A Study Comparing Haploidentical Hematopoietic Stem Cell Transplantations (HSCTs) From Young Non-first-degree and Older First-degree Donors in Hematological Malignancies
- Conditions
- Leukemia
- Interventions
- Registration Number
- NCT04547049
- Lead Sponsor
- First Affiliated Hospital of Zhejiang University
- 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 acute leukemias and MDS who are eligible to haploidentical HSCTs. 2 groups of patients will be enrolled with 88 in each group. The clinical criteria including survival, relapse, transplantation-related mortality will be monitored.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 176
- 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 ≥ 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
- The donor and recipient are HLA identical
- Has not donated blood products to recipient
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Non-first-degree donor Cytarabine 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. Non-first-degree donor Busulfan 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. Non-first-degree donor Cyclophosphamide 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. Non-first-degree donor Me-CCNU 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. Non-first-degree donor Rabbit antithymocyte globulin 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. Non-first-degree donor Allogeneic HSCT 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. Non-first-degree donor Cyclosporin A 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. Non-first-degree donor Mycophenolate Mofetil 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. Non-first-degree donor MTX 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. First-degree donor Cytarabine 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. First-degree donor Busulfan 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. First-degree donor Cyclophosphamide 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. First-degree donor Me-CCNU 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. First-degree donor Rabbit antithymocyte globulin 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. First-degree donor Allogeneic HSCT 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. First-degree donor Cyclosporin A 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. First-degree donor Mycophenolate Mofetil 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI. First-degree donor MTX 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: FluMel, TBF, FTM, Cy-TBI, Flu-TBI.
- Primary Outcome Measures
Name Time Method Cumulative incidence of transplant-related nonrelapse mortality (NRM) 2 years 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
Name Time Method Overall survival (OS) 2 years 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) 2 years 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 2 years 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) 2 years 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 180 days 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 2 years 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.
Trial Locations
- Locations (8)
The First Affiliated Hospital of Soochow University
🇨🇳Soochow, China
Xinqiao Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University
🇨🇳Chongqing, China
The First Affiliated Hospital of Ningbo University
🇨🇳Ningbo, China
Xiangya Hospital Central South University
🇨🇳Changsha, China
The First Affiliated Hospital, College of Medicine, Zhejiang University
🇨🇳Hangzhou, China
Zhejiang Provincial People's Hospital
🇨🇳Hangzhou, China
The First Affiliated Hospital of Nanjing Medical University
🇨🇳Nanjing, China
The Affiliated People's Hospital of Ningbo University
🇨🇳Ningbo, China