CLAGE Sequential With Flu-Bu Conditioning for Refractory Acute Leukemia

NCT ID: NCT03882203

Last Updated: 2023-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-01
• Study Completion Date: 2022-12-30

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.

Conditions

Refractory Hematologic Cancer; Allogeneic Stem Cell Transplantation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

treatment

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

Group Type: EXPERIMENTAL

CLAGE-FluBu

Intervention Type: DRUG

Cladribine combined with cytarabine and VP16 sequential with Fludarabine combined with busulifan

Interventions

CLAGE-FluBu

Cladribine combined with cytarabine and VP16 sequential with Fludarabine combined with busulifan

Intervention Type: DRUG

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Jiong HU

Head, Blood & Marrow Transplantation program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Junming Li, M.D

Role: STUDY_DIRECTOR

Department of Hematology, Rui Jin Hospital

Locations

Blood & Marrow Transplantation Center, RuiJin Hospital

Shanghai, , China

Countries

China

Other Identifiers

RJH-Ref-AL-2018

Identifier Type: -

Identifier Source: org_study_id