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: Recruiting
• Conditions: Leukemia
• Intervention / Treatment: Drug: Cytarabine; Drug: Busulfan; Drug: Cyclophosphamide; Drug: Me-CCNU; Drug: Rabbit antithymocyte globulin; Procedure: Allogeneic HSCT; Drug: Cyclosporin A; Drug: Mycophenolate Mofetil; Drug: MTX

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 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.

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yi Luo, MD; Phone Number: 86-13666609126; Email: luoyijr@zju.edu.com
• Study Contact Backup: Name: Yishan Ye, MD; Phone Number: 86-18268068056; Email: yeyishan@hotmail.com

Study Locations

• China
  • Hangzhou, China
    • Recruiting
    • Sir Run Run Shaw Hospital, College of medicine, Zhejiang University
    • Contact: Haowen Xiao, MD
  • Hangzhou, China
    • Recruiting
    • Zhejiang Provincial People's Hospital
    • Contact: Jianping Lan, MD
  • Hangzhou, China
    • Recruiting
    • The First Affiliated Hospital, College of Medicine, Zhejiang University
    • Contact: Yi Luo; Email: luoyijr@zju.edu.cn
    • Contact: Yishan Ye; Email: yeyishan@hotmail.com
  • Hangzhou, China
    • Recruiting
    • The Second Affiliated Hospital, College of Medicine, Zhejiang University
    • Contact: Yang Xu, MD
  • Jinhua, China
    • Recruiting
    • Jinhua Hospital of Zhejiang University
    • Contact: Huixian Hu, MD
  • Ningbo, China
    • Recruiting
    • Ningbo Hospital of Zhejiang University
    • Contact: Guifang Ouyang, MD
  • Ningbo, China
    • Recruiting
    • The Affiliated People's Hospital of Ningbo University
    • Contact: Ying Chen, MD
  • Wenzhou, China
    • Recruiting
    • The First Affiliated Hospital of Wenzhou Medical University
    • Contact: Yi Chen, MD

Participation Criteria

Eligibility Criteria

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

Description

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 (β-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

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	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.; Drug: 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.; 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.
Active Comparator: First-degree donor; Each patients receive graft from a first-degree donor aged >50	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.; Drug: 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.; 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.

What is the study measuring?

Primary 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

Secondary 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
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 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
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

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 (Anticipated): September 1, 2025
• Study Completion (Anticipated): December 31, 2025

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 (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 19, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Cyclophosphamide; Cytarabine; Mycophenolic Acid; Busulfan; Thymoglobulin; Antilymphocyte Serum; Cyclosporine; Cyclosporins
• 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