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CLAGE-VEN Sequential With Reduced Dose MBF for Refractory AML

Sponsor
Shanghai Jiao Tong University School of Medicine (Other)
Overall Status
Recruiting
CT.gov ID
NCT05870995
Collaborator
(none)
30
Enrollment
3
Locations
1
Arm
43
Anticipated Duration (Months)
10
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

We 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 AML. In this study, we further evaluate the protocol with modifications: 1) reduced dose of CLAGE; 2) RIC conditioning regimen as Flu-Bu-Mel; 3) Venetoclax was added to the chemotherapy and conditioning regimen.

Condition or Disease Intervention/Treatment Phase
  • Drug: CALGE-VEN- RIC-MBF
 Phase 2

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 our previous studies, we 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, we further evaluate 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); 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 Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Single Arm Study of CLAGE-VEN Chemotherapy Sequential With Reduced Dose MBF Conditioning Regimen for Patients With Refractory Acute Myeloid Leukemia
Actual Study Start Date :
Feb 1, 2023
Anticipated Primary Completion Date :
Feb 1, 2026
Anticipated Study Completion Date :
Sep 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: CLAGE-VEN-RIC-MBF

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 PBSC: day 0

Drug: CALGE-VEN- RIC-MBF
Intensive chemotherapy Cladribine-cytarabine-etoposide -venetoclax sequential with fludarabine, busulfan and melphalan

Outcome Measures

Primary Outcome Measures

  1. disease-free survival [2 year]

    patients remain alive in remission without disease progression or relapse

Secondary Outcome Measures

  1. complete remission [day 60]

    patients achieve clinical remission after transplantation

  2. Over all survival [2 year]

    patients remain alive

  3. non-relapse mortality [day 100]

    patients died without evidence of disease

  4. non-relapse mortality [2 year]

    patients died without evidence of disease

  5. relapse [2 year]

    patients fail to achieve remission or had disease relapse

  6. GRFS [2 year]

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

Eligibility Criteria

Criteria

Ages Eligible for Study:
16 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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%）

Contacts and Locations

Locations

Site City State Country Postal Code
1 Blood & Marrow Transplantation Center, RuiJin Hospital Shanghai Shanghai China 200025
2 Department of Hematology, Shanghai No 6 Hospital Shanghai China
3 Shanghai ZhaXin Hospital Shanghai China

Sponsors and Collaborators

  • Shanghai Jiao Tong University School of Medicine

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Jiong HU, Head, Blood & Marrow Transplantation Center, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier:
NCT05870995
Other Study ID Numbers:
  • R/R-AML-2022
First Posted:
May 23, 2023
Last Update Posted:
May 23, 2023
Last Verified:
May 1, 2023
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Jiong HU, Head, Blood & Marrow Transplantation Center, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine
refractory AML, allogeneic stem cell transplantation
Additional relevant MeSH terms:
Leukemia

Study Results

No Results Posted as of May 23, 2023