A Randomized Trial Testing Early Versus Late Onset of Epo Alfa Treatment in Lower Risk MDS with Non Rbc Transfusion Dependent Anemia and without Del 5Q

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe Francophone Des Myelodysplasies

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

17 Apr 2018 → 29 Oct 2024

Decision date (initial)

2024-09-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

JANSSEN

External identifiers

EU CT number

2024-515356-21-00

EudraCT number

2017-000812-41

ClinicalTrials.gov

NCT03223961

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

Randomly compare, in non RBC transfusion dependent lower risk MDS with anemia, the time to RBC transfusion dependence in patients with early onset of EPO ALFA (at inclusion) and patients with delayed onset of EPO ALFA (at the threshold chosen for RBC transfusions)

Secondary objectives 7

1. Compare in those 2 randomized groups erythroid response (according to IWG 2006 criteria) after 12 weeks of EPO ALFA treatment
2. Compare in those 2 randomized groups, response duration to EPO ALFA
3. Compare in those 2 randomized groups, progression to higher risk MDS and /or AML
4. Compare in those 2 randomized groups, the incidence of cardiovascular events
5. Compare in those 2 randomized groups, QoL (assessed based on usual scales)
6. Compare in those 2 randomized groups, Overall survival
7. We will also analyse biological correlates and compare in those 2 groups the ex vivo effect of EPO ALFA on erythropoiesis, in particular on the disease clonal architecture by repeated next generation sequencing (NGS) analysis of somatic mutations. One hypothesis is that by beginning EPO ALFA early in the disease course, no or less mutated erythropoiesis may be amplified by EPO ALFA at the expense of more mutated clones, thereby potentially delaying the disease course.

Conditions and MedDRA coding

Adult subject (18 years of age older) with low or intermediate-1 IPSS risk MDS with transfusions independent anemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥ 18 years at the time of signing the informed consent form
2. Must understand and voluntarily sign the informed consent form
3. Diagnosis of MDS according to WHO 2016 criteria, and low or int 1 classical IPSS, including CMML with WBC <13G/l
4. No 5q deletion
5. Non-RBC transfusion dependent anemia with Hb level between 9.0 and 10.5 g/dl at the center's lab, and at least 1g/dl higher than the Hb threshold chosen to start RBC transfusions for the patient based on age, comorbidities and anticipated clinical tolerance of anemia (this transfusion threshold is generally set at 8g/dl but can be increased up to 9g/dl in case of comorbidity, etc…(as an example, a patient with a transfusion threshold estimated to be 8.5g/dl can be entered only if the baseline Hb level is at least 9.5 g/dl)
6. Serum EPO level <500U/l, no other cause of anemia (iron deficiency, vitamin B12 or B9 deficiency, hemolysis, hypothyroidism…)
7. Performance status ≤ 2

Exclusion criteria 11

1. Higher risk MDS (IPSS intermediate-2 or high)
2. Del 5q
3. Baseline Hemoglobin level > 10.5 g/dl or < 9 g/dl
4. Transfusion threshold (based on age, comorbidities…) > 9 g/dl
5. Transfusion threshold less than 1 g/dl below baseline Hb level
6. RBC transfusion dependence. Patients may have received only one transfusion series for adverse event or surgery prior to inclusion.
7. CMML, if > 10 % BM blasts or WBC > 13.000/mm3
8. Uncontrolled hypertension
9. Uncontrolled cardiovascular disease including angina pectoris or cardiac failure
10. Renal failure: Creatinine clearance < 40 ml/min (using MDRD formula)
11. Pregnancy (positive βHCG) or nursing

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Comparison of the time to RBC transfusion dependence between patients with early onset of EPO ALFA (at inclusion) and patients with delayed onset of EPO ALFA (at the threshold chosen for RBC transfusion)

Secondary endpoints 4

1. IWG 2006 erythroid response and duration
2. QoL
3. OS
4. Molecular biology corrélations

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Francophone Des Myelodysplasies

Sponsor organisation

Groupe Francophone Des Myelodysplasies

Address

Opital St Louis Hemato Seniors T4, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris

Postcode

75010

Country

France

Scientific contact point

Organisation

Groupe Francophone Des Myelodysplasies

Contact name

Sophie PARK

Public contact point

Organisation

Groupe Francophone Des Myelodysplasies

Contact name

Sophie PARK

Locations

1 EU/EEA country · 41 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 10 files

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

Application history

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