Efficacy and Safety of Luspatercept for the Treatment of Anemia Due to Myelodysplastic Syndromes with del5q refractory/resistant/intolerant to Prior Treatments, Who Require Red Blood Cell Transfusion.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Associazione Qol-One

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

27 Jan 2025 → ongoing

Decision date (initial)

2025-01-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-519310-31-00

EudraCT number

2021-001538-20

ClinicalTrials.gov

NCT05924100

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Others

Primary objective:
• to evaluate the effect of luspatercept on RBC TI (lack of transfusions for 8 consecutive weeks within the first 24 weeks) in subjects with MDS with del5q with IPSS-R very low, low, or intermediate risk and < 5% bone marrow blasts, resistant/refractory/intolerant to lenalidomide and RBC TD.

Secondary objectives 1

1. secondary objectives: • to evaluate o the safety and tolerability of luspatercept o RBC-TI at 48 weeks and end of study o the duration of RBC-TI o the reduction in RBC transfusions o the increase in hemoglobin o the change in quality of life scores (ie, QOL-E and HM-PRO) o the change in serum ferritin o the change in iron chelation therapy use o the time to RBC TI

Conditions and MedDRA coding

Anemia due to MDS with del5q with IPSS-R very low, low, or intermediate risk MDS and abone marrow blast count of < 5% , Refractory or intolerant to, or ineligible for, prior ESA treatment and for prior lenalidomide treatment and who require RBC transfusions.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Subject is ≥ 18 years of age the time of signing the informed consent form (ICF).
2. 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
3. 3. Documented diagnosis of MDS with del5q according to 2018 WHO classification.
4. 4. IPSS-R classification (Greenberg, 2012) of very low, low, or intermediate risk disease, and: • < 5% blasts in bone marrow • Peripheral blood WBC count <13,000/μL
5. 5. Refractory or intolerant to, or ineligible for, prior ESA treatment.
6. 6. If previously treated with ESAs or granulocyte colony-stimulating factor (G-CSF), both agents must have been discontinued ≥ 4 weeks prior to date of screening.
7. 7. Refractory or intolerant to, or ineligible for, prior lenalidomide treatment, as defined by any one of the following: • Refractory to prior lenalidomide treatment for at least 4 cycles; - documentation of non-response or response that is no longer maintained (HI-E) • Intolerant to prior lenalidomide treatment - documentation of discontinuation of lenalidomide at any time after introduction due to intolerance or an adverse event • lenalidomide ineligible –platelet counts below 50000/mmc or absolute neutrophil count below 500/mmc at the start of treatment • lenalidomide must have been discontinued ≥ 4 weeks prior to date of screening. Requires RBC transfusions, as documented by the following criteria: • average transfusion requirement of ≥ 2 units/8 weeks of pRBCs confirmed for a minimum of 16 weeks immediately preceding enrolment. • Hb levels at the time of or within 7 days prior to administration of a RBC transfusion must have been ≤ 10.0 g/dL in order for the transfusion to be counted towards meeting eligibility criteria. RBC transfusions administered when Hb levels were > 10.0 g/dL and/or RBC transfusions administered for elective surgery will not qualify as a required transfusion for the purpose of meeting eligibility criteria. • no consecutive 56-day period that was RBC transfusion-free during the 16 weeks immediately preceding screening
8. 8. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2.
9. 9. Females of childbearing potential, defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months), must: • Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy (unless the screening pregnancy test was done within 72 hours of C1D1). Refer to Section 6.1 for additional details. She must agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. • If sexually active, agree to use, and be able to comply with, highly effective contraception without interruption, 5 weeks prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks after discontinuation of study therapy.
10. 10. Male subjects must: • Agree to use a condom, defined as a male latex condom or non latex condom not made out of natural (animal) membrane (for example, polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks following investigational product discontinuation, even if he has undergone a successful vasectomy.
11. 11. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion criteria 12

1. 1. Prior therapy with disease modifying agents for underlying MDS disease (hypomethylating agents) • subjects who previously received HMA may be enrolled at the investigator’s discretion contingent that the subject received no more than 1 dose of HMA). The last dose must be ≥ 5 weeks from the date of screening.
2. 2. Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
3. 3. Secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.
4. 4. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
5. 5. Prior allogeneic or autologous stem cell transplant.
6. 6. Known history of diagnosis of AML
7. 7. Use of any of the following within 5 weeks prior to study entry: • anticancer cytotoxic chemotherapeutic agent or treatment • corticosteroid, except for subjects on a stable or decreasing dose for ≥ 1 week prior to study entry for medical conditions other than MDS • iron-chelating agents, except for subjects on a stable or decreasing dose for at least 8 weeks prior to screening • other RBC hematopoietic growth factors • investigational drug or device, or approved therapy for investigational use. If the half-life of the previous investigational product is known, use within 5 times the half- life prior to screening or within 5 weeks, whichever is longer is excluded
8. 8. Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment
9. 9. Estimated glomerular filtration rate (eGFR) or creatinine clearance < 40 mL/min.
10. 10. Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase or alanine aminotransferase/serum glutamic pyruvic transaminase ≥ 3.0 x upper limit of normal (ULN)
11. 11. Total bilirubin ≥ 2.0 x ULN. • higher levels are acceptable if these can be attributed to active red blood cell precursor destruction within the bone marrow (ie, ineffective erythropoiesis) or in the presence of known history of Gilbert Syndrome. • subjects are excluded if there is evidence of autoimmune hemolytic anemia
12. 12. Prior history of malignancies, other than MDS, unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 5 years. However, subjects with the following history/concurrent conditions are allowed: • Basal or squamous cell carcinoma of the skin • Carcinoma in situ of the cervix • Carcinoma in situ of the breast • Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. RBC Transfusion Independence (for 8 weeks in the first 24 weeks)

Secondary endpoints 9

1. Safety and tolerability of Luspatercept
2. RBC-TI at 48 weeks and end of the study
3. Duration of RBC-TI
4. Reduction in RBC transfusions
5. Increase in hemoglobin
6. Change in quality of life scores (ie. QOL-E and HM-PRO)
7. Change in Serum Ferritin
8. Change in iron chelation therapy use
9. Time to RBC TI

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Associazione Qol-One

Sponsor organisation

Associazione Qol-One

Address

Via Carro E Quattrone 8

City

Reggio Calabria

Postcode

89134

Country

Italy

Scientific contact point

Organisation

Associazione Qol-One

Contact name

Esther Natalie Oliva

Public contact point

Organisation

Associazione Qol-One

Contact name

Roberta Siclari

Locations

1 EU/EEA country · 30 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 7 files

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

Application history

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