## Protocol Section
### Identification Module
**NCT ID:** NCT05669079

**Brief Title:** 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

#### Organization Study ID Info
**ID:** SOOCHOW-HY-2022-12-15
#### Organization
**Class:** OTHER
**Full Name:** The First Affiliated Hospital of Soochow University
### Status Module
#### Completion Date
**Date:** 2026-11-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-06-09

**Type:** ACTUAL

**Last Update Submit Date:** 2023-06-08

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-08-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-08-01

**Type:** ESTIMATED

**Status Verified Date:** 2022-12

#### Study First Post Date
**Date:** 2022-12-30
**Type:** ACTUAL
**Study First Submit Date:** 2022-12-19
**Study First Submit QC Date:** 2022-12-29
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** The First Affiliated Hospital of Soochow University

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- Poor Graft Function

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 100

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**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)

**Intervention Names:**

- Drug: decitabine

- Biological: umbilical cord blood

- Drug: Granulocyte-colony stimulating factor

- Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist

- Drug: Recombinant human erythropoietin

**Label:** Arm A

**Type:** EXPERIMENTAL

#### Arm Group 2

**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.

**Intervention Names:**

- Drug: Granulocyte-colony stimulating factor

- Drug: Recombinant human thrombopoietin / thrombopoietin receptor agonist

- Drug: Recombinant human erythropoietin

**Label:** Arm B

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Arm A

**Description:** 15 mg/m2 daily intravenously for consecutive 3 days

**Name:** decitabine

**Other Names:**

- Dec

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Arm A

**Description:** MNC ≥ 3\*108 cells; HLA compatibility ≥ 5/6

**Name:** umbilical cord blood

**Other Names:**

- UCB

**Type:** BIOLOGICAL

#### Intervention 3

**Arm Group Labels:**

- Arm A

- Arm B

**Description:** Granulocyte-colony stimulating factor will be used when absolute neutrophil count ≤ 1.5 × 109/L

**Name:** Granulocyte-colony stimulating factor

**Other Names:**

- G-CSF

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- Arm A

- Arm B

**Description:** Recombinant human thrombopoietin or thrombopoietin receptor agonist will be used when platelet count ≤ 30 × 109/L

**Name:** Recombinant human thrombopoietin / thrombopoietin receptor agonist

**Other Names:**

- rhTPO/TPO-RA

**Type:** DRUG

#### Intervention 5

**Arm Group Labels:**

- Arm A

- Arm B

**Description:** Recombinant human erythropoietin will be used when hemoglobin ≤ 85 g/L

**Name:** Recombinant human erythropoietin

**Other Names:**

- EPO

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** The rate of hematological improvement and hematological response of 2 arms

**Measure:** The treatment response

**Time Frame:** day +28

**Description:** The rate of overall survival

**Measure:** Survival

**Time Frame:** 1 year

#### Secondary Outcomes

**Description:** Number of participants with granulopoiesis, erythropoiesis and megakaryopoiesis recovery of bone marrow

**Measure:** Bone marrow recovery

**Time Frame:** day +28

**Description:** The rate of relapse and GVHD

**Measure:** relapse and GVHD

**Time Frame:** 3-month

**Description:** The rate of event free survival

**Measure:** Event free survival

**Time Frame:** 1-year

### Eligibility Module

**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.

**Maximum Age:** 65 Years

**Minimum Age:** 16 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** tangyaqiong@suda.edu.cn

**Name:** Yaqiong Tang

**Phone:** 18896588075

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** The First Affiliated Hospital of Soochow University

**Name:** Yue Han

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### 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.

**PMID:** 27088376

**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.

**PMID:** 16818281

**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.

**PMID:** 34492685

**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.

**PMID:** 33646303

**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.

**PMID:** 26181032

## Derived Section

### Intervention Browse Module - Ancestors

- ID: D000000964

- Term: Antimetabolites, Antineoplastic

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000000276

- Term: Adjuvants, Immunologic

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000006397

- Term: Hematinics

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: Analg

- Name: Analgesics

- Abbrev: Hemat

- Name: Hematinics

### Intervention Browse Module - Browse Leaves

- ID: M1697

- Name: Decitabine

- Relevance: HIGH

- As Found: Above

- ID: M207501

- Name: Chrysarobin

- Relevance: LOW

- As Found: Unknown

- ID: M1945

- Name: Lenograstim

- Relevance: HIGH

- As Found: Indicated

- ID: M314

- Name: Epoetin Alfa

- Relevance: HIGH

- As Found: Peak

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M3628

- Name: Adjuvants, Immunologic

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M9485

- Name: Hematinics

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000077209

- Term: Decitabine

- ID: D000068817

- Term: Epoetin Alfa

- ID: D000078224

- Term: Lenograstim

### Misc Info Module

- Version Holder: 2024-05-24
