| CTRI Number |
CTRI/2021/11/037822 [Registered on: 03/11/2021] Trial Registered Prospectively |
| Last Modified On: |
02/04/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
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 of Study
Modification(s)
|
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 |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| 2020-003288-24 |
EudraCT |
| GRN163LMYF3001 Amendment 3 / IND-3 dated 19-Sep-2024 |
Protocol Number |
| NCT04576156 |
ClinicalTrials.gov |
|
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
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| Designation |
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| Affiliation |
|
| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Annappa Kamath |
| Designation |
Executive Director Project Leadership |
| Affiliation |
PAREXEL International Clinical Research Private Limited |
| Address |
CoWrks, Coworking Spaces Pvt. Ltd. – RMZ Eco World, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village, BENGALURU – 560103, Karnataka, INDIA
Bangalore
KARNATAKA
560103
India |
| Phone |
919902096914 |
| Fax |
918067723001 |
| Email |
Annappa.Kamath@PAREXEL.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Dr Annappa Kamath |
| Designation |
Executive Director Project Leadership |
| Affiliation |
PAREXEL International Clinical Research Private Limited |
| Address |
CoWrks, Coworking Spaces Pvt. Ltd. – RMZ Eco World, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village, BENGALURU – 560103, Karnataka, INDIA
Bangalore
KARNATAKA
560103
India |
| Phone |
919902096914 |
| Fax |
918067723001 |
| Email |
Annappa.Kamath@PAREXEL.com |
|
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Source of Monetary or Material Support
|
| Geron Corporation
919 E. Hillsdale Blvd., Suite 250
Foster City, CA 94404
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Primary Sponsor
|
| Name |
Geron Corporation |
| Address |
919 E. Hillsdale Blvd., Suite 250
Foster City, CA 94404
|
| Type of Sponsor |
Pharmaceutical industry-Global |
|
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Details of Secondary Sponsor
|
| Name |
Address |
| PAREXEL International Clinical Research Private Limited |
CoWrks, Coworking Spaces Pvt. Ltd. – RMZ Eco
World, Ground Floor, Bay Area – Adjacent to
Building 6A, Outer Ring Road,
Devarabeesanahalli Village, BENGALURU –
560103, Karnataka, INDIA |
|
|
Countries of Recruitment
|
Belgium
Brazil
Argentina
Australia
Austria
Bulgaria
Colombia
Denmark
France
Georgia
Germany
Hungary
India
Israel
Italy
Malaysia
Poland
Portugal
Republic of Korea
Russian Federation
Singapore
Spain
Switzerland
Taiwan
Turkey
United Kingdom
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 11 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Ashutosh Panigrahi |
All India Institute of Medical Sciences |
Department of Oncology/Hematology, Sijua, Patrapada,
Bhubaneswar 751019
Khordha
ORISSA |
919437147517
06742476731
dr.ashupanigrahi@gmail.com |
| Dr Manoranjan Mahapatra |
All India Institute of Medical Sciences |
Department of
Hematology, Ansari Nagar, 110029
New Delhi
DELHI |
01126594670
911126588663
mrmahapatra@hotmail.com |
| Dr Niti Raizada |
Fortis Hospital Ltd |
Department of Medical and Haemato oncology, 154/9, Bannerghatta
Road, opp to IIM-B 560076
Bangalore
KARNATAKA |
8066214034
08066214444
nitiraizada@icloud.com |
| Dr Meet P Kumar |
Fortis Memorial Research institute |
Clinical Research Department, 2nd Floor, Sector 44, Opposite Huda City Centre Metro Staion 122002
Gurgaon
HARYANA |
01244962200
01244962200
themeetkumar@gmail.com |
| Dr Sameer Ramesh Melinkeri |
LMMFs Deenanth Mangeshkar Hospital and Research Center |
Department of Hematology, Erandawane 411004
Pune
MAHARASHTRA |
2049152023
02040151000
docmelinkeri@yahoo.com |
| Dr Sharat Damodar |
Mazumdar Shaw Medical Center |
Department of Hemato Oncology and Adult BMT, 258 A, Bommasandra Industrial Area, Anekal Taluk, Hosur Road, Bengaluru-560099
Bangalore Rural
KARNATAKA |
18003090309
sharat.damodar.dr@narayanahealth.org |
| Dr Tuphan Kanti Dolai |
Nil Ratan Sircar Medical College and Hospital |
Dept. Of Hematology
138, A.J.C Bose Road, 700014
Kolkata
WEST BENGAL |
9874890275
03322653215
tkdolai@hotmail.com |
| Dr Hasmukh kumar Ranachhodbhai Balar |
Nirmal Hospital Pvt Ltd |
Dept of Hematology, Ring Road, Surat
395002
Surat
GUJARAT |
7030022663
02612333999
drhasmukhbalar@gmail.com |
| Dr Shashikant Apte Janardan |
Sahyadri Super Specialty Hospital |
Department of
Heamatology, 30C, Erandwane, karve Road, 411004
Pune
MAHARASHTRA |
9822404983
02067213000
shashikant.apte@gmail.com |
| Dr Nitin Gupta |
Sir Ganga Ram Hospital, Department of Clinical Hematology |
Department of Clinical Hematology, Sir Ganga Ram Hospital Marg,
Rajinder Nagar,110060
New Delhi
DELHI |
01142251412
01142251412
docnitingupta@gmail.com |
| Dr Ross Cecil Reuben |
St. Johns Medical College and Hospital |
Department of
Medicine and
Haematology, Sarjapur Road, 560034
Bangalore
KARNATAKA |
8022065229
08022065008
cecilrross@gmail.com |
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Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 11 |
| Name of Committee |
Approval Status |
| Fortis Hospital Ethics Committee |
Approved |
| Institutional Ethics Committee St. Johns Medical College |
Approved |
| Institutional Ethics Committee, AIIMS Hospital, New Delhi |
Approved |
