhibitor is allowed.) Unwilling to comply with scheduled visits, treatment plans, laboratory assessments, and other study-related procedures. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 3 or 4 at study entry. Splenectomy. Active malignancy other than polycythemia vera or essential thrombocythemia, except adequately treated basal cell carcinoma and squamous cell carcinoma of the skin, cervical carcinoma in situ, or other malignancies that have been stable and off therapy for ≥5 years. Major surgery within 28 days or radiation within 3 months prior to initiation of study drug. Active acute infection requiring antibiotics. Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness. Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug. Any severe acute or chronic medical, neurological, or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with interpretation of study results and, in the Investigator's opinion, would make the patient inappropriate for entry into this study. Inadequate organ function. Known active (acute or chronic) Hepatitis A, B, or C; and Hepatitis B and C carriers. Prior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis, non-alcoholic steatohepatitis [NASH]). Concomitant treatment with or use of drugs or herbal agents known to be at least moderate inhibitors or inducers cytochrome P450 3A4 (CYP3A4). Presence of any gastric or other disorder that would inhibit absorption of oral medication. Known hypersensitivity to any excipients in the study drug formulation. Women of childbearing potential, unless using effective contraception while on study drug. Men who partner with a woman of childbearing potential, unless they agree to use effective contraception while on study drug. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 840008
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259-5499
Country
United States
Facility Name
Investigational Site Number 840004
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Investigational Site Number 840005
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Investigational Site Number 840011
City
Palo Alto
State/Province
California
ZIP/Postal Code
94301
Country
United States
Facility Name
Investigational Site Number 840010
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0759
Country
United States
Facility Name
Investigational Site Number 840007
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Investigational Site Number 840003
City
St Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Investigational Site Number 840001
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Investigational Site Number 036001
City
Clayton
ZIP/Postal Code
3168
Country
Australia
Facility Name
Investigational Site Number 036002
City
Kingswood
ZIP/Postal Code
2747
Country
Australia
Facility Name
Investigational Site Number 036004
City
Kogarah
ZIP/Postal Code
2217
Country
Australia
Facility Name
Investigational Site Number 036003
City
Randwick
ZIP/Postal Code
2031
Country
Australia
Facility Name
Investigational Site Number 124002
City
Montreal
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Investigational Site Number 124003
City
Toronto
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Investigational Site Number 124001
City
Vancouver
ZIP/Postal Code
V6Z 1Y6
Country
Canada
Facility Name
Investigational Site Number 250004
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
Investigational Site Number 250003
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
Investigational Site Number 250001
City
Paris Cedex 10
ZIP/Postal Code
75475
Country
France
Facility Name
Investigational Site Number 276004
City
Frankfurt Am Main
ZIP/Postal Code
60590
Country
Germany
Facility Name
Investigational Site Number 276003
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
Investigational Site Number 380003
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Investigational Site Number 380001
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Facility Name
Investigational Site Number 380004
City
Orbassano
ZIP/Postal Code
10043
Country
Italy
Facility Name
Investigational Site Number 410001
City
Seongnam
ZIP/Postal Code
463-707
Country
Korea, Republic of
Facility Name
Investigational Site Number 410003
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Investigational Site Number 410004
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Investigational Site Number 410002
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Investigational Site Number 724004
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Investigational Site Number 724001
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Investigational Site Number 724003
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Investigational Site Number 724002
City
Valencia
Country
Spain
Facility Name
Investigational Site Number 826001
City
Belfast
ZIP/Postal Code
BT9 7AB
Country
United Kingdom
Facility Name
Investigational Site Number 826006
City
Birmingham
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Facility Name
Investigational Site Number 826003
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Facility Name
Investigational Site Number 826004
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom

12. IPD Sharing Statement

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Study With SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia

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