Efficacy and Safety of Ruxolitinib in the Treatment of Anemic Myelofibrosis Patients.

NCT02966353 | Completed Phase 2 Results

• 1 other identifier: CINC424A2411
• Study Type: interventional
• Target: 51
• Locations: 11 countries
• Sites: 20

Brief Summary

This was a study of treatment with ruxolitinib in patients who presented with transfusion dependent or independent anemia. Starting dose was 10 mg BID. This dose was maintained for the first 12 weeks of the study and up-titrated thereafter unless the subject met criteria for dose hold or dose reduction

Conditions

Primary Myelofibrosis; Post-Polycythemia Vera-Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis

Keywords

Ruxolitinib; anemia; Primary Myelofibrosis; PMF; Post-Polycythemia Vera-Myelofibrosis; PPV-MF; Post-Essential Thrombocythemia Myelofibrosis; PET-MF; adult; INC424

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With at Least 50% Reduction in Spleen Length From Baseline at Week 24

  Percentage of participants achieving a 50% reduction in spleen length at week 24. For subjects with palpable spleen at baseline and non-palpable at post-baseline, the post-baseline spleen are imputed as 0. Subjects who had palpable, but missing spleen length at baseline is excluded from the analysis. Subjects with missing spleen length at Week 24 or who withdraw earlier from the study are considered as a non-responder. The 95% CI is computed using exact Clopper-Pearson method.

  Baseline up to week 24

Secondary Outcomes (5)

• Percentage of Participants With at Least 50% Reduction in Spleen Length From Baseline at Week 48

  Baseline up to week 48

• Percentage of Participants by Spleen Length Reduction or no Increase From Baseline Category at Week 24 and Week 48

  baseline, weeks 24 and 48

• Percentage of Participants With at Least a 50% Reduction in Myelofibrosis 7 Item Symptom Scale (MF-7) and Myelofibrosis Symptom Assessment Form (MFSAF) at Week 24

  Baseline and week 24

• Patient Global Impression of Change (PGIC) at Week 24 and Week 48

  Baseline up to week 48

• Percentage of Participants Transfusion Independency From Baseline up to Week 96

  Baseline up to week 96

Study Arms (1)

All Subjects

EXPERIMENTAL

10 mg BID (2 tablets of 5mg) was self-administered as starting dose for all patients. This dose was maintained for the first 12 weeks and titrated up thereafter unless they had met criteria for dose hold or dose reduction. Dose was to have been increased or decreased per standardized dosing paradigm and not to have exceeded 25 mg bid.

Drug: ruxolitinib

Interventions

ruxolitinib DRUG

Ruxolitinib was supplied in 5 mg tablets to be taken orally approximately 12 hours apart (morning and night)

All Subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained prior to any screening procedures.
• Male or female patients aged ≥ 18 years of age.
• Patients must have been diagnosed with PMF, according to the 2016 revised International Standard Criteria, PPV MF or PET-MF, irrespective of JAK2 mutation status.
• Patients must have had palpable splenomegaly that is equal to or greater than 5 cm below the left costal margin.
• Patients must have had hemoglobin less than 10 g/dL
• Patients must have had a history of transfusions must have a documented transfusion record in the previous 12 weeks to baseline.
• Patients must have had ECOG performance status of 0, 1, or 2.
• Patients must have had a peripheral blood blast percentage count of \< 10%.
• Patients must have recovered or stabilized sufficiently from any adverse drug reactions associated with prior treatments before beginning treatment with ruxolitinib.

You may not qualify if:

• Patients who had prior treatment with any JAK1 or JAK2 inhibitor.
• Patients who had known hypersensitivity to ruxolitinib or other JAK1/JAK2 inhibitors, or to their excipients.
• Patients who had been eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).
• Patients who had inadequate bone marrow reserve at baseline as demonstrated by at least one of the following:
• ANC that is ≤ 1,000/µL.
• Platelet count that is \<50,000/µL without the assistance of growth factors, thrombopoietic factors or platelet transfusions.
• Hemoglobin count that is ≤ 6.5 g/dL despite transfusions.
• Patients who had severely impaired renal function defined by: Creatinine clearance less than 30 mL/min.
• Patients who had inadequate liver function defined by any of these:
• Total bilirubin ≥ 2.5 x ULN and subsequent determination of direct bilirubin ≥ 2.5 x ULN;
• Alanine aminotransferase (ALT) \> 2.5 x ULN;
• Aspartate aminotransferase (AST) \> 2.5 x ULN.
• Patients who were being treated concurrently with a strong (potent) systemic inhibitor or inducer of CYP3A4 at the time of Screening.
• Presence of active bacterial, fungal, parasitic, or viral infection which requires therapy.
• Known history of human immunodeficiency virus (HIV) infection or other immunodeficiency syndromes such as X-linked agammaglobulinemia and common variable immune deficiency.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (20)

Novartis Investigative Site

Vienna, A-1090, Austria

Location

Novartis Investigative Site

Antwerp, 2060, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Sofia, 1413, Bulgaria

Location

Novartis Investigative Site

Sofia, 1756, Bulgaria

Location

Novartis Investigative Site

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Novartis Investigative Site

Halle S, 06120, Germany

Location

Novartis Investigative Site

Athens, GR, 115 27, Greece

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Florence, FI, 50134, Italy

Location

Novartis Investigative Site

Palermo, PA, 90127, Italy

Location

Novartis Investigative Site

Bunkyo Ku, Tokyo, 113-8431, Japan

Location

Novartis Investigative Site

Moscow, 125167, Russia

Location

Novartis Investigative Site

Moscow, 129110, Russia

Location

Novartis Investigative Site

Petrozavodsk, 185019, Russia

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

Location

Novartis Investigative Site

Alicante, Valencia, 03010, Spain

Location

Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Kocaeli, 41380, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Primary Myelofibrosis; Anemia

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2016
• First Posted: November 17, 2016
• Study Start: March 31, 2017
• Primary Completion: July 24, 2018
• Study Completion: February 15, 2019
• Last Updated: April 30, 2020
• Results First Posted: April 30, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (1); BE (2); AU (1); RU (3); ES (3); JP (1); IT (3); TU (2); GR (1); BU (2); CA (1)