Chemotherapy CLAGE-Ven Sequential With Reduced Intensity Conditioning for Refractory Acute Myelodi Leukemia

Refractory Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05870995
• Other study ID #: R/R-AML-2022
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2023
• Est. completion date: September 1, 2026

Study information

• Verified date: November 2023
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: Jiong HU
• Phone: 86-21-64370045
• Email: hj10709[@]rjh.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 1, 2026
• Est. primary completion date: February 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

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%)

Related Conditions & MeSH terms

• Leukemia
• Refractory Leukemia

Intervention

Drug:
• CALGE-VEN- RIC-conditioning
Intensive chemotherapy Cladribine-cytarabine-etoposide -venetoclax sequential with fludarabine, busulfan and melphalan or fludarabine and total marrow irradiation

Locations

Country	Name	City	State
China	Blood & Marrow Transplantation Center, RuiJin Hospital	Shanghai	Shanghai
China	Department of Hematology, Shanghai No 6 Hospital	Shanghai
China	Shanghai ZhaXin 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	disease-free survival (DFS)	patients remain alive in remission without disease progression or relapse	2 year
Secondary	complete remission (CR)	patients achieve clinical remission after transplantation	day 60
Secondary	Overall survival (OS)	patients remain alive	2 year
Secondary	non-relapse mortality (NRM)	patients died without evidence of disease	day 100
Secondary	non-relapse mortality	patients died without evidence of disease	2 year
Secondary	relapse	patients fail to achieve remission or had disease relapse	2 year
Secondary	GRFS	patients remain alive without relapse, without grade III-IV aGVHD and moderate to severe cGVHD	2 year