Leukemia, MDS
Conditions
Keywords
hematopoietic stem cell transplantation
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 116 in each group. The clinical criteria including survival, relapse, transplantation-related mortality will be monitored.
Interventions
DRUGCytarabine
4 mg/m2/day administered IV day -10 through -9.
DRUGBusulfan
3.2 mg/kg/day administered IV day -8 through -6.
DRUGCyclophosphamide
1.8 g/m2/day administered IV day -5 through -4.
DRUGMe-CCNU
250mg/m2 once administered orally on day -3.
Between 6mg/kg total dose administered IV day -5 through -2 AND 7.5mg/kg total dose administered IV day -5 through -2.
PROCEDUREAllogeneic HSCT
Day 0
DRUGCyclosporin 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.
DRUGMycophenolate Mofetil
500 mg/day administered intravenously from day -9, ended in complete withdrawal on day +100.
DRUGMTX
15 mg/m2 administered intravenously on day +1, 10mg/m2 on day +3, +6, and +9.
Sponsors
First Affiliated Hospital of Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
Patient Inclusion Criteria: * 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 ≥ 2 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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 total acute and grade II-IV acute 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 total and and moderate-severe 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. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYi Luo, MD
First Affiliated Hospital of Zhejiang University
Outcome results
None listed