Clinical trial NCT05925504: The Tapering Dose of Luspatercept in Patients With Lower-risk Myelodysplastic Syndromes
Official title: Safety and Efficacy Study of the Tapering Dose of Luspatercept in Patients With Lower-risk Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lower Risk MDS Per IPSS-R
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Beijing Health Alliance Charitable Foundation
First posted: 2023-06-29
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective, single center, single-arm, phase 2 study. The aim of this study is to evaluate the efficacy and safety of Luspatercept for Patients with Lower-risk Myelodysplastic Syndromes (MDS).


Eligibility criteria: Inclusion Criteria:

* Male or female age ≥ 18 years
* Subject has diagnosis of MDS according to WHO classification that meets IPSS-R score ≤3.5
* Hemoglobin \< 100g/L at baseline
* Refractory or intolerant to prior ESA treatment or EPO≥500U/L
* ECOG performance status ≤2
* Willing and able to comply with the requirements for this study and written informed consent.

Exclusion Criteria:

* Platelet counts \< 50 x 10\^9/L
* Previously treated with either luspatercept or sotatercept
* Use any of the following prior to this study

  * Immunomodulatory drugs such as lenalidomide \[IMiD\] for ≥4 weeks
  * Immunosuppressive therapy \[IST\] for ≥4 weeks
  * Demethylating agents \[HMA\] ≥ 1 cycle of treatment
* MDS associated with del 5q cytogenetic abnormality
* Secondary MDS, i.e. MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.
* Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding.
* Prior allogeneic or autologous stem cell transplant.
* Prior history of malignancies, other than MDS, unless the subject is 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, superficial bladder cancer, prostate intraepithelial neoplasia, carcinoma in situ of the cervix or other indolent tumors.
* Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment), known human immunodeficiency virus (HIV), known evidence of active infectious hepatitis B, and/or known evidence of active hepatitis C.
* Clinically significant cardiac disease, including any of the follow: uncontrolled angina pectoris, myocardial infarction, unstable cardiac arrhythmias, congestive heart failure and New York Heart Association (NYHA) grade 2-4 cardiac failure.
* Abnormal liver function: two consecutive examinations with an interval of ≥1 week suggest that ALT and AST are 2.5 times higher than the upper limit of normal values
* Renal impairment: creatinine clearance \<60ml/min
* Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study, including clinically significant cardiac diseases, refractory hypertension, metabolic disorders and other diseases that seriously affect the function of the gastrointestinal tract.
* Had a history of any psychiatric diseases, cerebrovascular disease or cognitive sequelae of head injury.
* Major surgery within 8 weeks prior to this study. Subjects must be completely recovered from any previous surgery prior to this study.
* Received attenuated vaccine in 4 weeks before enrollment.
* Participation in another clinical trial within 4 weeks before the start of this trial.
* History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the luspatercept.
* Pregnant or breast-feeding patients
* Patients considered to be ineligible for the study by the investigator for reasons other than the above.

Primary outcomes:
measure: Proportion of subjects achieving hematologic improvement - erythroids (HI-E) according to IWG 2006 criteria
timeFrame: within 12 weeks
Secondary outcomes:
measure: Proportion of subjects achieving RBC-TI according to IWG 2006 criteria
timeFrame: within 12 weeks
measure: Median time to HI-E or RBC-TI
timeFrame: within 12 weeks
measure: Mean change in serum ferritin
timeFrame: within 12 weeks
measure: Incidence of the adverse event
timeFrame: within 12 weeks
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Regenerative Medicine Center
state: Tianjin
Study officials:
References: