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)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02091752
• Collaborator: (none)
• Enrollment: 3
• Locations: 3
• Arm: 1
• Duration (Months): 5
• Patient Per Site: 1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Myelofibrosis	Drug: Ruxolitinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Achieving ≥20% Reduction From Baseline in Spleen Volume [Week 24]

Secondary Outcome Measures

1. Proportion of Patients Achieving ≥35% Reduction From Baseline in Spleen Volume [Week 24]

2. Proportion of Patients Achieving ≥25% and ≥50% Reduction, Respectively From Baseline, in Spleen Length [Week 24]

3. Change From Baseline in Spleen Length and Spleen Volume [Baseline, Week 24]

4. Proportion of Patients Achieving ≥25% and ≥50% Reduction, Respectively, From Baseline in Total Symptom Score (MPN-SAF TSS) [Week 24]

5. Change From Baseline in MPN-SAF TSS Score [Baseline, Week 24]

6. Patient Global Impression of Change (PGIC) Score [Week 1, Week 24]

7. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Leipzig		Germany	04103
2	Novartis Investigative Site	Firenze	FI	Italy	50134
3	Novartis Investigative Site	Madrid		Spain	28034

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02091752
• Other Study ID Numbers: CINC424A2407
• First Posted: Mar 19, 2014
• Last Update Posted: Mar 24, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Novartis Pharmaceuticals: Primary Myelofibrosis; Hematologic Diseases; Myeloproliferative Disorders; INC424; Ruxolitinib
• Additional relevant MeSH terms: Primary Myelofibrosis

Study Results

Participant Flow

Arm/Group Title	Ruxolitinib
Arm/Group Description	All participants received ruxolitinib.
Period Title: Overall Study
STARTED	3
COMPLETED	0
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Ruxolitinib
Arm/Group Description	All participants received ruxolitinib.
Overall Participants	3
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	68.00 (9.165)
Sex: Female, Male (Count of Participants)
Female	2 66.7%
Male	1 33.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The study was terminated early due to low enrollment. Analysis was not done.

Arm/Group Title	Ruxolitinib
Arm/Group Description	All participants received ruxolitinib.
Measure Participants	0

2. Secondary Outcome

Title	Proportion of Patients Achieving ≥35% Reduction From Baseline in Spleen Volume
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The study was terminated early due to low enrollment. Analysis was not done.

Arm/Group Title	Ruxolitinib
Arm/Group Description	All participants received ruxolitinib.
Measure Participants	0

3. Secondary Outcome

Title	Proportion of Patients Achieving ≥25% and ≥50% Reduction, Respectively From Baseline, in Spleen Length
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The study was terminated early due to low enrollment. Analysis was not done.

Arm/Group Title	Ruxolitinib
Arm/Group Description	All participants received ruxolitinib.
Measure Participants	0

4. Secondary Outcome

Title	Change From Baseline in Spleen Length and Spleen Volume
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The study was terminated early due to low enrollment. Analysis was not done.

Arm/Group Title	Ruxolitinib
Arm/Group Description	All participants received ruxolitinib.
Measure Participants	0

5. Secondary Outcome

Title	Proportion of Patients Achieving ≥25% and ≥50% Reduction, Respectively, From Baseline in Total Symptom Score (MPN-SAF TSS)
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The study was terminated early due to low enrollment. Analysis was not done.

Arm/Group Title	Ruxolitinib
Arm/Group Description	All participants received ruxolitinib.
Measure Participants	0

6. Secondary Outcome

Title	Change From Baseline in MPN-SAF TSS Score
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

The study was terminated early due to low enrollment. Analysis was not done.

Arm/Group Title	Ruxolitinib
Arm/Group Description	All participants received ruxolitinib.
Measure Participants	0

7. Secondary Outcome

Title	Patient Global Impression of Change (PGIC) Score
Time Frame	Week 1, Week 24

Outcome Measure Data

Analysis Population Description

The study was terminated early due to low enrollment. Analysis was not done.

Arm/Group Title	Ruxolitinib
Arm/Group Description	All participants received ruxolitinib.
Measure Participants	0

8. Secondary Outcome

Title	Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EuroQol (EQ)-5D-5L Scores
Time Frame	Baseline, Day 1, Week 8, Week 12, Week 16, Week 24

Outcome Measure Data

Analysis Population Description

The study was terminated early due to low enrollment. Analysis was not done.

Arm/Group Title	Ruxolitinib
Arm/Group Description	All participants received ruxolitinib.
Measure Participants	0

Adverse Events

Arm/Group Title	Ruxolitinib
Arm/Group Description	All participants received ruxolitinib.
All Cause Mortality
	Ruxolitinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ruxolitinib
	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)
Gastrointestinal disorders
CONSTIPATION	1/3 (33.3%)
Immune system disorders
CYTOKINE RELEASE SYNDROME	1/3 (33.3%)
Infections and infestations
LISTERIOSIS	1/3 (33.3%)
Renal and urinary disorders
RENAL FAILURE	1/3 (33.3%)
Other (Not Including Serious) Adverse Events
	Ruxolitinib
	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)
Blood and lymphatic system disorders
ANAEMIA	1/3 (33.3%)
Gastrointestinal disorders
ANAL HAEMORRHAGE	1/3 (33.3%)
ASCITES	1/3 (33.3%)
CONSTIPATION	1/3 (33.3%)
DIARRHOEA	1/3 (33.3%)
VARICES OESOPHAGEAL	1/3 (33.3%)
Hepatobiliary disorders
PORTAL VEIN THROMBOSIS	1/3 (33.3%)
Infections and infestations
CYSTITIS	1/3 (33.3%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/3 (33.3%)
ASPARTATE AMINOTRANSFERASE INCREASED	1/3 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.