Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis (JAKARTA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01437787
First received: September 16, 2011
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

Primary Objective:

  • To evaluate the efficacy of daily oral doses of 400 mg or 500 mg of SAR302503 (Investigational Medicinal Product, IMP) compared to placebo in the reduction of spleen volume as determined by magnetic resonance imaging (MRI) (or computed tomography scan in patients with contraindications for MRI).

Secondary Objectives:

  • To evaluate the effect on Myelofibrosis (MF)-associated symptoms (key MF symptoms) as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary.
  • To evaluate the Overall Survival of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo.
  • To evaluate the Progression Free Survival of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo.
  • To evaluate the durability of splenic response.
  • To evaluate the safety of IMP.

Condition Intervention Phase
Hematopoietic Neoplasm
Drug: SAR302503
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study of SAR302503 in Patients With Intermediate-2 or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Response Rate (RR), defined as the proportion of patients who have a ≥35% reduction in volume of spleen size at the end of Cycle 6, and confirmed 4 weeks thereafter [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Symptom Response Rate (SRR): Proportion of patients with ≥50% reduction from baseline to the end of Cycle 6 in the total symptom score. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    This assessment will be conducted through the modified MFSAF diary, which will be completed during the week prior to Day 1 of each treatment cycle up to Cycle 6, and during the week prior to the end of Cycle 6.

  • OS (overall survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo. [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • PFS (progression free survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo. [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • Proportion of patients who have ≥25% reduction in volume of spleen size at end of Cycle 6, and confirmed 4 weeks thereafter. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Duration of spleen response, measured by MRI (or CT scan in patients with contraindications for MRI. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Clinical and laboratory events graded by the NCI CTCAE v4.03. [ Time Frame: approximately 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 289
Study Start Date: December 2011
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo comparator
once daily X 28 days, orally, empty stomach, approximately same time each day
Drug: Placebo

Pharmaceutical form:capsule

Route of administration: oral

Experimental: SAR302503 400 mg
once daily X 28 days, orally, empty stomach, approximately same time each day
Drug: SAR302503

Pharmaceutical form:capsule

Route of administration: oral

Experimental: SAR302503 500 mg
once daily X 28 days, orally, empty stomach, approximately same time each day
Drug: SAR302503

Pharmaceutical form:capsule

Route of administration: oral


Detailed Description:

The expected duration of a patient's treatment in this study is approximately 8 months, based on a maximum 28-day screening period, followed by a ≥6-month (6-cycle) treatment period, and an End Of Treatment (EOT) visit, which should be performed at least 30 days following the last administration of IMP or placebo.

Patients who continue to benefit clinically will be allowed to remain on IMP or placebo beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Diagnosis of Primary Myelofibrosis (MF) or Post-Polycythemia Vera MF or Post-Essential Thrombocythemia MF, according to the 2008 World Health Organization and International Working Group of Myelofibrosis Research and Treatment (IWG-MRT) criteria.
  • MF classified as high-risk or intermediate-risk level 2, as defined by modified IWG-MRT criteria (IPSS) (according to Cervantes F. et. al.; at screening).
  • Enlarged spleen, palpable at least 5 cm below costal margin.
  • At least 18 years of age.
  • Eastern Cooperative Oncology Group performance status of 0, 1, or 2 at study entry.
  • The following laboratory values within 14 days prior to the initiation of IMP or placebo:
  • Absolute Neutrophil Count (ANC) ≥1.0 x 10exp9/L
  • Platelet count ≥50 x 10exp9/L
  • Serum creatinine ≤1.5 x Upper Limit of Normal (ULN)
  • Serum amylase and lipase ≤1.5 x ULN

Exclusion criteria:

  • Splenectomy.
  • Any chemotherapy (eg, hydroxyurea), immunomodulatory drug therapy (eg, thalidomide, interferon-alpha), Anagrelide, immunosuppressive therapy, corticosteroids >10 mg/day prednisone or equivalent, or growth factor treatment (eg, erythropoietin), or hormones (eg, androgens, danazol) within 14 days prior to initiation of IMP or placebo; darbepoetin use within 28 days prior to initiation of IMP or placebo. Patients who have had exposure to hydroxyurea (eg, hydrea) in the past may be enrolled into the study as long as it has not been administered within 14 days prior to initiation of IMP or placebo.
  • Major surgery within 28 days or radiation within 6 months prior to initiation of IMP or placebo.
  • Prior treatment with a Janus Kinase 2 (JAK2) inhibitor.
  • Known active (acute or chronic) Hepatitis A, B, or C; and hepatitis B and C carriers
  • AST or ALT ≥2.5 x ULN
  • Total Bilirubin:
  • Exclude if ≥3.0 x ULN
  • Patients with total bilirubin between 1.5-3.0 x ULN must be excluded if the direct bilirubin fraction is ≥25% of the total
  • Prior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis, non-alcoholic steatohepatitis [NASH])

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01437787

  Show 101 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01437787     History of Changes
Other Study ID Numbers: EFC12153, 2011-001897-25, U1111-1121-7170
Study First Received: September 16, 2011
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Primary Myelofibrosis
Hematologic Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Site
Neoplasms

ClinicalTrials.gov processed this record on October 01, 2014