Clinical trial NCT05669079: Decitabine and Umbilical Cord Blood for Poor Graft Function Post Allo-HSCT
Official title: Decitabine and Umbilical Cord Blood for Poor Graft Function Post Allogenic Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Poor Graft Function
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2022-12-30
Enrollment: 100
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized trial aimed at validating the efficacy and safety of low-dose decitabine, together with umbilical cord blood in PGF post allo-HSCT patients.

Detailed description: Poor graft function (PGF), defined by the presence of multilineage cytopenias in the presence of 100% donor chimerism, is a serious complication of allogeneic stem cell transplant (allo-HSCT). Emerging evidence demonstrates that the inadequate stem cells infusion, bone marrow microenvironment and immune dysregulation play a crucial role in maintaining and regulating hematopoiesis. Current therapies remain debatable, including selected CD34+ cells infusion, mesenchymal stromal cells infusion, prophylactic N-acetyl cysteine administration, etc. Thereafter, the investigators conduct a randomized trial aiming at validating the efficacy and safety of low-dose decitabine, together with umbilical cord blood in PGF post allo-HSCT patients.

Patients were eligible if they were diagnosed as PGF at day 28 post-HSCT or later. PGF was defined as two or three cytopenias, absolute neutrophil count ≤ 1.5 × 109/L, platelet count ≤ 30 × 109/L, hemoglobin ≤ 85g/L, lasting for more than 14 consecutive weeks, in the presence of full donor chimerism and primary disease in remission without severe graft-versus- host disease (GVHD) and relapse.

Patients with the following conditions or diagnoses were excluded: allergic to decitabine or any components of frozen preservation of umbilical cord blood; active infections; uncontrolled GVHD; severe organ dysfunction; relapse of underlying malignancies; graft failure. Patients were also excluded if they had received decitabine or participated in other clinical trials within one month before screening.

Hematological improvement is defined as recovery of two or three blood lineages: absolute neutrophil count\>1.5 × 109/L, platelet count\>30 × 109/L, hemoglobin\>85g/L, without G-CSF, red blood cell or platelet infusion.

Hematological response is defined as recovery of three blood lineages: absolute neutrophil count\>2.5 × 109/L, platelet count\>60 × 109/L, hemoglobin\>100g/L, without G-CSF, red blood cell or platelet infusion.

No response: failed to achieve hematological improvement or response.

Eligibility criteria: Inclusion Criteria:

1. Diagnosed as PGF at day 28 post-HSCT or later. PGF was defined as two or three cytopenias, absolute neutrophil count ≤ 1.5 × 109/L, platelet count ≤ 30 × 109/L, hemoglobin ≤ 85g/L, lasting for more than 2 consecutive weeks;
2. Full donor chimerism;
3. Primary disease in remission;
4. No severe GVHD and relapse.

Exclusion Criteria:

1. Allergic to decitabine or any components of frozen preservation of umbilical cord blood;
2. Active infections;
3. Uncontrolled GVHD;
4. Severe organ dysfunction;
5. Relapse of underlying malignancies;
6. Graft failure;
7. Received decitabine or participated in other clinical trials within one month before screening.

Primary outcomes:
measure: The treatment response
timeFrame: day +28
measure: Survival
timeFrame: 1 year
Secondary outcomes:
measure: Bone marrow recovery
timeFrame: day +28
measure: relapse and GVHD
timeFrame: 3-month
measure: Event free survival
timeFrame: 1-year
Other outcomes:
Locations:
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Yue Han
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alchalby H, Yunus DR, Zabelina T, Ayuk F, Kroger N. Incidence and risk factors of poor graft function after allogeneic stem cell transplantation for myelofibrosis. Bone Marrow Transplant. 2016 Sep;51(9):1223-7. doi: 10.1038/bmt.2016.98. Epub 2016 Apr 18.
citation: Larocca A, Piaggio G, Podesta M, Pitto A, Bruno B, Di Grazia C, Gualandi F, Occhini D, Raiola AM, Dominietto A, Bregante S, Lamparelli T, Tedone E, Oneto R, Frassoni F, Van Lint MT, Pogliani E, Bacigalupo A. Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica. 2006 Jul;91(7):935-40.
citation: Prabahran A, Koldej R, Chee L, Ritchie D. Clinical features, pathophysiology, and therapy of poor graft function post-allogeneic stem cell transplantation. Blood Adv. 2022 Mar 22;6(6):1947-1959. doi: 10.1182/bloodadvances.2021004537.
citation: Tang Y, Chen J, Liu Q, Chu T, Pan T, Liang J, He XF, Chen F, Yang T, Ma X, Wu X, Hu S, Cao X, Hu X, Hu J, Liu Y, Qi J, Shen Y, Ruan C, Han Y, Wu D. Low-dose decitabine for refractory prolonged isolated thrombocytopenia after HCT: a randomized multicenter trial. Blood Adv. 2021 Mar 9;5(5):1250-1258. doi: 10.1182/bloodadvances.2020002790.
citation: Han Y, Tang Y, Chen J, Liang J, Ye C, Ruan C, Wu D. Low-Dose Decitabine for Patients With Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation: A Pilot Therapeutic Study. JAMA Oncol. 2015 May;1(2):249-51. doi: 10.1001/jamaoncol.2014.316. No abstract available.