Study to Evaluate Imetelstat (GRN163L) in Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS).

• Register: EUCTR
• Last refreshed on: 8 November 2021
• Main ID: EUCTR2015-002874-19-DE
• Date of registration: 06/10/2015
• Prospective Registration: Yes
• Primary sponsor: Geron Corporation
• Public title: Study to Evaluate Imetelstat (GRN163L) in Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS).
• Scientific title: A Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) that is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
• Date of first enrolment: 25/04/2016
• Target sample size: 170
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002874-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Czech Republic, Czechia, France, Germany, Israel, Italy, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trial Enquiries
• Affiliation: Geron Corporation

• Name: Clinical Trial Enquiries
• Affiliation: Geron Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
1. Man or woman =18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place);
2. Criterion modified per Amendment 1.
2.1. Criterion modified per Amendment 2.
2.2. Criterion modified per Amendment 3.
2.3 In part 1, diagnosis of MDS according to WHO criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to C1D1. A local laboratory report from this diagnostic bone marrow aspirate and biopsy must be reviewed and approved by the sponsor (Attachment 1). In Part 2, diagnosis of MDS according to WHO criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to Study Entry (Attachment 1). A sample of the baseline bone marrow aspirate and biopsy must be submitted to the Independent Central Pathology Reviewer for diagnostic confirmation. Central laboratory review is required to confirm diagnosis prior to randomization.
3. IPSS low Risk or intermediate-1 risk MDS (Attachment 3);
4. Criterion modified per Amendment 1.
4.1. RBC transfusion dependent, defined as requiring at least 4 RBC units transfused over
an 8-week period during the 16 weeks prior to C1D1 (Part 1) or Randomization (Part 2)(defined in Section 3.1); pre-transfusion Hb should be =9.0 g/dL to count towards the 4 units total;
5. Has MDS that is relapsed/refractory to ESA treatment; as defined by meeting any one of the
criteria below:
5.1. Received at least 8 weeks of treatment with a minimum weekly dose of epoetin alfa
40,000 U, epoetin beta 30,000 U or darbepoetin alfa 150 mcg (or equivalent agent/dose), without having achieved a Hb rise =1.5 g/dL or decreased RBC transfusion requirement by at least 4 units over 8 weeks
5.2.1 Transfusion dependence or reduction in Hb by =1.5 g/dL after hematologic improvement from at least 8 weeks of treatment with therapies outlined in inclusion criteria 5.1, in the absence of another explanation.
5.4. Endogenous serum EPO level >500 mU/mL;
...
More details see protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion criteria:
1. Subject has known allergies, hypersensitivity, or intolerance to imetelstat or its excipients (refer to the IB 25)
2. Subject has received an experimental or investigational drug or used an invasive investigational medical device within 30 days prior to C1D1 (Part 1) or Randomization (Part 2) (defined in Section 3.1) or is currently enrolled in an investigational study;
3.Prior treatment with imetelstat;
4. Criterion modified per Amendment 2
4.1 Have received corticosteroids > 30 mg/day prednisone or equivalent, or growth factor treatment within 4 weeks prior to C1D1 (Part 1) or Randomization (Part 2)
5. Criterion modified per Amendment 2.
5.2 Criterion 5.2 replaced by criterion 5.2.1 per Amendment 5.
5.2.1 Prior treatment with lenalidomide, thalidomide, or other thalidomide analogues;
5.3 Criterion 5.3 replaced by criterion 5.3.1 per Amendment 5.
5.3.1 Has received an ESA or any anti-MDS therapy, chemotherapy, immunomodulatory, or immunosuppressive therapy within 4 weeks prior to C1D1 (Part 1) or Randomization (Part 2) (8 weeks for long-acting ESAs);
6. Prior history of hematopoietic stem cell transplant;
7. Anemia attributed to factors other than MDS (including hemolysis, chronic renal failure, hepatitis, gastrointestinal bleeding);
8. Major surgery within 4 weeks prior to C1D1 (Part 1) or Randomization (Part 2)(excluding the placement of vascular access and other minor surgical procedures);
9. Diagnosed or treated for malignancy other than MDS, except:
9.1. Malignancy treated with curative intent and with no known active disease present for =3 years before C1D1 (Part 1) or Randomization (Part 2)
9.2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
9.3. Adequately treated cervical carcinoma in situ without evidence of disease;
10. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of C1D1 (Part 1) or Randomization (Part 2), or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification;
...
More details see protocol



