Combined Haploidentical and Umbilical Cord Blood Allogeneic Stem Cell Transplantation in Patients With Acute Leukemia

Study Overview
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Brief Summary
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Allogeneic stem cell transplantation (Allo-HSCT) is the effective and even the only treatment option for acute leukemia. The haplo-hematopoietic stem cell transplantation(haplo-HSCT) and GIAC protocol have crossed HLA barrier and helped more patients find donors. However, the engraftment failure and incidence of graft-versus-host disease(GVHD) limit the prognosis of patients who receive the haplo-HSCT. It is believed that Combined haploidentical and umbilical cord blood allogeneic stem cell transplantation improved hematopoietic reconstitution and reduced the incidence of GVHD, there is still no consensus about the efficacy and safety of this kind of therapy. This prospective, randomized and controlled study is to investigate the efficacy and safety of Combined haploidentical and umbilical cord blood allogeneic stem cell transplantation

Detailed Description
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This prospective, randomized and controlled study is to investigate the efficacy and safety of Combined haploidentical and umbilical cord blood allogeneic stem cell transplantation. Investigators will recruit 116 patients with acute leukemia, with 58 of them entering the haplo-HSCT group and receiving haploidentical hematopoietic stem cell transplantation, while the other 58 entering the combined haploidentical and umbilical cord blood allogeneic stem cell transplantation group and receiving haploidentical and umbilical cord blood allogeneic stem cell transplantation at the same day. Then primary outcomes including overall survival and disease free survival, as well secondary outcomes such as cumulative relapse incidence and cumulative incidence of engraftment will be measured during 12 months after the intervention being finished.

Official Title
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The Efficacy and Safety of Combined Haploidentical and Umbilical Cord Blood Allogeneic Stem Cell Transplantation in Patients With Acute Leukemia.

Conditions
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Acute Leukemia

Intervention / Treatment
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* Procedure: Combined haploidentical and umbilical cord blood allogeneic stem cell transplantation
* Procedure: haploidentical hematopoietic stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 16-65 years inclusive. Diagnosed as acute leukemia, planning to receive haplo-HSCT Eastern Cooperative Oncology Group (ECOG) Performance status 0-2 Presence of an available haploidentical donor Signing written informed consent and agreeing with taking designated umbilical cord blood Exclusion Criteria: Uncontrolled infections less than 4 weeks prior to enrollment Secondary malignancy Psychiatric illness that would limit compliance with study requirements Impairment of heart, hepatic or renal function to such an extent that the patient, in the opinion of the investigator, will be exposed to an excessive risk if entered into this clinical study Allergic to blood products Other causes which are not suitable for the trial in investigator's consideration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Haplo-HSCT group<br>58 patients will be involved in this group | Procedure: haploidentical hematopoietic stem cell transplantation<br>* Receive haploidentical hematopoietic stem cell transplantation (HLA 6-10/10)<br>|
| Experimental: Combined haploidentical and umbilical cord blood allogeneic stem cell transplantation group<br>58 patients will be involved in this group | Procedure: Combined haploidentical and umbilical cord blood allogeneic stem cell transplantation<br>* Patients will receive umbilical cord blood allogeneic stem cell transplantation at the same day as the haploidentical stem cell transplantation. (HLA 6-10/10, TNC≥1-3×10-7/Kg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Defined as the survival duration starting at the day of transplantation, terminating at the day of death or the end of follow-up | 12 months | 
| Disease free survival | Defined as the time starting at the day of transplantation, terminating at the day when the sign of AL is found or the end of follow-up | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative relapse incidence | Defined as the cumulative incidence of relapse after the day of transplantation | 12 months | 
| Cumulative incidence of engraftment | Neutrophil recovery was defined as an absolute neutrophil count(ANC) of 0.5×10^9/L or more for three consecutive days , while platelet recovery difined as 20×10^9/L or more for seven consecutive days without transfusion | 12 months | 
| cumulative incidence of acute graft-versus-host disease(GVHD) | Acute graft versus host disease will be diagnosed and graded by modified Glucksberg criteria | 12 months | 
| cumulative incidence of chronic GVHD at one year | chronic graft versus host disease will be diagnosed and graded by National Institute of Health Consensus (NIH Consensus) | 12 months | 
| Cumulative Incidence of Infectious Complications | Defined as cumulative incidence of viral, fungal and bacterial infections | 12 months | 
| Cumulative Incidence of hemorrhagic cystitis | Defined as the cumulative incidence of hemorrhagic cystitis after the day of transplantation | 12 months | 
| Cumulative Incidence of lymphoproliferative disease | Defined as the cumulative incidence of lymphoproliferative disease after the day of transplantation | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Leukemia, haplo-hematopoietic stem cell transplantation (haplo-HSCT), umbilical cord blood stem cell transplantation (UCBT)