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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04547049
• Other study ID #: NFD-001
• Status: Recruiting
• Phase: Phase 3
• Start date: September 1, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2023
• Source: First Affiliated Hospital of Zhejiang University
• Contact: Yi Luo, MD
• Phone: 86-13666609126
• Email: luoyijr[@]zju.edu.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 ALL, AML, MDS and NHL who are eligible to haploidentical HSCTs. 2 groups of patients will be enrolled with 80 in each group. The clinical criteria including survival, relapse, transplantation-related mortality will be monitored.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: December 31, 2025
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 60 Years

Eligibility

Patient Inclusion Criteria:

• Patient age 14-60 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, with <5% bone marrow blasts before HSCT

ALL in remission, defined as <5% bone marrow blasts morphologically

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

NHLs (including diffuse large B-cell lymphoma, lymphoblastic lymphoma, Burkitt lymphoma, peripheral T-cell lymphoma, and NK or NK-T cell lymphoma) which are relapsed/refractory OR in CR2 or beyond

• 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

• 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 (ß-HCG+) or breast feeding

• Patients with a psychiatric history

• ECOG performance status = 3

• 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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Leukemia

Intervention

Drug:
• Cytarabine
4 mg/m2/day administered IV day -10 through -9.
• Busulfan
3.2 mg/kg/day administered IV day -8 through -6.
• Cyclophosphamide
1.8 g/m2/day administered IV day -5 through -4.
• Me-CCNU
250mg/m2 once administered orally on day -3.
• Rabbit antithymocyte globulin
1.5mg/kg/day administered IV day -5 through -2.

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.
• Mycophenolate Mofetil
500 mg/day administered intravenously from day -9, ended in complete withdrawal on day +100.
• MTX
15 mg/m2 administered intravenously on day +1, 10mg/m2 on day +3, +6, and +9.

Locations

Country	Name	City	State
China	Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University	Hangzhou
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou
China	The Second Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou
China	Zhejiang Provincial People's Hospital	Hangzhou
China	Jinhua Hospital of Zhejiang University	Jinhua
China	Ningbo Hospital of Zhejiang University	Ningbo
China	The Affiliated People's Hospital of Ningbo University	Ningbo
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital of Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	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	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
Secondary	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
Secondary	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
Secondary	Cumulative incidence of acute grade II-IV 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.	2 years
Secondary	Cumulative incidence of 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