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

Official title

An Open-Label, Single-Arm, Phase Ⅱb Clinical Study of BPC2001 for the Prevention of Acute Graft-Versus-Host Disease Following Haploidentical Stem Cell Transplantation

Overview

A Phase IIb open label study evaluates the safety and efficacy of repeat doses of BPC2001 in combination with standard of care treatment for the prevention of acute graft-vs-host-disease (aGvHD) in subjects following Haploidentical Stem Cell Transplantation (Haplo-SCT).

Detailed description

This is an open-label, single center, single-arm study to evaluate six weekly doses of BPC2001 in combination with standard of care treatment (Beijing Protocol) for the prevention of aGvHD in subjects following Haplo-SCT. The study includes a Safety Run-in Phase to assess the safety and tolerability of 30 days DLT after the first dose of BPC2001 followed by an Expansion Phase in which the efficacy of 6 weekly doses of BPC2001 in addition to standard of care for GvHD prophylaxis will be assessed.

Interventions

• Drug BPC-2001
  Subjects will receive 6 weekly doses of BPC2001, 100 μg/kg via IV administration after completion of Haplo-SCT.

Primary outcome measures

• Grades II-IV aGVHD [Time frame: Day 100 after the last infusion of stem cell]
• AE of BPC2001 in addition to the graft-versus-host disease (GvHD) prophylaxis regimen [Time frame: 1 year post-transplant]
• SAE of BPC2001 in addition to the graft-versus-host disease (GvHD) prophylaxis regimen [Time frame: 1 year post-transplant]
• Lab test values of BPC2001 in addition to the graft-versus-host disease (GvHD) prophylaxis regimen [Time frame: 1 year post-transplant]
• Vital sign of BPC2001 in addition to the graft-versus-host disease (GvHD) prophylaxis regimen [Time frame: 1 year post-transplant]
• Graft failure of BPC2001 in addition to the graft-versus-host disease (GvHD) prophylaxis regimen [Time frame: 1 year post-transplant]

Secondary outcome measures (12)

• Grades II-IV aGVHD [Time frame: Day 180 post-transplant]
• Total and moderate-severe cGvHD [Time frame: Day 180 and 1 year post-transplant]
• Non-relapse Mortality (NRM) Rates [Time frame: Day 100, Day 180 and 1 year post-transplant]
• Disease-free Survival (DFS) [Time frame: Day 180 and 1 year post-transplant]
• GvHD-free, Relapse Free Survival (GRFS) [Time frame: Day 180 and 1 year post-transplant]
• Overall Survival (OS) [Time frame: Day 180 and 1 year post-transplant]
• PK Profile_Cmax after a single dose of BPC2001 [Time frame: Day 0 through Day 35]
• PK Profile_Tmax after a single dose of BPC2001 [Time frame: Day 0 through Day 35]
• PK Profile_AUC0-t after a single dose of BPC2001 [Time frame: Day 0 through Day 35]
• PK Profile_AUC0-inf after a single dose of BPC2001 [Time frame: Day 0 through Day 35]
• PK Profile_t1/2 after a single dose of BPC2001 [Time frame: Day 0 through Day 35]
• PK Profile_CL after a single dose of BPC2001 [Time frame: Day 0 through Day 35]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

Any subjects who meet any of the following criteria will be excluded from study entry:

• Has had any other prior organ transplantation.
• Planned use of any additional or alternative drugs for GvHD prophylaxis than listed in the inclusion criteria.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

China · 1 center

• Peking University People's Hospital — Beijing

Publications

• 7.General Office of National Health Commission. Clinical Application Management Standards for Allogeneic Hematopoietic Stem Cell Transplantation Technology (2022 Edition).
• Ciurea SO, Al Malki MM, Kongtim P, Fuchs EJ, Luznik L, Huang XJ, Ciceri F, Locatelli F, Aversa F, Castagna L, Bacigalupo A, Martelli M, Blaise D, Ben Soussan P, Arnault Y, Handgretinger R, Roy DC, O'Donnell PV, Bashey A, Solomon S, Romee R, Gayoso J, Lazarus HM, Ballen K, Savani BN, Mohty M, Nagler A. The European Society for Blood and Marrow Transplantation (EBMT) consensus recommendations for do PMID 30833742
• Wang Y, Chang YJ, Xu LP, Liu KY, Liu DH, Zhang XH, Chen H, Han W, Chen YH, Wang FR, Wang JZ, Chen Y, Yan CH, Huo MR, Li D, Huang XJ. Who is the best donor for a related HLA haplotype-mismatched transplant? Blood. 2014 Aug 7;124(6):843-50. doi: 10.1182/blood-2014-03-563130. Epub 2014 Jun 10. PMID 24916508
• Duramad O, Laysang A, Li J, Ishii Y, Namikawa R. Pharmacologic expansion of donor-derived, naturally occurring CD4(+)Foxp3(+) regulatory T cells reduces acute graft-versus-host disease lethality without abrogating the graft-versus-leukemia effect in murine models. Biol Blood Marrow Transplant. 2011 Aug;17(8):1154-68. doi: 10.1016/j.bbmt.2010.11.022. Epub 2010 Dec 8. PMID 21145405
• Socie G, Blazar BR. Acute graft-versus-host disease: from the bench to the bedside. Blood. 2009 Nov 12;114(20):4327-36. doi: 10.1182/blood-2009-06-204669. Epub 2009 Aug 27. PMID 19713461
• Hematopoietic Stem Cell Application Group, Chinese Society of Hematology, Chinese Medical Association. [Chinese expert consensus on the diagnosis and treatment of acute graft-versus-host disease after hematopoietic stem cell transplantation (2024)]. Zhonghua Xue Ye Xue Za Zhi. 2024 Jun 14;45(6):525-533. doi: 10.3760/cma.j.cn121090-20240608-00214. Chinese. PMID 39134482
• 1. Huang Xiaojun. Haploidentical Hematopoietic Stem Cell Transplantation Beijing Protocol, Chinese Journal of Organ Transplantation. 2017;38(2): 65-68.

Identifiers

NCT: NCT07246031 · BPC2001-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