## Protocol Section
### Identification Module
**NCT ID:** NCT06424639

**Brief Title:** Luspatercept Plus CsA vs CsA for the Treatment of Newly Diagnosed Non-Transfusion-Dependent NSAA

**Official Title:** A Randomized, Controlled Trial Comparing the Safety and Efficacy of Luspatercept Plus Cyclosporine Versus Cyclosporine Alone for the Treatment of Newly Diagnosed Non-transfusion-dependent Non-severe Aplastic Anemia (NSAA)

#### Organization Study ID Info
**ID:** LC-001
#### Organization
**Class:** OTHER
**Full Name:** Peking Union Medical College Hospital
### Status Module
#### Completion Date
**Date:** 2025-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-05

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-22
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-16
**Study First Submit QC Date:** 2024-05-16
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Peking Union Medical College Hospital

#### Responsible Party

**Investigator Affiliation:** Peking Union Medical College Hospital

**Investigator Full Name:** Bing Han

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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.

**Detailed Description:** Conduct a comparative evaluation of the effectiveness and safety of Luspatercept combined with cyclosporine versus cyclosporine monotherapy in the treatment of newly diagnosed non-transfusion-dependent non-severe aplastic anemia (NSAA). Patients were randomized in a 1:1 ratio and assigned to one of two groups: Group A, Luspatercept combined with cyclosporine: received Luspatercept (1.0 mg/kg, subcutaneous injection every 3 weeks), cyclosporine (3-5mg/kg/day), adjusted based on hematological parameters, for at least 6 months to assess efficacy. Effective patients continued to receive cyclosporine treatment for at least 1.5 years, with a gradual reduction in dosage; Group B, cyclosporine: received 3-5mg/kg/day, adjusted based on hematological parameters, for at least 6 months to assess efficacy, with effective patients continuing to receive cyclosporine treatment for at least 1.5 years, with a gradual reduction in dosage. Hgb below 60g/L was allowed, or in emergency conditions, blood transfusion was allowed. Platelets below 20×10\^9/L or with obvious bleeding tendency were allowed to receive platelet transfusion. If neutrophil count was below 1.0×10\^9/L, G-CSF was allowed until neutrophil count recovered to above 1.0×10\^9/L. Symptoms, treatment-related adverse events, signs, blood transfusion volume, and laboratory tests (including reticulocyte count) were recorded at least every 3 months for the first 3 months, and every 6 months thereafter until 6 months, and bone marrow aspiration, biopsy, and chromosome examination were performed at least every 6 months to observe efficacy and safety.

### Conditions Module

**Conditions:**

- Aplastic Anemia

**Keywords:**

- Aplastic Anemia

- Luspatercept

- CsA

- randomized controlled study

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 58

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Drug: Luspatercept

- Drug: cyclosporine

**Label:** Luspatercept combined with cyclosporine

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 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.

**Intervention Names:**

- Drug: cyclosporine

**Label:** cyclosporine

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Luspatercept combined with cyclosporine

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

**Name:** Luspatercept

**Other Names:**

- cyclosporine

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Luspatercept combined with cyclosporine

- cyclosporine

**Description:** Cyclosporine (3-5mg/kg/day)

**Name:** cyclosporine

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Proportion of patients who achieved complete response, partial response and hematological response

**Measure:** overall response rate (ORR)

**Time Frame:** 6 month

#### Secondary Outcomes

**Description:** Proportion of patients who achieved complete response, partial response and hematological response

**Measure:** overall response rate (ORR)

**Time Frame:** 12 month

**Description:** Proportion of patients with adverse events

**Measure:** adverse event rate

**Time Frame:** 12 month

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Age ≥ 18 years
2. Hemoglobin level of 6-10 g/dL
3. 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))
4. No active infection
5. No other concurrent neoplasms (except in situ carcinoma)
6. Baseline liver and renal function within 1.5 times of normal value
7. No pregnancy or breastfeeding
8. Agree to sign informed consent form
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

Exclusion Criteria:

1. Congenital aplastic anemia
2. Presence of chromosomal aberrations
3. Cytogenetic evidence of clonal hematological myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML)
4. PNH clone ≥50%
5. Previous use of alemtuzumab, any ATG, or any dose of cyclosporine for immunosuppressive treatment
6. Previous hematopoietic stem cell transplant (HSCT)
7. Uncontrolled infection or bleeding under standard treatment
8. Allergy to rituximab, cyclosporine, or excipients
9. History of allergy to polyethylene glycol (PEG) 80
10. Active infection or cirrhosis of the liver or portal hypertension due to HIV, HCV, or HBV
11. 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
12. 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
13. Pregnant or lactating women
14. Participated in another clinical trial within 3 months

