Clinical trial NCT03882203: CLAGE Sequential With Flu-Bu Conditioning for Refractory Acute Leukemia
Official title: Cladribine With Intermediate Cytarabine, G-CSF and VP16 Sequential With Fludarabine and Busulifan as Condoning Regimen for Refractory Acute Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Refractory Hematologic Cancer
Allogeneic Stem Cell Transplantation
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2019-03-20
Enrollment: 18
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: leukemia-free survival
timeFrame: 1 year
Secondary outcomes:
measure: overall survival
timeFrame: 1 year
measure: relapse rate
timeFrame: 1 year
measure: non relapse mortality
timeFrame: 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Blood & Marrow Transplantation Center, RuiJin Hospital
Study officials:
affiliation: Department of Hematology, Rui Jin Hospital
name: Junming Li, M.D
role: STUDY_DIRECTOR
References: