CLAGE Sequential With Flu-Bu Conditioning for Refractory Acute Leukemia

Phase 2

Completed

• Conditions: Refractory Hematologic Cancer; Allogeneic Stem Cell Transplantation
• Interventions: Drug: CLAGE-FluBu

• Registration Number: NCT03882203
• Lead Sponsor: Shanghai Jiao Tong University School of Medicine

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2018-08-01
• Study First Submitted: 2019-03-18
• Study First Submitted QC: 2019-03-18
• Study First Posted: 2019-03-20
• Primary Completion: 2021-08-30
• Study Completion: 2022-12-30
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-14
• Last Update Posted: 2023-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treatment	CLAGE-FluBu	Patients receive the study protocol: CLAGE sequential with Flu-Bu as conditioning regimen followed by low-dose decitabine maintenance

Primary Outcome Measures

Name	Time	Method
leukemia-free survival	1 year	From enrollment to any event as relapse or death

Secondary Outcome Measures

Name	Time	Method
overall survival	1 year	From enrollment to death
relapse rate	1 year	From enrollment to documentation of relapse
non relapse mortality	1 year	From enrollment to documentation of death without evidence of leukemia

Trial Locations

Locations (1)

Blood & Marrow Transplantation Center, RuiJin Hospital; 🇨🇳 Shanghai, China