Haploidentical Transplantation in Severe Aplastic Anemia

Severe Aplastic Anemia Clinical Trial

Official title:

A Research on Haploidentical Transplantation in Severe Aplastic Anemia Using Reduced-intensity Fludarabine-based Conditioning

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03246178
• Other study ID #: 2016QX-KS008
• Status: Enrolling by invitation
• Phase: N/A
• First received: May 1, 2017
• Last updated: August 8, 2017
• Start date: July 10, 2017
• Est. completion date: December 1, 2020

Study information

• Verified date: August 2017
• Source: Chinese PLA General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective case-control study on SAA patients treated with HSCT, order to further discuss and assess the safety, feasibility and effectiveness of HFD-HSCT which performed with reduced-intensity fludarabine-based conditioning regimen.Our findings would indicate that SAA patients who lack MSD benefited most if HFD-HSCT was performed with reduced-intensity fludarabine-based conditioning regimen, and our improved outcomes with HFD-HSCT may lead to a salvaged therapy and an expanded direct role for SAA in the future.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 60
• Est. completion date: December 1, 2020
• Est. primary completion date: July 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

(i) Diagnosis of SAA, very SAA or SAA and paroxysmal nocturnal hemoglobinuria (PNH) according to the International Aplastic Anemia Study Group; (ii) SAA patients no response to previous IST; (iii) adequate performance status [Eastern Cooperative Oncology Group (ECOG) score 0-2].

Exclusion Criteria:

(i) Congenital forms of aplastic anemia; (ii)Patients with any severe pulmonary, cardiac, liver, or renal diseases or active infection.

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Severe Aplastic Anemia

Intervention

Other:
• MSD-HSCT
Conditioning regimens: (A) Patients had SAA and PNH, or heavy transfusion (RBC=25U), or failed rabbit ATG therapy, and received 0.8 mg/kg/6h busulfan (days -7 to -6), 30mg/m2/day fludarabine (days -5 to -2), 25 mg/kg/day cyclophosphamide (days -5 to -2) and 2.5 mg/kg/day r-ATG (days -5 to -2). (B) The other patients with SAA or VSAA received same procedure but without busulfan; Allogeneic HSC infusion: Doner BM cells were harvested to achieve a target mononuclear cell count (MNC) of 2-4 × 108 per kilogram of recipient weight. The target MNC from PB was 4-6× 108 per kilogram of recipient weight; Prophylaxis and treatment of GVHD: GVHD prophylaxis consisted of intravenous CSP 2-3 mg/kg/day in divided doses beginning on the day before transplantation (day -5) and the target concentration was adjusted to 150-250 ng/ml. The oral MMF dose was 20 mg/kg/day from day -1 and was tapered off after 1 months if no aGVHD was observed.
• HFD-HSCT
Conditioning regimens: (A) Patients had SAA and PNH, or heavy transfusion (RBC=25U), or failed rabbit ATG therapy, and received 0.8 mg/kg/6h busulfan (days -7 to -6), 35mg/m2/day fludarabine (days -5 to -2), 25 mg/kg/day cyclophosphamide (days -5 to -2) and 2.5 mg/kg/day r-ATG (days -5 to -2). (B) The other patients with SAA or VSAA received same procedure but without busulfan; Allogeneic HSC infusion: Doner BM cells were harvested to achieve a target mononuclear cell count (MNC) of 2-4 × 108 per kilogram of recipient weight. The target MNC from PB was 4-6× 108 per kilogram of recipient weight; Prophylaxis and treatment of GVHD: GVHD prophylaxis consisted of intravenous CSP 2-3 mg/kg/day in divided doses beginning on the day before transplantation (day -5) and the target concentration was adjusted to 200-300 ng/ml. The oral MMF dose was 20 mg/kg/day from day -3 and was tapered off after 2 months if no aGVHD was observed.

Locations

Country	Name	City	State
China	Department of Hematology, 304th Clinical Division, Chinese PLA General Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Wu Xiaoxiong

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Engraftment	Neutrophil engraftment was defined as the first of three consecutive days in which the neutrophil counts (ANC) exceeded 0.50 × 109/L, and platelet engraftment was defined as the first of five consecutive days in which the platelet count exceeded 20 × 109/L without transfusion. GF was classified as follows: (1) primary non-engraftment (failure to reach a neutrophil count of 0.5×109/L after transplant); (2) rejection (decrease in blood counts to < 0.5×109/L neutrophils, after achieving a neutrophil count of 0.5×109/L); (3) late graft failure (decrease of blood counts after day 100 to < 1.0×109/L neutrophils and < 30×109/L platelets).	In the first months after infusion
Primary	Toxicity grading	The transplantation-related toxicity (TRT) was graded using the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0. Organ damage due to GVHD or infectious complications were excluded.	TRT was defined as toxic effects occurring within 40 days after HSCT
Primary	Chimerism analyses +30	Chimerism would be evaluated in recipient BM cells usually on days +30 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors.	Days +30 after HSCT
Primary	Chimerism analyses +100	Chimerism would be evaluated in recipient BM cells usually on days +180 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors.	Days +100 after HSCT
Primary	Chimerism analyses +180	Chimerism would be evaluated in recipient BM cells usually on days +100 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors.	Days +180 after HSCT
Primary	Chimerism analyses +365	Chimerism would be evaluated in recipient BM cells usually on days +365 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors.	Days +365 after HSCT
Primary	OS 1-year	OS was defined as the time from transplantation to death from any cause or the last follow-up.	1-year after HSCT
Primary	OS 2-year	OS was defined as the time from transplantation to death from any cause or the last follow-up.	2-year after HSCT
Primary	OS 5-year	OS was defined as the time from transplantation to death from any cause or the last follow-up.	5-year after HSCT
Primary	EFS 1-year	EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.; EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.	1-year after HSCT
Primary	EFS 2-year	EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.	2-year after HSCT
Primary	EFS 5-year	EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.	5-year after HSCT