Haploidentical Transplantation in Severe Aplastic Anemia

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages Any age
• All sexes
• No healthy volunteers
• Child, Adult, Older adult

Trial locations and contacts

1 site in 1 country.

About this study

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

Conditions

Severe Aplastic Anemia

Being tested

MSD-HSCT, HFD-HSCT

Keywords

Haploidentical, Hematopoietic stem cell transplantation, Severe aplastic anemia

Medical subject headings

Anemia, Aplastic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• MSD-HSCTOther

  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.

• HFD-HSCTOther

  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.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. 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).

   Measured: In the first months after infusion

2. 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.

   Measured: TRT was defined as toxic effects occurring within 40 days after HSCT

3. 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.

   Measured: Days +30 after HSCT

4. 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.

   Measured: Days +100 after HSCT

5. 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.

   Measured: Days +180 after HSCT

6. 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.

   Measured: Days +365 after HSCT

7. OS 1-year

   OS was defined as the time from transplantation to death from any cause or the last follow-up.

   Measured: 1-year after HSCT

8. OS 2-year

   OS was defined as the time from transplantation to death from any cause or the last follow-up.

   Measured: 2-year after HSCT

9. OS 5-year

   OS was defined as the time from transplantation to death from any cause or the last follow-up.

   Measured: 5-year after HSCT

10. 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.

    Measured: 1-year after HSCT

11. EFS 2-year

    EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.

    Measured: 2-year after HSCT

12. EFS 5-year

    EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure.

    Measured: 5-year after HSCT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted11 Aug 2017
2. Study start10 Jul 2017
3. Primary completion1 Jul 2020 (estimated)
4. Study completion1 Dec 2020 (estimated)

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Other trials for Severe Aplastic AnemiaStudies of the same condition, open and under way.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.