CBA Versus FBA Conditioning Followed by Allogeneic HSCT in Treatment of High Risk and Refractory AML

October 10, 2021 updated by: Chun Wang, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Aim: To evaluated if cladribine based conditioning (CBA) could decrease relapse after HLA matched HSCT in high risk and refractory AML patients as compared with fludarabine based conditioning regimen(FBA).

Study design: open-labed, prospective, multicenter, randomized control study Number of subjects: 60 each group

Treatment:

CBA group: CBA as HSCT conditioning which including cladribine 5mg/m2 day -6 to day -2 , busulfan(iv) 3.2mg/kg day-6 to day -3 and cytarabine 2g/m2 day-6 to day -2.

FBA group: FBA as HSCT conditioning which including fludarabine 30mg/m2 day -6 to day -2, busulfan(iv) 3.2mg/kg day-6 to day -3 and cytarabine 2g/m2 day-6 to day -2.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Relapse is still the main reason of death for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT), especially for those with high risk and refractory disease. Cladribine and fludarabine are both purine analogs used in treatment of AML. Two studies by the Polish Adult Leukemia Group (PALG) demonstrated that the addition of cladribine to DA (DAC) was associated with an increased complete remission (CR) rate and prolonged overall survival (OS) in the general AML population, with the most prominent effect in patients with unfavorable cytogenetics. Therefore we presume cladribine may more effective in eliminating leukemic cells so that reduce relapse after HSCT.

Eligible patients in this study should between 18 to 60 years old with confirmed AML and fulfilled at least one criteria defining high risk or refractory disease.Patients must have HLA 9/10 or 10/10 matched sibling or unrelated donor. Patients will be excluded if they present any contraindication for HSCT, including respiratory failure, heart failure, liver or kidney function failure et al.

To evaluate if cladribine based conditioning (CBA) could decrease relapse after HLA matched HSCT in high risk and refractory AML patients as compared with fludarabine based conditioning regimen(FBA), 120 eligible patients will be randomized to two groups, the CBA group and the FBA group. Patients in the CBA group receive conditioning including cladribine 5mg/m2 day -6 to day -2 , busulfan(iv) 3.2mg/kg day-6 to day -3 and cytarabine 2g/m2 day-6 to day -2. While patients in the FBA group receive conditioning including fludarabine 30mg/m2 day -6 to day -2 , busulfan(iv) 3.2mg/kg day-6 to day -3 and cytarabine 2g/m2 day-6 to day -2. Graft versus host disease(GVHD) prophylactic regimen include cyclosporine A and short term MTX, ATG 6mg/kg is additionally administered to patients with unrelated donors.

Patients will be followed up for 2 years and the primary end point is the cumulative relapse rate at 2 years. The second end points of the study include the overall survival, disease free survival and non-relapse mortality at 2 years.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200080
        • Recruiting
        • Shanghai General Hospital, Shanghai Jiaotong University School of Medicine

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

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of AML confirmed by bone marrow cell morphology, immunology, cytogenetics and molecular biology (MICM). Blast crisis of chronic myeloid leukemia (CML) and AML transferred from myelodysplastic syndrome(MDS) or other diseases are also included.
  2. AML with high risk cytogenetic abnormals, such as FLT3- ITD, et al.
  3. Patients fulfilled at least one of the following criteria defining refractory AML:(1) primary induction failure (PIF) after 2 or more cycles of chemotherapy; (2) first early relapse after a remission duration of fewer than 12 months and refractory to salvage combination chemotherapy; (3) second or subsequent relapse .
  4. Have HLA 9/10 or 10/10 matched siblings or unrelated donor，the donor must match the health conditions of hematopoietic stem cell donation (criteria of China Marrow Donor Program) and be willing to donate.
  5. Performance status score no more than 2 (ECOG criteria).
  6. Adequate organ function as defined by the following criteria:ALT, AST and total serum bilirubin <2×ULN (upper limit of normal), Serum creatinine and BUN <1.25×ULN.
  7. Adequate cardiac function without acute myocardial infarction, arrhythmia or atrioventricular block, heart failure, active rheumatic heart disease and cardiac dilatation.
  8. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
  9. Willingness and ability to comly with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

  1. Presence of any condition inappropriate for HSCT.
  2. Presence of any fatal disease, including respiratory failure, heart failure, liver or kidney function failure et al.
  3. Have no suitable donor.
  4. Pregnancy or breast feeding.
  5. Current treatment on another clinical trail.
  6. Any other condition the investigator judged the patient inappropriate for entry into this study.

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: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: CBA group

CBA as HSCT conditioning:

cladribine 5mg/m2 day -6 to day -2 busulfan(iv) 3.2mg/kg day-6 to day -3 cytarabine 2g/m2 day-6 to day -2
Drug: Cytarabine
Other Names:
  • cytosine arabinoside
Drug: Cladribine
Other Names:
  • chlorodeoxyadenosine
Drug: Busulfan
Other Names:
  • busulphan
ACTIVE_COMPARATOR: FBA group

FBA as HSCT conditioning:

fludarabine 30mg/m2 day -6 to day -2 busulfan(iv) 3.2mg/kg day-6 to day -3 cytarabine 2g/m2 day-6 to day -2
Drug: Fludarabine
Drug: Cytarabine
Other Names:
  • cytosine arabinoside
Drug: Busulfan
Other Names:
  • busulphan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
cumulative relapse rate at 2 year
Time Frame: 2 years
The percentage of all patients who are relapsed within 2 years after allogeneic HSCT.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall survival at 2 year
Time Frame: 2 years
The percentage of all patients who are still alive 2 years after allogeneic HSCT.
2 years
disease free survival at 2year
Time Frame: 2 years
The percentage of all patients who are leukemia free 2 years after allogeneic HSCT.
2 years
non-relapse mortality at 2year
Time Frame: 2 years
The percentage of patients who are dead of all reasons except relapse.
2 years
non-relapse mortality at 100days
Time Frame: 100 days
The percentage of patients who are dead of all reasons except relapse.
100 days

Collaborators and Investigators

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

Sponsor

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Collaborators

Changhai Hospital
Xiangya Hospital of Central South University
Tongji Hospital
Wuhan Union Hospital, China
Fujian Medical University Union Hospital
Tang-Du Hospital
Chengdu PLA General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

August 1, 2016

Primary Completion (ANTICIPATED)

July 31, 2022

Study Completion (ANTICIPATED)

July 31, 2022

Study Registration Dates

First Submitted

November 5, 2017

First Submitted That Met QC Criteria

December 23, 2017

First Posted (ACTUAL)

December 27, 2017

Study Record Updates

Last Update Posted (ACTUAL)

October 12, 2021

Last Update Submitted That Met QC Criteria

October 10, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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