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Trial details
Platform Study of Novel Ruxolitinib Combinations in Myelofibrosis Patients
Current status:
Approved
|
Date registered:
06/06/2022
Trial version(s)
History: 14/02/2022
History: 14/02/2022
History: 14/02/2022
Current: 14/02/2022
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2022035001
Protocol number
CINC424H12201
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
Primary sponsor
Novartis Pharmaceuticals
Primary sponsor: Country of origin
Novartis Pharmaceuticals
Public title
Platform Study of Novel Ruxolitinib Combinations in Myelofibrosis Patients
Acronym
ADORE
Scientific title
A Randomized, Open-label, Phase I/II Open Platform Study Evaluating Safety and Efficacy of Novel Ruxolitinib Combinations in Myelofibrosis Patients
Acronym
Brief summary of the study: English
The purpose of this study is to investigate the safety, pharmacokinetics and preliminary efficacy of combinations treatment of ruxolitinib with 5 novel compounds: siremadlin, crizanlizumab, sabatolimab, LTT462 and NIS793 in myelofibrosis (MF) subjects.
Brief summary of the study: Arabic
دراسة لتقييم سلامة وفعاليّة استعمالات روكسوليتينيب مع أدوية جديدة لدى مرضى التليّف النقويّ
Health conditions/problem studied: Specify
Myelofibrosis
Interventions: Specify
- Drug: Ruxolitinib 5 mg tablets for oral use Other Name: INC424, Jakavi - Drug: Siremadlin 10 mg, 20 mg, or 40 mg capsules for oral use Other Name: HDM201 - Drug: Crizanlizumab 100 mg/mL concentrate for infusion for intravenous use Other Name: SEG101 - Drug: Sabatolimab 100 mg/mL or 400 mg/4 mL concentrate for infusion for intravenous use Other Name: MBG453 - Drug: LTT462 100 mg capsule for oral use - Drug: NIS793 700 mg/7 mL concentrate for intravenous use
Key inclusion and exclusion criteria: Inclusion criteria
- Subjects have diagnosis of primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) criteria, or diagnosis of post-essential thrombocythemia (ET) (PET-MF) or post-polycythemia vera (PV) myelofibrosis (PPV-MF) according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) 2007 criteria - Palpable spleen of at least 5 cm from the left costal margin (LCM) to the point of greatest splenic protrusion or enlarged spleen volume of at least 450 cm3 per MRI or CT scan at baseline (a MRI/CT scan up to 8 weeks prior to first dose of study treatment can be accepted). - Have been treated with ruxolitinib for at least 24 weeks prior to first dose of study treatment - Are stable (no dose adjustments) on the prescribed ruxolitinib dose (between 5 and 25 mg twice a day (BID)) for ≥ 8 weeks prior to first dose of study treatment
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
99
Key inclusion and exclusion criteria: Exclusion criteria
- Not able to understand and to comply with study instructions and requirements. - Received any investigational agent for the treatment of MF (except ruxolitinib) within 30 days of first dose of study treatment or within 5 half-lives of the study treatment, whichever is greater - Peripheral blood blasts count of > 10%. - Received a monoclonal antibody (Ab) or immunoglobulin-based agent within 1 year of screening, or has documented severe hypersensitivity reactions/immunogenicity (IG) to a prior biologic - Splenic irradiation within 6 months prior to the first dose of study drug - Received blood platelet transfusion within 28 days prior to first dose of study treatment.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Randomized controlled trial
Study design: Masking
Open (masking not used)
Study design: Control
Active
Study phase
1 to 2
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
No
Name of IMP
Ruxolitinib
Type of IMP
Immunological
Pharmaceutical class
Janus Associated Kinase Inhibitor
Therapeutic indication
Myelofibrosis
Therapeutic benefit
progression free survival (PFS)
Biospecimen retention
Samples without DNA
Biospecimen description
Samples will be shipped to Covance Central Lab
Target sample size
4
Actual enrollment target size
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
28/04/2022
Date of study closure: Type
Anticipated
Date of study closure: Date
16/01/2024
Recruitment status
Pending
Date of completion
IPD sharing statement plan
Yes