| Institutional Ethics Committee, All India Institute of Medical Sciences |
Approved |
| Institutional Ethics Committee, Fortis Memorial Research Institute |
Approved |
| Institutional Ethics Committee, Lata Mangeshkar Medical Foundation’s, Deenanath Mangeshkar Hospital and Research Centre |
Approved |
| Narayana Health Medical Ethics Committee |
Approved |
| Nirmal Hospital Pvt. ltd. Ethics Committee |
Approved |
| NRS Ethics Committee, Office of the Principal, NRS Medical College and Hospital |
Approved |
| Sahyadri Hospitals Limited Ethics Committee |
Approved |
| Sir Ganga Ram Hospital Ethics Committee |
Approved |
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Regulatory Clearance Status from DCGI
Modification(s)
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D474||Osteomyelofibrosis, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
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, and chemotherapy |
| Intervention |
Imetelstat |
Imetelstat will be given intravenously at 9.4 mg/kg every 21 days, until disease progression or unacceptable toxicity, treatment discontinuation or study end.
Other Name: GRN163L
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Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
• 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) or (ii):
(i) Treatment with JAK-inhibitor for greater than or equal to 6 months duration, including at least 2 months at an optimal dose as assessed by the investigator for that participant and 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 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 greater than or equal to 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
-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
- For splenomegaly of greater than 10 cm at the start of JAK inhibitor treatment, at least 50% increase in palpable spleen size from time of best response
• Measurable splenomegaly demonstrated by a palpable spleen measuring greater than or equal to 5 cm below the left costal margin or a spleen volume greater than or equal to 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
|
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| ExclusionCriteria |
| Details |
• Peripheral blood blast count of greater than or equal to 10% or bone marrow blast count of greater than or equal to 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
1. Malignancy treated with curative intent and with no known active disease present for greater than or equal to 3 years before randomization
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
3. 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 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 investigators opinion, could compromise the participants safety, interfere with the imetelstat metabolism, or put the study outcomes at undue risk
|
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Method of Generating Random Sequence
|
Stratified randomization |
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Method of Concealment
|
Centralized |
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Blinding/Masking
|
Open Label |
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Primary Outcome
|
| Outcome |
TimePoints |
| Overall survival |
Baseline (Day 1) until End of Study (EOS) (approximately 3 years) |
|
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Secondary Outcome
|
| Outcome |
TimePoints |
| Symptom response rate |
Baseline (Day 1), and at Week 24 |
| Progression-free survival |
Baseline (Day 1) until End of Study (EOS) (approximately 3 years) |
| Spleen response rate |
Baseline (Day 1), and at Week 24 |
| Complete remission (CR), partial remission (PR), clinical improvement (CI), spleen response, symptoms response, and anemia response per modified 2013 IWG-MRT criteria |
Baseline (Day 1) until End of Treatment (approximately 3 years) |
| Reduction in the degree of bone marrow fibrosis |
Baseline (Day 1) until End of Treatment (approximately 3 years) |
| Number of Participants with Adverse Events |
Screening (Day -28 to -1) until End of Study (approximately 3 years) |
| Assessment of Cmax |
Day 1 of all cycles (each cycle is 21 days) |
| European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30) scores |
Baseline to End of Study (approximately 3 years) |
| EuroQol-EQ-5D (EQ-5D-5L) questionnaire scores |
Baseline to End of Study (approximately 3 years) |
| Assessment of AUC |
Day 1 of all cycles (each cycle is 21 days) |
|
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Target Sample Size
|
Total Sample Size="320"
Sample Size from India="34"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
31/12/2021 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
12/04/2021 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
• Gabriela M. Baerlocher, M.D., Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia, n engl j med 373;10
• Ayalew Tefferi, M.D., A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis, n engl j med 373;10
• Tefferi A, Imetelstat therapy in refractory anemia with ring sideroblasts with or without thrombocytosis, Blood cancer Journal (2016) 6, e405
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
Modification(s)
|
The purpose of the study is to evaluate the overall survival of participants treated with imetelstat compared to best available therapy with intermediate-2 or high-risk Myelofibrosis (MF) who are relapsed/refractory to Janus Kinase (JAK)-Inhibitor treatment |