Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Etoposide

Cytarabine

Venetoclax

Fludarabine

Fludarabine phosphate

Melphalan

Etoposide phosphate

Busulfan

Cladribine

Cladribine: 5mg/m2 day -21 to d -17 cytarabine: 1g/m2 day -21- to d -17 etoposide: 100mg/m2 day -17 to -15 venetoclax: 100mg day-21; 200mg day -20, 400mg day -19 to day-3 Fludarabine: 30mg/m2 day -7 to -3 Busulfan: 3.2mg/kg day -6 to -5 Melphalan: 50mg/m2 day -4 to -3. or Fludarabine 30mg/m2 day -7 to -3 Total marrow irradiation day-5 to -3 PBSC: day 0

Conditioning regimen cane delayed to in patients with ongoing active infection or work-up of donors after CLAGE-VEN chemotherapy based on clinicians' decision. Patients receiving all-HSCT in cytopenia are classified as sequential while patients with recovered CBC are considered as bridging transplantation.

Intensive chemotherapy Cladribine-cytarabine-etoposide -venetoclax sequential with fludarabine, busulfan and melphalan or fludarabine and total marrow irradiation

CALGE-VEN- RIC-conditioning

Jiong HU

Jieling Jiang

Jiong HU, M.D.,

Ling Wang, M.D.,

Chunkang Chang

Chun Wang

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.

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.

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

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

IPD data is available only based on request to PI and study director

patients remain alive in remission without disease progression or relapse

patients achieve clinical remission after transplantation

patients died without evidence of disease

patients fail to achieve remission or had disease relapse

patients remain alive without relapse, without grade III-IV aGVHD and moderate to severe cGVHD

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Chemotherapy CLAGE-Ven Sequential With Reduced Intensity Conditioning for Refractory Acute Myelodi Leukemia	NCT05870995	Refractory Leuk...	CALGE-VEN- RIC-...	16 Years - 65 Years	Shanghai Jiao Tong University School of Medicine
Chemotherapy CLAGE-Ven Sequential With Reduced Intensity Conditioning for Refractory Acute Myelodi Leukemia	NCT05870995	Refractory Leuk...	CALGE-VEN- RIC-...	16 Years - 65 Years	Shanghai Jiao Tong University School of Medicine

Spots Global Cancer Trial Database for refractory aml, allogeneic stem cell transplantation