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

Sponsor

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (Other)

Overall Status

Recruiting

CT.gov ID

NCT03384225

Collaborator

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

120

Enrollment

Location

Arms

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Aim: To evaluated if cladribine based conditioning (CBA) could decrease relapse after haploidentical allogeneic 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.

Condition or Disease	Intervention/Treatment	Phase
High Risk Acute Myeloid Leukemia Allogeneic Hematopoeitic Stem Cell Transplantation	Drug: Cladribine Drug: Fludarabine Drug: Busulfan Drug: Cytarabine	Phase 3

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. Haploidentical HSCT was the main option for those without HLA matched donors and the number of haploidentical transplants has covered over fifty percent of all allogeneic transplants in China. We designed this study to evaluated if cladribine based conditioning (CBA) could decrease relapse after haploidentical HSCT in high risk and refractory AML patients as compared with fludarabine based conditioning regimen(FBA).

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 have no HLA matched sibling or unrelated donors but have haploidentical 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 CBA could decrease relapse after haploidentical HSCT in high risk and refractory AML patients as compared with 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 ATG 2.5mg/kg d-4 to d-1, cyclosporine A and short term MTX.

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 Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel Assignment open labled randomized controlled studyParallel Assignment open labled randomized controlled study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 1, 2016

Anticipated Primary Completion Date :

Jul 31, 2022

Anticipated Study Completion Date :

Jul 31, 2022

Arms and Interventions

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: Cladribine Other Names: chlorodeoxyadenosine Drug: Busulfan Other Names: busulphan Drug: Cytarabine Other Names: cytosine arabinoside
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: Busulfan Other Names: busulphan Drug: Cytarabine Other Names: cytosine arabinoside

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: Cladribine

Other Names:

chlorodeoxyadenosine

Drug: Busulfan

Other Names:

busulphan

Drug: Cytarabine

Other Names:

cytosine arabinoside

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: Busulfan

Other Names:

busulphan

Drug: Cytarabine

Other Names:

cytosine arabinoside

Outcome Measures

Primary Outcome Measures

cumulative relapse rate at 2 year [2 years]
The percentage of all patients who are relapsed within 2 years after allogeneic HSCT.

Secondary Outcome Measures

overall survival at 2 year [2 years]
The percentage of all patients who are still alive 2 years after allogeneic HSCT.
disease free survival at 2year [2 years]
The percentage of all patients who are leukemia free 2 years after allogeneic HSCT.
non-relapse mortality at 2year [2 years]
The percentage of patients who are dead within 2 years of all reasons except relapse.
non-relapse mortality at 100days [100 days]
The percentage of patients who are dead within 100days of all reasons except relapse.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
AML with high risk cytogenetic abnormals, such as FLT3- ITD, et al.
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 .
Have no HLA matched siblings or unrelated donors, but have haploidentical donor. The donor must match the health conditions of hematopoietic stem cell donation (criteria of China Marrow Donor Program) and be willing to donate.
Performance status score no more than 2 (ECOG criteria).
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.
Adequate cardiac function without acute myocardial infarction, arrhythmia or atrioventricular block, heart failure, active rheumatic heart disease and cardiac dilatation.
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.
Willingness and ability to comly with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

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