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

Primary Purpose

Leukemia

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Cytarabine
Busulfan
Cyclophosphamide
Me-CCNU
Rabbit antithymocyte globulin
Allogeneic HSCT
Cyclosporin A
Mycophenolate Mofetil
MTX
Sponsored by
First Affiliated Hospital of Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring hematopoietic stem cell transplantation

Eligibility Criteria

14 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sir Run Run Shaw Hospital, College of Medicine, Zhejiang UniversityRecruiting
  • The First Affiliated Hospital, College of Medicine, Zhejiang UniversityRecruiting
  • The Second Affiliated Hospital, College of Medicine, Zhejiang UniversityRecruiting
  • Zhejiang Provincial People's HospitalRecruiting
  • Jinhua Hospital of Zhejiang UniversityRecruiting
  • Ningbo Hospital of Zhejiang UniversityRecruiting
  • The Affiliated People's Hospital of Ningbo UniversityRecruiting
  • The First Affiliated Hospital of Wenzhou Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Non-first-degree donor

First-degree donor

Arm Description

Each patient receive graft from a non-first degree donor aged ≤40

Each patients receive graft from a first-degree donor aged >50

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.

Full Information

First Posted
September 7, 2020
Last Updated
February 19, 2023
Sponsor
First Affiliated Hospital of Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT04547049
Brief Title
A Study Comparing Haploidentical Hematopoietic Stem Cell Transplantations (HSCTs) From Young Non-first-degree and Older First-degree Donors in Hematological Malignancies
Official Title
An Open, Multi-center, Randomized Trial Comparing Haploidentical HSCTs From Young Non-first-degree and Older First-degree Donors in Hematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2020 (Actual)
Primary Completion Date
September 1, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
First Affiliated Hospital of Zhejiang University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
hematopoietic stem cell transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Non-first-degree donor
Arm Type
Active Comparator
Arm Description
Each patient receive graft from a non-first degree donor aged ≤40
Arm Title
First-degree donor
Arm Type
Active Comparator
Arm Description
Each patients receive graft from a first-degree donor aged >50
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
4 mg/m2/day administered IV day -10 through -9.
Intervention Type
Drug
Intervention Name(s)
Busulfan
Intervention Description
3.2 mg/kg/day administered IV day -8 through -6.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
1.8 g/m2/day administered IV day -5 through -4.
Intervention Type
Drug
Intervention Name(s)
Me-CCNU
Intervention Description
250mg/m2 once administered orally on day -3.
Intervention Type
Drug
Intervention Name(s)
Rabbit antithymocyte globulin
Intervention Description
1.5mg/kg/day administered IV day -5 through -2.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic HSCT
Intervention Description
Day 0
Intervention Type
Drug
Intervention Name(s)
Cyclosporin A
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Intervention Description
500 mg/day administered intravenously from day -9, ended in complete withdrawal on day +100.
Intervention Type
Drug
Intervention Name(s)
MTX
Intervention Description
15 mg/m2 administered intravenously on day +1, 10mg/m2 on day +3, +6, and +9.
Primary Outcome Measure Information:
Title
Cumulative incidence of transplant-related nonrelapse mortality (NRM)
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
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.
Time Frame
2 years
Title
Progression-free survival (PFS)
Description
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.
Time Frame
2 years
Title
Cumulative incidence of disease relapse or progression
Description
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.
Time Frame
2 years
Title
GVHD-free, relapse-free survival (GRFS)
Description
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.
Time Frame
2 years
Title
Cumulative incidence of acute grade II-IV GVHD
Description
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.
Time Frame
2 years
Title
Cumulative incidence of chronic GVHD
Description
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.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yi Luo, MD
Phone
86-13666609126
Email
luoyijr@zju.edu.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yishan Ye, MD
Phone
86-18268068056
Email
yeyishan@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yi Luo, MD
Organizational Affiliation
First Affiliated Hospital of Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University
City
Hangzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Haowen Xiao, MD
Facility Name
The First Affiliated Hospital, College of Medicine, Zhejiang University
City
Hangzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yi Luo
Email
luoyijr@zju.edu.cn
First Name & Middle Initial & Last Name & Degree
Yishan Ye
Email
yeyishan@hotmail.com
Facility Name
The Second Affiliated Hospital, College of Medicine, Zhejiang University
City
Hangzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yang Xu, MD
Facility Name
Zhejiang Provincial People's Hospital
City
Hangzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianping Lan, MD
Facility Name
Jinhua Hospital of Zhejiang University
City
Jinhua
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Huixian Hu, MD
Facility Name
Ningbo Hospital of Zhejiang University
City
Ningbo
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guifang Ouyang, MD
Facility Name
The Affiliated People's Hospital of Ningbo University
City
Ningbo
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ying Chen, MD
Facility Name
The First Affiliated Hospital of Wenzhou Medical University
City
Wenzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yi Chen, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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