A study comparing current available therapies with imetelstat for the treatment of intermediate-2 or high-risk MF who are not responding to JAK-inhibitor treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Geron Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Apr 2021 → ongoing

Decision date (initial)

2024-03-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-509120-17-00

EudraCT number

2020-003288-24

ClinicalTrials.gov

NCT04576156

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Pharmacokinetic, Efficacy, Others

The primary objective of this study is to compare the overall survival (OS) of participants, treated with imetelstat versus BAT, with intermediate-2 or high-risk Myelofibrosis (MF) whose disease is relapsed / refractory to JAK-inhibitor treatment.

Secondary objectives 1

1. To evaluate imetelstat versus BAT with respect to: - Symptom response rate at Week 24, defined as the proportion of participants who have ≥ 50% reduction in total symptom score (TSS) at Week 24 from baseline as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 e-diary questionnaire - Progression-free survival, defined as the time interval from randomization date to the first date of disease progression or death from any cause, whichever occurs first - Spleen response rate at Week 24, defined as the proportion of participants who achieve ≥ 35% spleen volume reduction (SVR) at Week 24 from baseline as measured by magnetic resonance imaging (MRI) or computed tomography scan and assessed by Central Radiology Review. Additionally, SVR of ≥ 20% and ≥ 10% at Week 24 will be assessed. - Complete remission, partial remission, clinical improvement, spleen response, symptoms response, and anemia response per modified 2013 IWG MRT criteria

Conditions and MedDRA coding

Myelofibrosis

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Diagnosis of PMF according to the revised WHO criteria (Section 18.2); or PET-MF or PPV-MF according to the IWG-MRT criteria (Section 18.3) confirmed by local pathology report.
2. Dynamic International Prognostic Scoring System intermediate-2 or high-risk MF (Section 18.4).
3. Relapsed / Refractory to JAK-inhibitor treatment as defined in either inclusion 4.1, 4.2 or 4.3 and not eligible for ASCT at screening: 4.1: 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: a) no decrease in spleen volume (< 10% by MRI or CT) from the start of treatment with JAK-inhibitor. b) no decrease in spleen size (< 30% by palpation or length by imaging) from start of treatment with JAK-inhibitor. c) no decrease in symptoms (< 20% by MFSAF or myeloproliferative neoplasm SAF) from start of treatment with JAK-inhibitor. d) a score of at least 15 on TSS assessed using the MFSAF v4.0 (adapted as the MF Symptom Recall Form, Section 18.6) during screening. 4.2: Treatment with JAK-inhibitor for ≥ 3 months duration with maximal doses for that participant (e.g. 20-25 mg twice daily ruxolitinib) without a spleen or symptom response as defined in inclusion criterion 4.1 (a, b, or c) and would not benefit from remaining on treatment for 6 months. 4.3: Following maximum tolerated doses of JAK inhibitor therapy for ≥3 months duration, having documented relapsed disease defined as either: • Increase in spleen volume from time of best response by 25% measured by MRI or CT, or • 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 > 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.
4. Measurable splenomegaly demonstrated by a palpable spleen measuring ≥ 5 cm below the left costal margin or a spleen volume ≥ 450 cm3 by MRI or CT.
5. Active symptoms of MF on the MFSAF v4.0 (adapted as the MF Symptom Recall Form, Section 18.6) demonstrated by a symptom score of at least 5 points (on a 0 to 10 scale) on at least 1 of the symptoms or a score of 3 or greater on at least 2 of the following symptoms: fatigue, night sweats, itchiness, abdominal discomfort, pain under ribs on left side, early satiety, and bone pain.
6. Hematology laboratory test values within the following limits: • absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L independent of growth factor support, AND • platelets ≥ 75 x 10^9/L independent of platelet transfusion support.

Exclusion criteria 6

1. Peripheral blood blast count of ≥ 10% or bone marrow blast count of ≥ 10%.
2. Prior treatment with imetelstat.
3. Any chemotherapy or MF directed therapy, including investigational drug regardless of class or mechanism of action, immunomodulatory or immunosuppressive therapy, corticosteroids > 30 mg/day prednisone or equivalent, and JAK-inhibitor treatment ≤ 14 days prior to randomization.
4. 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.
5. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
6. Known history of human immunodeficiency virus or any uncontrolled active systemic infection requiring IV antibiotics.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS), defined as the time interval from randomization date to date of death from any cause.

Secondary endpoints 3

1. Symptom response rate at Week 24 (defined as the proportion of patients who have ≥ 50% reduction in TSS at Week 24 from baseline as measured by the MFSAF v4.0)
2. Progression-Free Survival, defined as the time interval from randomization date to the first date of disease progression (worsening splenomegaly or leukemic transformation per 2013 IWG-MRT criteria) or death from any cause, whichever occurs first.
3. Spleen response rate at Week 24 (defined as the proportion of patients who achieve ≥ 35% reduction in spleen volume at Week 24 from baseline as measured by imaging scans). For additional secondary end points please refer to the study protocol.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Geron Corp.

Sponsor organisation

Geron Corp.

Address

919 East Hillsdale Boulevard Suite 250

City

Foster City

Postcode

94404-3296

Country

United States

Scientific contact point

Organisation

Geron Corp.

Contact name

Clinical Trial Enquiries

Public contact point

Organisation

Geron Corp.

Contact name

Clinical Trial Enquiries

Third parties 14

Locations

11 EU/EEA countries · 83 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 96 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications