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

November 14, 2023 updated by: Jiong HU, Shanghai Jiao Tong University School of Medicine

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Shanghai, China
      • Shanghai, China
        • Recruiting
        • Department of Hematology, Shanghai No 6 Hospital
        • Contact:
    • Shanghai
      • Shanghai, Shanghai, China, 200025
        • Recruiting
        • Blood & Marrow Transplantation Center, RuiJin Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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%）

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CLAGE-VEN-RIC-Conditioning

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
disease-free survival (DFS)
Time Frame: 2 year
patients remain alive in remission without disease progression or relapse
2 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
non-relapse mortality
Time Frame: 2 year
patients died without evidence of disease
2 year
relapse
Time Frame: 2 year
patients fail to achieve remission or had disease relapse
2 year
GRFS
Time Frame: 2 year
patients remain alive without relapse, without grade III-IV aGVHD and moderate to severe cGVHD
2 year
complete remission (CR)
Time Frame: day 60
patients achieve clinical remission after transplantation
day 60
Overall survival (OS)
Time Frame: 2 year
patients remain alive
2 year
non-relapse mortality (NRM)
Time Frame: day 100
patients died without evidence of disease
day 100

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Jiao Tong University School of Medicine

Investigators

  • Study Director: Chun Wang, Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2023

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

May 13, 2023

First Submitted That Met QC Criteria

May 22, 2023

First Posted (Actual)

May 23, 2023

Study Record Updates

Last Update Posted (Estimated)

November 16, 2023

Last Update Submitted That Met QC Criteria

November 14, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R/R-AML-2022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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