IPD sharing statement description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Additional data URL
https://clinicaltrials.gov/ct2/show/record/NCT04097821?term=CINC424H12201&draw=2&rank=1
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Clinicaltrials.gov
NCT04097821
Sources of Monetary or Material Support
Name
Novartis Pharmaceuticals
Secondary Sponsors
Name
N/A
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Ali
Taher
Beirut
Lebanon
+9613755669
ataher@aub.edu.lb
American University of Beirut Medical Center
Scientific
Hind
Khairallah
KFF Healthcare - Khalil Fattal et fils
Lebanon
+961 1512002 #271
Hind.Khairallah@ fattal.com.lb
Khalil Fattal et Fils Sal
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
American University of Beirut Medical Center
Ali Taher
Hematology-Oncology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
American University of Beirut Medical Center
24/01/2022
Fuad Ziyadeh
fz05@aub.edu.lb
+961 (0) 1 350 000 ext:5445
Countries of Recruitment
Name
Australia
Belgium
Canada
Denmark
Germany
Hungary
Italy
Netherlands
Russian Federation
Spain
Sweden
Switzerland
United Kingdom
Lebanon
Health Conditions or Problems Studied
Condition
Code
Keyword
Myelofibrosis
Other specified diseases of blood and blood-forming organs (D75.8)
Myelofibrosis
Interventions
Intervention
Description
Keyword
Consenting, IMP administration
Consenting, IMP administration
Consenting, IMP administration
Primary Outcomes
Name
Time points
Measure
Incidence of dose limiting toxicities within the first 2 cycles
Baseline to the end of Cycle 2 (6 or 8 weeks)
Incidence and severity of dose limiting toxicities within the first 2 cycles (6 or 8 weeks) in Part 1 of the study
Response rate at the end of cycle 6 or cycle 8
Baseline to the end of Cycle 6 or 8 (24 weeks)
Composite of anemia improvement (hemoglobin level) and no spleen volume progression and no symptom worsening in Part 2 and Part 3 of the study. For a subject to be considered a responder, all three components of the composite have to be fulfilled
Key Secondary Outcomes
Name
Time points
Measure
Proportion of subjects achieving an improvement in hemoglobin level of ≥ 1.5 g/dL from baseline
Baseline to the end of Cycle 6 or 8 (24 weeks), and end of Cycle 12 or 16 (48 weeks)
Proportion of subjects achieving an improvement in hemoglobin level of at least >= 1.5 g/dL from baseline at each time point in Part 2 and Part 3 of the study.
Proportion of subjects achieving an improvement in hemoglobin level of at least >= 2.0 g/dL from baseline
Baseline to the end of Cycle 6 or 8 (24 weeks), and end of Cycle 12 or 16 (48 weeks)
Proportion of subjects achieving an improvement in hemoglobin level of at least >= 2.0 g/dL from baseline at each time point in Part 2 and Part 3 of the study
Change in spleen length from baseline
Baseline to day 1 and day 15 of Cycle 1, 2 and 3, day 1 of all subsequent cycles, and the end of 12 or 16 cycles (48 weeks)
Change in spleen length measured in centimeters by manual palpation summarized at each time point using descriptive statistics in Part 2 and Part 3 of the study
Change in spleen volume from baseline
Baseline to the end of Cycle 6 or 8 (24 weeks), the end of Cycle 12 or 16 (48 weeks) and at the end of treatment if not performed in the past 12 weeks (up to 48 weeks)
Change in spleen volume measured by magnetic resonance imaging (MRI) or computed tomography (CT) summarized at each time point using descriptive statistics, in Part 2 and Part 3 of the study
Change in symptoms of MFSAF v4.0 from baseline
Baseline to day 1 of Cycle 1, day 1 of all subsequent cycles of treatment (each cycle is 28 days except for arms containing NIS793, which are 21 days), as well as the end of treatment visit (approximately 52 weeks)
Change in total symptom scores (TSS) assessed by the Myelofibrosis (MF Symptom Assessment Form version 4.0 (MFSAF v4.0) at each time point in Part 2 and Part 3 of the study. The MFSAF v4.0 questionnaire focuses on the 7 core symptoms of MF: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety and bone pain. Subjects record symptom severity at it worst for each of the 7 symptoms on an 11-point numeric rating scale, from 0 (absent) to 10 (worst imaginable). The Total Symptom Score (TSS) is the sum of all the scores for all 7 symptoms.
