Clinical trial NCT05870995: Chemotherapy CLAGE-Ven Sequential With Reduced Intensity Conditioning for Refractory Acute Myelodi Leukemia
Official title: A Phase II Single Arm Study of Cladribine, Cytarabine, Etoposide and Venetoclax Sequential With Reduced Dose Conditioning of Fludarabine, Busulfan and Melphalan or Total Marrow Radiation for Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Refractory Leukemia
Keywords: refractory AML, allogeneic stem cell transplantation
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2023-05-23
Enrollment: 100
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The investigators developed a protocol combining chemotherapy of cladribine, cytarabine and etoposide (CLAGE) as debulking treatment sequential with reduced intensity conditioning regimen Flu-Bu to treat patients with refractory acute myeloid leukemia (AML). In this study, the aim is to further evaluate the efficacy and feasibility of the protocol with modifications: 1) reduced dose of CLAGE; 2) Reduced intensity conditioning (RIC) regimen as fludarabine, busulfan and melphalan (MBF) or total marrow irradiation (TMI); 3) Venetoclax was added to the chemotherapy and conditioning regimen.

Detailed description: Refractory AML is associated with poor prognosis. Allogeneic stem cell transplantation is considered as the only curative therapy. Unfortunately, conventional transplantation protocol usually has high relapse rate and high nor-relapse mortality. In previous studies, the investigators established a protocol using intensive chemotherapy (cladribine, cytarabine and etoposide) to reduced the leukemia burden followed by reduced intensity conditioning regimen of Flu-Bu3 with 7 day interval. All patients received maintenance therapy. The 1-year relapse rate was less than 20% but toxicity such as lethal infection was documented in sizable part of patients. In this study, the aim is to further evaluate the efficacy and feasibility of the protocol with following modifications: 1) dose of cytarabine and etoposide are reduced to 1g/m2 and 100mg/m2 daily; 2) conditioning regimen is based on Flu-Bu2 combined with addition of melphalan (100mg/m2) or total marrow irradiation (TMI) in case of contra-indication for busulfan or melphalan; 3) Venetoclax is added to the chemotherapy and conditioning regimen. The modifications intend to reduce both the toxicities and relapse, which may turn into a benefit of disease-free survival (DFS). This is designed as a phase II multi-center prospective study to evaluate the feasibility and efficacy of the protocol.

Eligibility criteria: Inclusion Criteria:

* patients with refractory AML: no remission after 2 induction therapy, relapsed AML within 6 months of 1st CR, relapse AML fail to having CR after reinduction therapy, multiple relapse and refractory relapse AML
* patients with \>5% bone marrow blast by morphology or by LAIP flowcytometry at enrollment
* patients with HLA-matched sibling donor, 9-10/10 matched unrelated donor or haplo-identical family donor
* patients without active infection
* informed consent provided

Exclusion Criteria:

* patients with abnormal liver function (enzyme \>2N or bilirubin \>2N)
* patients with abnormal renal function (Scr \>1.5N)
* patients with poor cardiac function （EF\<45%）

Primary outcomes:
measure: disease-free survival (DFS)
timeFrame: 2 year
Secondary outcomes:
measure: complete remission (CR)
timeFrame: day 60
measure: Overall survival (OS)
timeFrame: 2 year
measure: non-relapse mortality (NRM)
timeFrame: day 100
measure: non-relapse mortality
timeFrame: 2 year
measure: relapse
timeFrame: 2 year
measure: GRFS
timeFrame: 2 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Blood & Marrow Transplantation Center, RuiJin Hospital
state: Shanghai
city: Shanghai
country: China
facility: Department of Hematology, Shanghai No 6 Hospital
city: Shanghai
country: China
facility: Shanghai ZhaXin Hospital
Study officials:
affiliation: Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital
name: Chun Wang
role: STUDY_DIRECTOR
References: