A Study Comparing Haploidentical Hematopoietic Stem Cell Transplantations (HSCTs) From Young Non-first-degree and Older First-degree Donors in Hematological Malignancies

An Open, Multi-center, Randomized Trial Comparing Haploidentical HSCTs From Young Non-first-degree and Older First-degree Donors in Hematological Malignancies

An open, multi-center, randomized trial comparing haploidentical HSCTs from young non-first-degree and older first-degree donors in hematological malignancies

Study Overview

• Status: Active, not recruiting
• Conditions: Leukemia; MDS
• Intervention / Treatment: Drug: Cytarabine; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Me-CCNU; Procedure: Allogeneic HSCT; Drug: Cyclosporin A; Drug: Mycophenolate Mofetil; Drug: MTX; Drug: Rabbit antithymocyte globulin

Detailed Description

This is an open, multi-center, randomized trial comparing the clinical outcomes of haploidentical HSCTs from young non-first-degree and older first-degree donors in hematological malignancies. This study is indicated for patients with hematological malignancies including acute leukemias and MDS who are eligible to haploidentical HSCTs. 2 groups of patients will be enrolled with 116 in each group. The clinical criteria including survival, relapse, transplantation-related mortality will be monitored.

• Study Type: Interventional
• Enrollment (Estimated): 232
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Changsha, China
    • Xiangya Hospital Central South University
  • Chongqing, China
    • Xinqiao Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University
  • Hangzhou, China
    • Zhejiang Provincial People's Hospital
  • Hangzhou, China
    • The First Affiliated Hospital, College of Medicine, Zhejiang University
  • Nanjing, China
    • The First Affiliated Hospital of Nanjing Medical University
  • Ningbo, China
    • The Affiliated People's Hospital of Ningbo University
  • Ningbo, China
    • The First Affiliated Hospital of Ningbo University
  • Suzhou, China
    • The First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 60 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Patient Inclusion Criteria:

• Patient age 13-78 years
• Absence of a suitable HLA identical related or unrelated hematopoietic stem cell donor
• Absence of a suitable partially HLA-mismatched (haploidentical), first-degree related donor aged between 18 and 50
• Presence of both HLA haploidentical young non-first-degree (age ≤ 40) and older first-degree (age >50) donors

Eligible diagnoses:

AML（excluding APL） with at least one of the following:

• median- or high- risk according to the WHO prognostic stratification system
• failure to achieve CR after 2 cycles of induction chemotherapy
• AML arising from MDS or a myeloproliferative disorder, or secondary AML
• patients in CR2 or beyond

Mixed-phenotype acute leukemia (MPAL) in morphological remission Acute lymphoblastic leukemia (T or B) in morphological remission

MDS with at least one of the following:

• IPSS score of INT-2 or greater

• IPSS score of INT-1 with life-threatening cytopenias, including those generally requiring greater than weekly transfusions

  • A first allo-HCT
  • Adequate end-organ function
  • ECOG performance status < 2
  • No other contraindications for HSCT
  • Signature of the informed consent

Patient Exclusion Criteria

• Availability of suitable HLA identical related or unrelated hematopoietic stem cell donors
• Availability of suitable partially HLA-mismatched (haploidentical), first-degree related donor aged between 18 and 50
• Not the first allo-HCT
• Presence of uncontrolled bacterial, viral, or fungal infection
• Patients with severe heart, lung, liver and kidney insufficiency
• HIV-positive patients
• Women of childbearing potential who are pregnant (β-HCG+) or breast feeding
• Patients with a psychiatric history
• ECOG performance status ≥ 2
• Patients with malignancies other than the primary disease
• Refusal to sign the informed consent

Donor Inclusion Criteria:

• The donor and recipient must be HLA haploidentical
• Meets institutional selection criteria and medically fit to donate
• Lack of recipient anti-donor HLA antibody

Donor Exclusion Criteria:

