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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04576156




Registration number
NCT04576156
Ethics application status
Date submitted
18/09/2020
Date registered
6/10/2020

Titles & IDs
Public title
A Study Comparing Imetelstat Versus Best Available Therapy for the Treatment of Intermediate-2 or High-risk Myelofibrosis (MF) Who Have Not Responded to Janus Kinase (JAK)-Inhibitor Treatment
Scientific title
A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat (GRN163L) Versus Best Available Therapy (BAT) in Patients with Intermediate-2 or High-risk Myelofibrosis (MF) Relapsed / Refractory (R/R) to Janus Kinase (JAK) Inhibitor
Secondary ID [1] 0 0
2020-003288-24
Secondary ID [2] 0 0
MYF3001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Imetelstat
Treatment: Drugs - Best Available Therapy (BAT)

Experimental: Imetelstat - Participants will receive imetelstat sodium at 9.4 mg/kg intravenous (IV) every 21 days (±3 days), until disease progression or unacceptable toxicity, treatment discontinuation or study end.

Active comparator: Best Available Therapy (BAT) - Participants will receive BAT (investigator-selected non-JAK-inhibitor treatment), until disease progression or unacceptable toxicity, treatment discontinuation or study end.

Participants on BAT who meet protocol-defined criteria for progressive disease may crossover to receive imetelstat treatment after sponsor's approval.


Treatment: Drugs: Imetelstat
Imetelstat sodium will be given intravenously at 9.4 mg/kg every 21 days, until disease progression or unacceptable toxicity, treatment discontinuation or study end.

Treatment: Drugs: Best Available Therapy (BAT)
Non-JAK-inhibitor treatment will be given, which may include but is not limited to hydroxyurea, thalidomide or an analog of thalidomide, interferon, danazol, hypomethylating agents, chemotherapy or radiotherapy.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival (OS)
Timepoint [1] 0 0
Baseline (Day 1) until End of Study (EOS) (approximately 3 years )]
Secondary outcome [1] 0 0
Symptom response rate
Timepoint [1] 0 0
Baseline (Day 1), and at Week 24
Secondary outcome [2] 0 0
Progression-free survival
Timepoint [2] 0 0
Baseline (Day 1) until End of Study (EOS) (approximately 3 years)
Secondary outcome [3] 0 0
Spleen response rate
Timepoint [3] 0 0
Baseline (Day 1), and at Week 24
Secondary outcome [4] 0 0
Complete remission (CR), partial remission (PR), clinical improvement (CI), spleen response, symptoms response, and anemia response per modified 2013 IWG-MRT criteria
Timepoint [4] 0 0
Baseline (Day 1) until End of Treatment (approximately 3 years)
Secondary outcome [5] 0 0
Reduction in the degree of bone marrow fibrosis
Timepoint [5] 0 0
Baseline (Day 1) until End of Treatment (approximately 3 years)
Secondary outcome [6] 0 0
Number of Participants with Adverse Events
Timepoint [6] 0 0
Screening (Day -28 to -1) until End of Study (approximately 3 years)
Secondary outcome [7] 0 0
Assessment of Cmax
Timepoint [7] 0 0
Day 1 of all cycles (each cycle is 21 days)
Secondary outcome [8] 0 0
Assessment of Tmax
Timepoint [8] 0 0
Day 1 of all cycles (each cycle is 21 days)
Secondary outcome [9] 0 0
Assessment of t1/2
Timepoint [9] 0 0
Day 1 of all cycles (each cycle is 21 days)
Secondary outcome [10] 0 0
Assessment of AUC
Timepoint [10] 0 0
Day 1 of all cycles (each cycle is 21 days)
Secondary outcome [11] 0 0
European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30) scores
Timepoint [11] 0 0
Baseline to End of Study (approximately 3 years)
Secondary outcome [12] 0 0
EuroQol-EQ-5D (EQ-5D-5L) questionnaire scores
Timepoint [12] 0 0
Baseline to End of Study (approximately 3 years)

