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)

Primary Myelofibrosis Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02091752
• Other study ID #: CINC424A2407
• Status: Terminated
• Phase: Phase 2
• First received: March 6, 2014
• Last updated: January 5, 2016
• Start date: September 2014
• Est. completion date: February 2015

Study information

• Verified date: January 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: AGES (Bundesamt für Sicherheit im Gesundheitswesen)Brazil: ANVISA - Agência Nacional de Vigilância SanitáriaCanada: Health CanadaGermany: BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte)Italy: AIFA (Agenzia Italiana del Farmaco)Spain: Agencia Española de Medicamentos y Productos SanitariosThailand: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Primary Myelofibrosis

Intervention

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.

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Leipzig
Italy	Novartis Investigative Site	Firenze	FI
Spain	Novartis Investigative Site	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients Achieving =20% Reduction From Baseline in Spleen Volume		Week 24	No
Secondary	Proportion of Patients Achieving =35% Reduction From Baseline in Spleen Volume		Week 24	No
Secondary	Proportion of Patients Achieving =25% and =50% Reduction, Respectively From Baseline, in Spleen Length		Week 24	No
Secondary	Change From Baseline in Spleen Length and Spleen Volume		Baseline, Week 24	No
Secondary	Proportion of Patients Achieving =25% and =50% Reduction, Respectively, From Baseline in Total Symptom Score (MPN-SAF TSS)		Week 24	No
Secondary	Change From Baseline in MPN-SAF TSS Score		Baseline, Week 24	No
Secondary	Patient Global Impression of Change (PGIC) Score		Week 1, Week 24	No
Secondary	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	No