Luspatercept Plus CsA vs CsA for the Treatment of Newly Diagnosed Non-Transfusion-Dependent NSAA

NCT06424639 | Not Yet Recruiting Phase 4

• 1 other identifier: LC-001
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

In a randomized, controlled clinical trial, the efficacy and safety of rodsipil combined with cyclosporine versus cyclosporine alone in the treatment of newly diagnosed non-transfusion-dependent NSAA were compared.

Conditions

Aplastic Anemia

Keywords

Aplastic Anemia; Luspatercept; CsA; randomized controlled study

Outcome Measures

Primary Outcomes (1)

• overall response rate (ORR)

  Proportion of patients who achieved complete response, partial response and hematological response

  6 month

Secondary Outcomes (2)

• overall response rate (ORR)

  12 month

• adverse event rate

  12 month

Study Arms (2)

Luspatercept combined with cyclosporine

EXPERIMENTAL

Administered Luspatercept (1.0 mg/kg, subcutaneous injection every 3 weeks), and Cyclosporine (3-5mg/kg/day) adjusted according to hematological parameters, for at least 6 months to evaluate efficacy. Effective patients will continue to receive Cyclosporine treatment for at least 1.5 years, followed by a gradual reduction in dosage.

Drug: Luspatercept; Drug: cyclosporine

cyclosporine

EXPERIMENTAL

Give cyclosporine 3-5mg/kg/day, adjust the dose based on the blood count, and administer it for at least 6 months to evaluate the efficacy. If effective, the patient will continue to receive cyclosporine treatment for at least 1.5 years, followed by a gradual reduction in dosage.

Drug: cyclosporine

Interventions

Luspatercept DRUG

Luspatercept (dose of 1.0 mg/kg, subcutaneous injection every 3 weeks) Cyclosporine (3-5mg/kg/day)

Also known as: cyclosporine

Luspatercept combined with cyclosporine

cyclosporine DRUG

Cyclosporine (3-5mg/kg/day)

Luspatercept combined with cyclosporine; cyclosporine

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Hemoglobin level of 6-10 g/dL
• Definition of NSAA: Patients with AA diagnosis but not SAA or VSAA diagnosis (at least two of the following conditions can be diagnosed as AA: (i) Hemoglobin \< 100 g/L; (ii) Platelet count \< 50×10\^9/L; (iii) Neutrophil count \< 1.5×10\^9/L. SAA diagnosis criteria include less than 25% (or 25-50%, but residual hematopoietic cells \< 30%) of bone marrow cells, plus at least two of the following conditions: (i) Neutrophil count \< 0.5×10\^9/L; (ii) Platelet count \< 20×10\^9/L; (iii) Retroperitoneal lymph node count \< 20×10\^9/L. VSAA meets the criteria for SAA, but with neutrophil count \< 0.2×10\^9/L. (British guidelines, 2015))
• No active infection
• No other concurrent neoplasms (except in situ carcinoma)
• Baseline liver and renal function within 1.5 times of normal value
• No pregnancy or breastfeeding
• Agree to sign informed consent form
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

You may not qualify if:

• Congenital aplastic anemia
• Presence of chromosomal aberrations
• Cytogenetic evidence of clonal hematological myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML)
• PNH clone ≥50%
• Previous use of alemtuzumab, any ATG, or any dose of cyclosporine for immunosuppressive treatment
• Previous hematopoietic stem cell transplant (HSCT)
• Uncontrolled infection or bleeding under standard treatment
• Allergy to rituximab, cyclosporine, or excipients
• History of allergy to polyethylene glycol (PEG) 80
• Active infection or cirrhosis of the liver or portal hypertension due to HIV, HCV, or HBV
• Screening QTcF (Fridericia QT corrected formula) less than 450 milliseconds or less than 480 milliseconds of bundle branch block determined by three ECG averages, and assessed on-site; unstable angina; uncontrolled hypertension (\>180/100 mmHg); pulmonary hypertension
• Any malignant tumor within 5 years, except local basal cell carcinoma; previous thromboembolic event, history of myocardial infarction or stroke (including antiphospholipid syndrome); currently using anticoagulants
• Pregnant or lactating women
• Participated in another clinical trial within 3 months

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Related Publications (14)

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  PMID: 7616805 BACKGROUND

• Young NS. Aplastic Anemia. N Engl J Med. 2018 Oct 25;379(17):1643-1656. doi: 10.1056/NEJMra1413485. No abstract available.

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• Bacigalupo A. How I treat acquired aplastic anemia. Blood. 2017 Mar 16;129(11):1428-1436. doi: 10.1182/blood-2016-08-693481. Epub 2017 Jan 17.

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• Yang C, Zhang X. Incidence survey of aplastic anemia in China. Chin Med Sci J. 1991 Dec;6(4):203-7.

  PMID: 1813058 BACKGROUND

• Vaht K, Goransson M, Carlson K, Isaksson C, Lenhoff S, Sandstedt A, Uggla B, Winiarski J, Ljungman P, Brune M, Andersson PO. Incidence and outcome of acquired aplastic anemia: real-world data from patients diagnosed in Sweden from 2000-2011. Haematologica. 2017 Oct;102(10):1683-1690. doi: 10.3324/haematol.2017.169862. Epub 2017 Jul 27.

  PMID: 28751565 BACKGROUND

• Li H, Fu L, Yang B, Chen H, Ma J, Wu R. Cyclosporine Monotherapy in Pediatric Patients With Non-severe Aplastic Anemia: A Retrospective Analysis. Front Med (Lausanne). 2022 Mar 7;9:805197. doi: 10.3389/fmed.2022.805197. eCollection 2022.

  PMID: 35342744 BACKGROUND

• Kubasch AS, Fenaux P, Platzbecker U. Development of luspatercept to treat ineffective erythropoiesis. Blood Adv. 2021 Mar 9;5(5):1565-1575. doi: 10.1182/bloodadvances.2020002177.

  PMID: 33687432 BACKGROUND

• Attie KM, Allison MJ, McClure T, Boyd IE, Wilson DM, Pearsall AE, Sherman ML. A phase 1 study of ACE-536, a regulator of erythroid differentiation, in healthy volunteers. Am J Hematol. 2014 Jul;89(7):766-70. doi: 10.1002/ajh.23732. Epub 2014 Apr 26.

  PMID: 24715706 BACKGROUND

• Suragani RN, Cadena SM, Cawley SM, Sako D, Mitchell D, Li R, Davies MV, Alexander MJ, Devine M, Loveday KS, Underwood KW, Grinberg AV, Quisel JD, Chopra R, Pearsall RS, Seehra J, Kumar R. Transforming growth factor-beta superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med. 2014 Apr;20(4):408-14. doi: 10.1038/nm.3512. Epub 2014 Mar 23.

  PMID: 24658078 BACKGROUND

• Markham A. Luspatercept: First Approval. Drugs. 2020 Jan;80(1):85-90. doi: 10.1007/s40265-019-01251-5.

  PMID: 31939073 BACKGROUND

• Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Diez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Gotze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellstrom-Lindberg E, Zeidan AM, Ades L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. N Engl J Med. 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892.

  PMID: 31914241 BACKGROUND

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  PMID: 35220402 BACKGROUND

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  PMID: 12648074 BACKGROUND

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

luspatercept; Cyclosporine

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Bing Bing, PhD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bing Bing, PhD

CONTACT

13601059938; Hanbing_li@sina.com.cn

QLin Hu, PhD

CONTACT

15810785167; HQLin2012@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: May 22, 2024
• Study Start: May 1, 2024
• Primary Completion: May 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 22, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)