**Maximum Age:** 90 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Hanbing_li@sina.com.cn

**Name:** Bing Bing, PhD

**Phone:** 13601059938

**Role:** CONTACT

**Contact 2:**

**Email:** HQLin2012@163.com

**Name:** QLin Hu, PhD

**Phone:** 15810785167

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Beijing

**Contacts:**

***Contact 1:***

- **Email:** HQLin2012@163.com

- **Name:** QLin Hu

- **Phone:** 15810785167

- **Role:** CONTACT

***Contact 2:***

- **Name:** Bing Bing, PhD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** China

**Facility:** Peking Union Medical College Hospital

**State:** Beijing

**Zip:** 100730

#### Overall Officials

**Official 1:**

**Affiliation:** Peking Union Medical College Hospital

**Name:** Bing Bing, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Young NS. Aplastic anaemia. Lancet. 1995 Jul 22;346(8969):228-32. doi: 10.1016/s0140-6736(95)91273-8. No abstract available.

**PMID:** 7616805

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

**PMID:** 30354958

**Citation:** 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.

**PMID:** 28096088

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

**PMID:** 1813058

**Citation:** 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

**Citation:** 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

**Citation:** 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

**Citation:** 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

**Citation:** 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

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

**PMID:** 31939073

**Citation:** 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

**Citation:** Feld J, Navada SC, Silverman LR. Myelo-deception: Luspatercept & TGF-Beta ligand traps in myeloid diseases & anemia. Leuk Res. 2020 Oct;97:106430. doi: 10.1016/j.leukres.2020.106430. Epub 2020 Jul 30.

**PMID:** 32763582

**Citation:** Komrokji RS, Platzbecker U, Fenaux P, Zeidan AM, Garcia-Manero G, Mufti GJ, Santini V, Diez-Campelo M, Finelli C, Jurcic JG, Greenberg PL, Sekeres MA, DeZern AE, Savona MR, Shetty JK, Ito R, Zhang G, Ha X, Backstrom JT, Verma A. Luspatercept for myelodysplastic syndromes/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis. Leukemia. 2022 May;36(5):1432-1435. doi: 10.1038/s41375-022-01521-4. Epub 2022 Feb 26. No abstract available.

**PMID:** 35220402

**Citation:** Hellstrom-Lindberg E, Gulbrandsen N, Lindberg G, Ahlgren T, Dahl IM, Dybedal I, Grimfors G, Hesse-Sundin E, Hjorth M, Kanter-Lewensohn L, Linder O, Luthman M, Lofvenberg E, Oberg G, Porwit-MacDonald A, Radlund A, Samuelsson J, Tangen JM, Winquist I, Wisloff F; Scandinavian MDS Group. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol. 2003 Mar;120(6):1037-46. doi: 10.1046/j.1365-2141.2003.04153.x.

**PMID:** 12648074

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000080983

- Term: Bone Marrow Failure Disorders

- ID: D000001855

- Term: Bone Marrow Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M4070

- Name: Anemia

- Relevance: HIGH

- As Found: Anemia

- ID: M4071

- Name: Anemia, Aplastic

- Relevance: HIGH

- As Found: Aplastic Anemia

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2241

- Name: Bone Marrow Failure Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M13118

- Name: Pancytopenia

- Relevance: LOW

- As Found: Unknown

- ID: M5134

- Name: Bone Marrow Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T460

- Name: Aplastic Anemia

- Relevance: HIGH

- As Found: Aplastic Anemia

### Condition Browse Module - Meshes

- ID: D000000740

- Term: Anemia

- ID: D000000741

- Term: Anemia, Aplastic

### Intervention Browse Module - Ancestors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000935

- Term: Antifungal Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000003879

- Term: Dermatologic Agents

- ID: D000018501

- Term: Antirheumatic Agents

- ID: D000065095

- Term: Calcineurin Inhibitors

- ID: D000006397

- Term: Hematinics

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: Derm

- Name: Dermatologic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Hemat

- Name: Hematinics

### Intervention Browse Module - Browse Leaves

- ID: M18961

- Name: Cyclosporine

- Relevance: HIGH

- As Found: Target

- ID: M352828

- Name: Luspatercept

- Relevance: HIGH

- As Found: Catheter insertion

- ID: M6730

- Name: Cyclosporins

- Relevance: HIGH

- As Found: Target

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M6252

- Name: Clotrimazole

- Relevance: LOW

- As Found: Unknown

- ID: M11796

- Name: Miconazole

- Relevance: LOW

- As Found: Unknown

- ID: M4254

- Name: Antifungal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M7074

- Name: Dermatologic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M30452

- Name: Calcineurin Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M9485

- Name: Hematinics

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000016572

- Term: Cyclosporine

- ID: C000621232

- Term: Luspatercept

- ID: D000003524

- Term: Cyclosporins

### Misc Info Module

- Version Holder: 2024-05-31