Change in symptoms of EORTC QLQ-C30 from baseline
Baseline to day 1 of Cycle 1, day 1 of all subsequent cycles of treatment (each cycle is 28 days except for arms containing NIS793, which are 21 days), as well as the end of treatment visit (approximately 52 weeks)
Change in symptom scores assessed by European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ C-30) at each time point in Part 2 and Part 3 of the study. The EORTC QLQ-C30 includes 5 functional scales (physical, emotional, social, role, cognitive), eight symptom scales (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia, dyspnea, and appetite loss), as well as global health/quality-of-life and financial impact. Subjects respond according to the past week recall period, with the exception of the first 5 questions that represent physical functioning and capture the subject's current status. Raw scores are linearly converted to a 0-100 scale. For functional and global health status/QoL higher scores indicate better QoL and level of functioning; for symptom scales, higher scores indicate greater level of symptoms or difficulties.
Progression free survival, per progressive splenomegaly, accelerated phase, deteriorating cytopenia, leukemic transformation or death from any cause
Baseline to disease progression, which is up to 24 weeks for Part 1 or through study completion, an average of 1 year, for Part 2 and Part 3
Progressive splenomegaly is assessed by increasing spleen volume (by MRI/CT) of ≥ 25% from baseline. Accelerated phase: a circulating peripheral blood blast content of > 10% but < 20% confirmed after 2 weeks. Deteriorating cytopenia (dCP) independent from treatment defined for all patients by platelet count < 35 x10^9/L or neutrophil count < 0.75 x 10^9/L that lasts for at least 4 weeks. Leukemic transformation, a peripheral blood blast content of ≥ 20% associated with an absolute blast count of ≥ 1x10^9/L that lasts for at least 2 weeks or a bone marrow blast count of ≥ 20%.
Proportion of subjects achieving an impovement in bone marrow fibrosis of ≥ 1 grade from baseline
Baseline to the end of Cycle 6 or 8 (24 weeks), the end of Cycle 12 or 16 (48 weeks) and at the end of treatment if not performed in the past 12 weeks (up to 48 weeks)
Proportion of subjects achieving an improvement in bone marrow fibrosis of >= 1 grade at each time point will be summarized in Part 2 and Part 3 of the study.
Area under the Plasma Concentration versus Time Curve (AUC)
Days 1 and 5 of Cycle 1 and 2 for siremadlin and ruxolitinib, and Cycle 1 and Cycle 3 for crizanlizumab, sabatolimab and NIS793, and Days 1 and 15 of Cycle 1 for LTT462
AUC for each investigational drug in Part 1, Part 2 and Part 3 of the study
Maximum (peak) observed plasma drug concentration (Cmax)
Days 1 and 5 of Cycle 1 and 2 for siremadlin and ruxolitinib, and Cycle 1 and Cycle 3 for crizanlizumab, sabatolimab and NIS793, and Days 1 and 15 of Cycle 1 for LTT462
Cmax for each investigational drug in Part 1, Part 2 and Part 3 of the study
Time to reach maximum (peak) plasma, blood, serum or other body fulid drug concentration after single dose administration (Tmax)
Days 1 and 5 of Cycle 1 and 2 for siremadlin and ruxolitinib, and Cycle 1 and Cycle 3 for crizanlizumab, sabatolimab and NIS793, and Days 1 and 15 of Cycle 1 for LTT462
Tmax for each investigational drug in Part 1, Part 2 and Part 3 of the study
Concentration versus time profile
Days 1 and 5 of Cycle 1 and 2 for siremadlin and ruxolitinib, and Cycle 1 and Cycle 3 for crizanlizumab, sabatolimab and NIS793, and Days 1 and 15 of Cycle 1 for LTT462
Concentration versus time profile for each investigational drug in Part 1, Part 2 and Part 3 of the study
Presence and/or concentration of anti-drug antibody
Baseline to 105 days after last study drug administration for crizanlizumab, to 150 days after last study drug administration for sabatolimab, or to 90 days after last study drug administration for NIS793
The presence and titer of anti-drug antibodies for crizanlizumab, sabatolimab and NIS793 in Part 1, Part 2 and Part 3 of the study
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
PA06_IRB Approval_AUBMC
06/05/2022
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