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Myelodysplastic syndrome (MDS)
MedDRA version: 20.0 Level: HLT Classification code 10028536 Term: Myelodysplastic syndromes System Organ Class: 100000004851

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Imetelstat sodium
Product Code: GRN163L
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: Imetelstat sodium
CAS Number: 1007380-31-5
Current Sponsor code: GRN163L
Other descriptive name: IMETELSTAT SODIUM
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 210-
Pharmaceutical form of the placebo: Lyophilisate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Percentage of participants without any red blood cell (RBC) transfusion during any consecutive 8 week period.

Secondary Objective: - To assess the safety of imetelstat in subjects with MDS
- To assess the time to RBC TI and duration of RBC TI
- To assess the rate of hematologic improvement
- To assess the rates of CR, PR or marrow complete remission (mCR)
- To assess OS
- To assess progression free survival (PFS)
- To assess time to progression to AML
- To assess the rate and amount of supportive care, including transfusions and myeloid growth factors (Part 2 only)
- To evaluate the pharmacokinetics and immunogenicity of imetelstat in subjects with MDS
- To assess the effect of imetelstat treatment on patient reported outcomes (PROs)
- To assess the effect of treatment on medical resource utilization (Part 2 only)
- To assess the effect of imetelstat on corrected QT (QTc) interval in
subjects in the Ventricular Repolarization substudy (to be reported
separately from Part 2)

Timepoint(s) of evaluation of this end point: 8 weeks

Main Objective: Part 1: To evaluate the efficacy and safety of imetelstat in transfusion dependent subjects with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment.

Part 2: To compare the efficacy, in terms of RBC TI, of imetelstat to placebo in transfusion dependent subjects with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1/ up to follow-up (30 days posttreatment [approximately 2 years])
2-5/ up to 2 years after enrollment of the last participant

Secondary end point(s): 1. - Safety profiles of imetelstat in subjects with MDS (eg, incidence, intensity, and type of adverse events, vital signs measurements, clinical laboratory values, ECGs, and deaths);
2. - 24-week RBC TI rate, defined as the proportion of subjects without any RBC transfusion during any consecutive 24 weeks (168 days) starting from Study Day 1;
3. - Time to the 8-week RBC TI, defined as the interval from Study Day 1 to the first day of the first 8-week RBC TI period;
4. - Duration of RBC TI, defined as the first day of the first 8-week RBC TI period to the date of the first RBC transfusion after the TI period;
5. - Rate of hematologic improvement, including HI-E, per IWG 2006;
6. OS, defined as the interval from Study Day 1 to death from any cause.
Survival time of living subjects will be censored on the last date a subject is known to be alive or lost to follow-up;
7. Progression free survival, defined as the time interval from Study Day 1 to the first date of disease progression or death from any cause, whichever occurs first. For subjects who do not have documented disease progression and who are still alive at the end of the study or clinical cutoff will be censored at the last disease evaluation date.
8. Time to progression to AML, defined as the interval from Study Day 1 to the date of AML diagnosis. For subjects who have not progressed to AML and are still alive at the cutoff date for the analysis or who withdraw from the study (withdrawal of consent or lost to follow-up), data will be censored at the date of the last disease evaluation;
9. Amount and relative change in RBC transfusions;
10. Rate of myeloid growth factors usage, defined as the proportion of subjects receive any myeloid growth factors starting from Study Day 1; duration of myeloid growth factor administered starting from Study Day 1;
11. Assessment of QUALMS, FACT-An, and EQ-5D-5L;
12. Pharmacokinetic parameters (eg, Cmax, AUC0-t), and immunogenicity of imetelstat (eg, antibodies to imetelstat);
13. Medical resource utilization data including hospitalization,
emergency room visits, and hematology specialist visits;
14. ECG parameters including change in QT interval by Fridericia's
correction method (?QTcF) in the Ventricular Repolarization substudy
(Part 2 only).

Secondary ID(s)

2015-002874-19-FR

63935937MDS3001

Source(s) of Monetary Support

Geron Corporation

Ethics review

Status: Approved
Approval date: 25/04/2016
Contact: