CLAGE Sequential With Flu-Bu Conditioning for Refractory Acute Leukemia

Allogeneic Stem Cell Transplantation Clinical Trial

Official title:

Cladribine With Intermediate Cytarabine, G-CSF and VP16 Sequential With Fludarabine and Busulifan as Condoning Regimen for Refractory Acute Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03882203
• Other study ID #: RJH-Ref-AL-2018
• Status: Completed
• Phase: Phase 2
• Start date: August 1, 2018
• Est. completion date: December 30, 2022

Study information

• Verified date: August 2023
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

For patients with refractory acute leukemia, allogeneic stem cell transplantation is the only curative therapy. Only 20% of patients may achieve long-term survival mostly due to relapse or nor-relapse mortality (NRM). In previous study, we demonstrated that intensive leukemia debulking chemotherapy FLAG-IDA sequential with Flu-BU conditioning is feasible with ~40% long-term survival. In the study, we further modified the chemotherapy with cladribine replacing fludarabine aiming a more potent anti-leukemia effect. Meanwhile, we reduce the dose of busulfan for patients with poor performance status and age over 45 aim to reduce the NRM. All patients will also receive post-transplantation maintenance therapy with low-dose decitabine to prevent relapse.

Description:

For patients with refractory acute leukemia, allogeneic stem cell transplantation is the only curative therapy. Only 20% of patients may achieve long-term survival mostly due to relapse or nor-relapse mortality (NRM). In previous study, we demonstrated that intensive leukemia debulking chemotherapy FLAG-IDA sequential with Flu-BU conditioning is feasible with ~40% long-term survival. The most important cause of treatment failures were relapse and non-relpase mortality. The further analysis demonstrated that patients with higher bone marrow blast before allo-HSCT was associated with treatment failure and patients with poor perforce status or age over 45 had increased rate of NRM. To further optimization the protocol, we modified the chemotherapy with cladribine replacing fludarabine aiming a more potent anti-leukemia effect and replace idarubicin with VP-16. All patients will also receive post-transplantation maintenance therapy with low-dose decitabine (5mg/m2 daily for 5 days) to prevent the further reduce the relapse incidence. We anticipate LFS at 1 year should be above 50% and 1-year LFS of 20% is considered unacceptable.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 30, 2022
• Est. primary completion date: August 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 60 Years

Eligibility

Inclusion Criteria:

• refractory myeloid malignancies including acute myeloid leukemia (AML) or chronic myeloid leukemia in blastic crisis (CML-BC)

• HLA matched sibling,unrelated donor, or haplo-identical donor

• Patients with bone marrow blast >5% and positive measurable disease via flowcytometry or PCR.

Exclusion Criteria:

• patients with active infection

• liver function damage: ALT/AST above 2X normal range; and renal function damage Scr>160µmol/L; insufficient pulmonary function (FEV1,FVC,DLCO<50%)and heart failure or with EF <50%

• mental instability

• unwilling to give inform consent

Related Conditions & MeSH terms

• Allogeneic Stem Cell Transplantation
• Hematologic Neoplasms
• Refractory Hematologic Cancer

Intervention

Drug:
• CLAGE-FluBu
Cladribine combined with cytarabine and VP16 sequential with Fludarabine combined with busulifan

Locations

Country	Name	City	State
China	Blood & Marrow Transplantation Center, RuiJin Hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	leukemia-free survival	From enrollment to any event as relapse or death	1 year
Secondary	overall survival	From enrollment to death	1 year
Secondary	relapse rate	From enrollment to documentation of relapse	1 year
Secondary	non relapse mortality	From enrollment to documentation of death without evidence of leukemia	1 year