Decitabine and Umbilical Cord Blood for Poor Graft Function Post Allo-HSCT

Soochow University

Status and phase: Not yet enrolling; Phase 3

Conditions: Poor Graft Function

Treatments: Biological: umbilical cord blood; Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist; Drug: decitabine; Drug: Recombinant human erythropoietin; Drug: Granulocyte-colony stimulating factor

Study type: Interventional

Funder types: Other

Identifiers

NCT05669079

SOOCHOW-HY-2022-12-15

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 16 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

100 participants in 2 patient groups

Arm A

Experimental group

Description:

decitabine (Chia Tai Tianqing Pharma) 15 mg/m2 daily intravenously for consecutive 3 days (day 1 to day 3), combined with umbilical cord blood infusion (day 8)

Treatment:

Drug: Recombinant human erythropoietin

Drug: Granulocyte-colony stimulating factor

Drug: decitabine

Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist

Biological: umbilical cord blood

Arm B

Active Comparator group

Description:

Supportive therapy: G-CSF for patients with absolute neutrophil count ≤ 1.5 × 109/L, rhTPO/TPO-R with platelet count ≤ 30 × 109/L, EPO with hemoglobin ≤ 85g/L.

Treatment:

Drug: Recombinant human erythropoietin

Drug: Granulocyte-colony stimulating factor

Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist