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)

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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.

Conditions
-----------------
Primary Myelofibrosis

Intervention / Treatment
-----------------
* Drug: Ruxolitinib


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib<br>All participants received ruxolitinib. | Drug: Ruxolitinib<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Primary Myelofibrosis, Hematologic Diseases, Myeloproliferative Disorders, INC424, Ruxolitinib