• The donor and recipient are HLA identical
• Has not donated blood products to recipient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Non-first-degree donor; Each patient receive graft from a non-first degree donor aged ≤40 Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: TBF, FluMel, FBM, Cy-TBI, Flu-TBI.	Drug: Cytarabine; 4 mg/m2/day administered IV day -10 through -9.; Drug: Busulfan; 3.2 mg/kg/day administered IV day -8 through -6.; Drug: Cyclophosphamide; 1.8 g/m2/day administered IV day -5 through -4.; Drug: Me-CCNU; 250mg/m2 once administered orally on day -3.; Procedure: Allogeneic HSCT; Day 0; Drug: Cyclosporin A; 2.5 mg/kg/day administered intravenously from day -7, target: 200-300ng/mL. Usually tapered during the second month, and ended in complete withdrawal during the ninth month after transplantation.; Drug: Mycophenolate Mofetil; 500 mg/day administered intravenously from day -9, ended in complete withdrawal on day +100.; Drug: MTX; 15 mg/m2 administered intravenously on day +1, 10mg/m2 on day +3, +6, and +9.; Drug: Rabbit antithymocyte globulin; Between 6mg/kg total dose administered IV day -5 through -2 AND 7.5mg/kg total dose administered IV day -5 through -2.
Active Comparator: First-degree donor; Each patients receive graft from a first-degree donor aged >50 Conditoning regimens are decided by each center accoding to disease risk, patient age & status, and cormobidity index.The centers are required to use the same principle when treating NFD and FD patients. The used protocol in the current study included: For MAC: use BU-CY-based (described in detail) For RIC: use BUFlu: Drug: Fludarabine 30 mg/m²/kg, administered IV d-10 through d-5. Drug: Busulfan, 3.2 mg/kg/day administered IV day -6 (BU2) or -7 through -5 (BU3). Other conditioning regimen may include: TBF, FluMel, FBM, Cy-TBI, Flu-TBI.	Drug: Cytarabine; 4 mg/m2/day administered IV day -10 through -9.; Drug: Busulfan; 3.2 mg/kg/day administered IV day -8 through -6.; Drug: Cyclophosphamide; 1.8 g/m2/day administered IV day -5 through -4.; Drug: Me-CCNU; 250mg/m2 once administered orally on day -3.; Procedure: Allogeneic HSCT; Day 0; Drug: Cyclosporin A; 2.5 mg/kg/day administered intravenously from day -7, target: 200-300ng/mL. Usually tapered during the second month, and ended in complete withdrawal during the ninth month after transplantation.; Drug: Mycophenolate Mofetil; 500 mg/day administered intravenously from day -9, ended in complete withdrawal on day +100.; Drug: MTX; 15 mg/m2 administered intravenously on day +1, 10mg/m2 on day +3, +6, and +9.; Drug: Rabbit antithymocyte globulin; Between 6mg/kg total dose administered IV day -5 through -2 AND 7.5mg/kg total dose administered IV day -5 through -2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of transplant-related nonrelapse mortality (NRM)	All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.	2 years
Progression-free survival (PFS)	All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.	2 years
Cumulative incidence of disease relapse or progression	All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.	2 years
GVHD-free, relapse-free survival (GRFS)	All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression. GRFS is defined as survival with no evidence of relapse/progression, grade III to IV aGVHD, and systemic therapy-requiring cGVHD.	2 years
Cumulative incidence of total acute and grade II-IV acute GVHD	Date of symptom onset, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II or higher acute GVHD and grade III-IV acute GVHD will be recorded.	180 days
Cumulative incidence of total and and moderate-severe chronic GVHD	Date of symptom onset, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of chronic GVHD and severe chronic GVHD will be recorded.	2 years

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Investigators: Principal Investigator: Yi Luo, MD, First affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: September 7, 2020
• First Submitted That Met QC Criteria: September 7, 2020
• First Posted (Actual): September 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 4, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia; Peptides; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons, Acyclic; Hydrocarbons; Acids, Acyclic; Carboxylic Acids; Polycyclic Compounds; Amides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Alkanes; Alcohols; Butylene Glycols; Glycols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Sulfonic Acids; Sulfur Acids; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Nucleosides; Arabinonucleosides; Macrocyclic Compounds; Peptides, Cyclic; Caproates; Cyclosporins; Nitrosourea Compounds; Urea; Nitroso Compounds; Lomustine; Cyclophosphamide; Cytarabine; Mycophenolic Acid; Cyclosporine; Busulfan; Semustine; thymoglobulin
• Other Study ID Numbers: NFD-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No