BPC2001 for the Prevention of Acute Graft-Versus-Host Disease Following Haploidentical Stem Cell Transplantation

Inclusion Criteria36

• Male or female ages ≥18 and ≤ 65 years.
• Before the start of the trial, the subject or his/her guardian is sufficient to understand and voluntarily sign the written informed consent form (ICF).
• Subjects have a hematologic malignancy as defined below and are considered candidates for haplo-SCT:
• Acute leukemia with morphologic complete remission (acute myelogenous leukemia \[AML\] or acute lymphoblastic leukemia \[ALL\]);
• Myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or myeloproliferative neoplasm (MPN) with < 10% blasts in the bone marrow.
• Organ function tolerated for transplantation:
• Cardiac function: Left ventricular ejection fraction at rest ≥ 45%;
• Liver function: Total bilirubin < 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN. Subjects who have been diagnosed with Gilbert's syndrome or malignant disease involvement are allowed to have a total bilirubin value > 1.5 × ULN;
• Serum creatine < 2 mg/dL or estimated creatinine clearance > 50 mL/min calculated using the Cockcroft-Gault equation；
• Pulmonary function tests (PFTs): diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) and/or forced expiratory volume in 1 second (FEV1) ≥ 50%.
• Subject is suitable for myeloablative haplotype related donor transplant.
• Subject is suitable for receiving first alloHSCT.
• The transplant donor must meet the following criteria:
• Donor ages > 30 years; If the donor ages is equal to or less than 30 years, the donor should be female for male subject;
• High-resolution typing of human leukocyte antigen (HLA)-A, -B, -C, DR, and DQ are matched at least 5/10;
• Meet the criteria for peripheral blood stem cell (PBSC) donation;
• Donor's specific antibodies are negative, <2,000 MFI.
• Source of allografts: using G-CSF as the mobilizing agent to mobilize PBSC transplant; bone marrow or cord blood is not allowed.
• Karnofsky Performance Status (KPS) score ≥ 60 points.
• Is a Candidate for anti-GvHD prophylaxis, including ATG, calcineurin inhibitor (CsA or tacrolimus \[FK 506\]) in combination with MTX and MMF.
• Female subjects of childbearing potential must have a negative serum pregnancy test prior to enrollment and must have agreed to use a double barrier method of contraception from the time of signing the ICF to 90 days after the last dose of investigational drug.
• Male subjects must agree to use effective contraception from the time of signing the ICF to 90 days after the last dose of investigational drug.
• Has had received an investigational drug within 4 half-lives or within 14 days prior to HSCT, whichever is longer; or plans to participate in another clinical study prior to completion of all scheduled evaluations in this clinical study.
• Has other malignancies that are not controlled.
• Has evidence of active central nervous system (CNS) disease.
• Patients with uncontrolled active bacterial, viral, or fungal infections.
• Known history of human immunodeficiency virus (HIV) or positive HIV antibody test.
• Hepatitis B virus surface antigen (HBsAg) or hepatitis B virus core antibody (HBcAb) is positive, and the hepatitis B virus (HBV) DNA in peripheral blood is above the limit of quantification; or hepatitis C virus (HCV) antibody and peripheral HCV RNA are positive; or the syphilis TRUST test is positive.
• Pregnant or lactating females.
• Has undergone major surgery within 1 month prior to the first dose of investigational drug.
• In the opinion of the investigator, the subject has any other medical condition that renders the subject unsuitable for participation in the study.
• Has a history of uncontrolled autoimmune disease or on active treatment.
• Vaccinated with live or attenuated vaccine within 4 weeks prior to the first dose of investigational drug.
• History of myocardial infarction, unstable angina, acute coronary syndrome, congestive heart failure (New York Heart Society classification ≥ class Ⅲ), or clinically significant arrhythmia within 6 months prior to receiving the investigational drug.
• Plan to use prophylaxis donor lymphocyte infusion (DLI) therapy.
• The transplant donor is the subject's mother or collateral relative.