A Phase II Study of Re-treatment of Myelofibrosis Patients With Ruxolitinib/Jakavi After Treatment Interruption Due to Loss of Response and/or Adverse Event (ReTreatment Trial)

The ReTreatment Trial: A Phase II, Open-label, Single-arm Study of Re-treating Myelofibrosis Patients With Ruxolitinib/Jakavi After Treatment Interruption Due to Loss of Response and/or Adverse Event.

The aim of the study is to assess the efficacy and safety of restarting ruxolitinib after treatment interruption due to loss of response and/or adverse events.

Study Overview

• Status: Terminated
• Conditions: Primary Myelofibrosis
• Intervention / Treatment: Drug: Ruxolitinib

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
• Italy
  • FI
    • Firenze, FI, Italy, 50134
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28034
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of PMF, PPV MF or PET-MF, irrespective of JAK2 mutational status according to the 2008 revised International Standard Criteria
• Peripheral blast count < 10%
• Requires therapy for MF in the opinion of the investigator
• Received prior monotherapy treatment with ruxolitinib for at least 12 consecutive weeks and experienced treatment interruption because of lossof response or adverse event
• Patients adhering to the Screening phase assessments and undergoing a a ruxolitinib-free washout period of a minimum of 1 week and a maximum of 8 weeks
• ECOG performance status 0, 1, 2, or 3
• Adequate bone marrow function
• Written informed consent

Exclusion Criteria:

• Patients not initially responding (primary resistance) to ruxolitinib therapy
• Patients who underwent a splenectomy or spleen radiation
• Patients currently scheduled for bone marrow transplant
• Patients who have discontinued ruxolitinib < 14 days prior to screening
• Patients who are not able to receive a starting dose of ruxolitinib of at least 15 mg total daily dose
• Leukemic transformation
• Inadequate renal function
• Presence of clinically meaningful active bacterial, fungal, parasitic or viral infection which requires therapy
• Previous history of Progressive Multifocal Leuko-encephalopathy (PML)
• Clinically significant cardiac disease or significant concurrent medical condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ruxolitinib; All participants received ruxolitinib.

Drug: Ruxolitinib; Starting dose was based on reason for previous discontinuation of ruxolitinib (i.e. loss of response or AE) and baseline platelet count. For participants who previously discontinued ruxolitinib due to loss of response, the starting dose was determined based on baseline platelet counts as follows: participants with a baseline platelet count of ≥ 200 x 109/L began dosing at 20 mg po bid; participants with a baseline platelet count of 100 x 109/L to <200 x 109/L began dosing at 15 mg po bid. Participants who previously discontinued ruxolitinib due to an AE initiated therapy at a total daily dose 5 mg lower than the total daily dose prior to discontinuation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Patients Achieving ≥20% Reduction From Baseline in Spleen Volume	Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of Patients Achieving ≥35% Reduction From Baseline in Spleen Volume	Week 24
Proportion of Patients Achieving ≥25% and ≥50% Reduction, Respectively From Baseline, in Spleen Length	Week 24
Change From Baseline in Spleen Length and Spleen Volume	Baseline, Week 24
Proportion of Patients Achieving ≥25% and ≥50% Reduction, Respectively, From Baseline in Total Symptom Score (MPN-SAF TSS)	Week 24
Change From Baseline in MPN-SAF TSS Score	Baseline, Week 24
Patient Global Impression of Change (PGIC) Score	Week 1, Week 24
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EuroQol (EQ)-5D-5L Scores	Baseline, Day 1, Week 8, Week 12, Week 16, Week 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: March 6, 2014
• First Submitted That Met QC Criteria: March 17, 2014
• First Posted (Estimate): March 19, 2014

Study Record Updates

• Last Update Posted (Estimate): March 24, 2016
• Last Update Submitted That Met QC Criteria: February 24, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Ruxolitinib; Hematologic Diseases; INC424; Primary Myelofibrosis; Myeloproliferative Disorders
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis
• Other Study ID Numbers: CINC424A2407