Eligibility
Key inclusion criteria
* Diagnosis of primary myelofibrosis according to the revised World Health Organization criteria or post-essential thrombocythemia-MF or post-polycythemia vera-MF according to the IWG-MRT criteria
* Dynamic International Prognostic Scoring System intermediate-2 or high-risk MF
* Relapsed/refractory to JAK-inhibitor treatment as defined in either inclusion (i), (ii) or (iii) and not eligible for allogeneic stem cell transplantation (ASCT) at screening:

* (i) Treatment with JAK-inhibitor for >= 6 months duration, including at least 2 months at an optimal dose as assessed by the investigator for that participant and at least one of the following:

1. no decrease in spleen volume (< 10% by MRI or CT) from the start of treatment with JAK-inhibitor
2. no decrease in spleen size (< 30% by palpation or length by imaging) from the start of treatment with JAK-inhibitor
3. no decrease in symptoms (< 20% by Myelofibrosis Symptom Assessment Form [MFSAF] or myeloproliferative neoplasm SAF) from the start of treatment with JAK-inhibitor
4. a score of at least 15 on TSS assessed using the MFSAF v4.0 during screening.
* (ii) Treatment with JAK-inhibitor treatment for>= 3 months duration with maximal doses (e.g., 20-25 mg twice daily ruxolitinib) for that participant and no decrease in spleen volume/size or symptoms as defined in inclusion criterion (i [a, b, or c]).
* (iii) Following maximum tolerated doses of JAK inhibitor therapy for =3 months duration, having documented relapsed disease defined as either

1. Increase in spleen volume from time of best response by 25% measured by MRI or CT, or
2. Increase in spleen size by palpation, CT, or ultrasound

* (b.i) For splenomegaly of 5-10 cm at the start of JAK inhibitor treatment, at least 100% increase in palpable spleen size from time of best response;
* (b.ii) For splenomegaly of > 10 cm at the start of JAK inhibitor treatment, at least 50% increase in palpable spleen size from time of best response;

AND not a candidate for further JAK inhibitor at screening per investigator.

* Measurable splenomegaly demonstrated by a palpable spleen measuring >= 5 cm below the left costal margin or a spleen volume >= 450 cm^3 by MRI or CT
* Active symptoms of MF on the MFSAF v4.0 demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale)
* Hematology laboratory test values within the protocol defined limits
* Biochemical laboratory test values must be within protocol defined limits
* Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
* Participants should follow protocol defined contraceptives procedures
* A woman of childbearing potential must have a negative serum or urine pregnancy test at screening
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Peripheral blood blast count of >= 10% or bone marrow blast count of >=10%
* Known allergies, hypersensitivity, or intolerance to imetelstat or its excipients
* Prior treatment with imetelstat
* Any chemotherapy or MF directed therapy, including investigational drug regardless of class or mechanism of action, immunomodulatory or immunosuppressive therapy, corticosteroids greater than 30 mg/day prednisone or equivalent, and JAK-inhibitor treatment less than equal to 14 days prior to randomization
* Diagnosis or treatment for malignancy other than MF except:

* Malignancy treated with curative intent and with no known active disease present for >= 3 years before randomization
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
* Adequately treated cervical carcinoma in situ without evidence of disease
* Known history of human immunodeficiency virus or any uncontrolled active systemic infection requiring IV antibiotics
* Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus are permitted to enter the study), or any known acute or chronic liver disease requiring treatment unless related to underlying hepatosplenomegaly due to MF
* Major surgery within 28 days prior to randomization
* Any life-threatening illness (e.g., coronavirus disease-2019), medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the participant's safety, interfere with the imetelstat metabolism, or put the study outcomes at undue risk

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
25/11/2026
Actual
Sample size
Target
320
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [4] 0 0
Epworth Healthcare - Richmond
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
4011 - Herston
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
3121 - Richmond
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
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Connecticut
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Indiana
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Taichung City
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Taiwan
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Taipei
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Turkey
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Içel
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Adapazari
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Ankara
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Istanbul
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Izmir
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Turkey
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Yenisehir/Mersin
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United Kingdom
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Kent
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United Kingdom
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London
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United Kingdom
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Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Geron Corporation
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Faye Feller
Address 0 0
Geron Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Michelle Mudge-Riley, DO
Address 0 0
Country 0 0
Phone 0 0
+1 (650) 473-7793
Fax 0 0
Email 0 0
myf3001-info@Geron.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04576156