Haploidentical Transplantation in Severe Aplastic Anemia

NCT03246178 | Unknown

• 1 other identifier: 2016QX-KS008
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Severe Aplastic Anemia

Keywords

Haploidentical; Hematopoietic stem cell transplantation; Severe aplastic anemia

Outcome Measures

Primary Outcomes (12)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

MSD-HSCT

OTHER

This group received treatment of matched sibling donor - hematopoietic stem cell transplantation (MSD-HSCT).

Other: MSD-HSCT

HFD-HSCT

EXPERIMENTAL

This group received treatment of haploid family donor - hematopoietic stem cell transplantation (HFD-HSCT).

Other: HFD-HSCT

Interventions

MSD-HSCT OTHER

1. 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; 2. 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; 3. 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.

MSD-HSCT

HFD-HSCT OTHER

1. 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; 2. 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; 3. 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.

HFD-HSCT

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• (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 \[Eastern Cooperative Oncology Group (ECOG) score 0-2\].

You may not qualify if:

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

Sponsors & Collaborators

• Wu Xiaoxiong: lead

Study Sites (1)

Department of Hematology, 304th Clinical Division, Chinese PLA General Hospital

Beijing, 100048, China

Location

MeSH Terms

Conditions

Anemia, Aplastic

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Study Officials

• Xiaoxiong WU, PhD

  The First Affiliated Hospital of General Hospital of PLA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: no masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head, Research group of the Center of Hematology

Model Details: Patients with SAA

Study Record Dates

• First Submitted: May 1, 2017
• First Posted: August 11, 2017
• Study Start: July 10, 2017
• Primary Completion: July 1, 2020
• Study Completion: December 1, 2020
• Last Updated: August 11, 2017

Record last verified: 2017-08

Locations

CN (1)