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

NCT04547049 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: NFD-001
• Study Type: interventional
• Target: 232
• Locations: 1 country
• Sites: 8

Brief Summary

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

Conditions

Leukemia; MDS

Keywords

hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Progression-free survival (PFS)

  2 years

• Cumulative incidence of transplant-related nonrelapse mortality (NRM)

  2 years

• Cumulative incidence of disease relapse or progression

  2 years

• GVHD-free, relapse-free survival (GRFS)

  2 years

• Cumulative incidence of total acute and grade II-IV acute GVHD

  180 days

Study Arms (2)

Non-first-degree donor

ACTIVE COMPARATOR

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; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Me-CCNU; Drug: Rabbit antithymocyte globulin; Procedure: Allogeneic HSCT; Drug: Cyclosporin A; Drug: Mycophenolate Mofetil; Drug: MTX

First-degree donor

ACTIVE COMPARATOR

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; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Me-CCNU; Drug: Rabbit antithymocyte globulin; Procedure: Allogeneic HSCT; Drug: Cyclosporin A; Drug: Mycophenolate Mofetil; Drug: MTX

Interventions

Cytarabine DRUG

4 mg/m2/day administered IV day -10 through -9.

First-degree donor; Non-first-degree donor

Busulfan DRUG

3.2 mg/kg/day administered IV day -8 through -6.

First-degree donor; Non-first-degree donor

Cyclophosphamide DRUG

1.8 g/m2/day administered IV day -5 through -4.

First-degree donor; Non-first-degree donor

Me-CCNU DRUG

250mg/m2 once administered orally on day -3.

First-degree donor; Non-first-degree donor

Rabbit antithymocyte globulin DRUG

Between 6mg/kg total dose administered IV day -5 through -2 AND 7.5mg/kg total dose administered IV day -5 through -2.

First-degree donor; Non-first-degree donor

Allogeneic HSCT PROCEDURE

Day 0

First-degree donor; Non-first-degree donor

Cyclosporin A DRUG

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.

First-degree donor; Non-first-degree donor

Mycophenolate Mofetil DRUG

500 mg/day administered intravenously from day -9, ended in complete withdrawal on day +100.

First-degree donor; Non-first-degree donor

MTX DRUG

15 mg/m2 administered intravenously on day +1, 10mg/m2 on day +3, +6, and +9.

First-degree donor; Non-first-degree donor

Eligibility Criteria

• Age: 13 Years - 78 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (8)

Xiangya Hospital Central South University

Changsha, China

Location

Xinqiao Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University

Chongqing, China

Location

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, China

Location

Zhejiang Provincial People's Hospital

Hangzhou, China

Location

The First Affiliated Hospital of Nanjing Medical University

Nanjing, China

Location

The Affiliated People's Hospital of Ningbo University

Ningbo, China

Location

The First Affiliated Hospital of Ningbo University

Ningbo, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, China

Location

MeSH Terms

Conditions

Leukemia

Interventions

Cytarabine; Busulfan; Cyclophosphamide; Semustine; thymoglobulin; Cyclosporine; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Lomustine; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Yi Luo, MD

  First Affiliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: September 7, 2020
• First Posted: September 14, 2020
• Study Start: September 1, 2020
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: April 9, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (8)