Efficacy and Safety of Cladribine in Combination With CAG in Newly Diagnosed Unfit Patients With AML
Study Details
Study Description
Brief Summary
In this study, the investigators conducted a phase II trial that evaluated the efficacy and safety of cladribine in combination with modified CAG regimen (low-dose cytarabine and aclarubicin) in elderly patients with AML.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
The low-intensity chemotherapy were developed to reduce the early mortality and improve the benefit-risk ratio for longterm survival in elderly or unfit AML patients.Previous studies revealed that the standard dose of CAG regimen consisting of low-dose cytarabine and aclarubicin in combination with granulocyte colonystimulating factor (G-CSF) priming as an induction therapy was well-tolerated by patients and led to a complete remission (CR) rate of 50.0% in patients aged≥ 70 years. Cladribine (2-chlorodeoxyadenosine ) is a nucleoside analogue of anti-adenosine deaminase that has extensive antitumor activity in hematological tumor.The purine analog 2-CdA increases the uptake of Ara-C and the accumulation of its active cytotoxic metabolite 5α-triphosphate Ara-C (Ara-CTP) in leukemia cells. This finding suggests that synergy occurs between cladribine and cytarabine. In this study, the investigators conducted a phase II trial that evaluated the efficacy and safety of cladribine in combination with modified CAG regimen (low-dose cytarabine and aclarubicin) in unfit patients with AML.Patients will receive C-CAG regimen as follows: cladribine 5 mg/m2, d1-5; G-CSF 300 µg, d0-9; aclarubicin 10 mg, d3-6; cytarabine 10mg/ m2 q12h, SC, d3-9; 4 weeks per cycle. The participants are permitted to quit the study if complete remission (CR) was not achieved after two courses of chemotherapy.The participants will be treated for a total of six cycles unless disease progression or unacceptable side effects are observed or participants withdrew their consent.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: C-CAG cladribine 5 mg/m2, d1-5; G-CSF 300 µg, d0-9; aclarubicin 10 mg, d3-6; cytarabine 10mg/ m2 q12h, SC, d3-9; 4 weeks per cycle. |
Drug: Cladribine Injection
Cladribine 5 mg/m2, intravenous drip,d1-5,4 weeks per cycle.
Other Names:
Drug: Aclarubicin
aclarubicin 10 mg, intravenous drip,d3-6,4 weeks per cycle.
Other Names:
Drug: G-CSF
G-CSF 300 µg,subcutaneous injection, d0-9,4 weeks per cycle.
Other Names:
Drug: cytarabine
cytarabine 10mg/ m2, subcutaneous injectionq,q12h, d3-9,4 weeks per cycle.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Cumulative Complete Remission (CR) / CR with incomplete blood count (CRi) rate [At the end of Cycle 2 (each cycle is 28 days)]
Cumulative CR/CRi rate during 2 cycles
Secondary Outcome Measures
- Safety and tolerability of Cladribine in Combination With CAG determined by the type, frequency, severity and relationship of adverse events to study treatment [1 years]
Safety and tolerability of Cladribine in Combination With treatment for CAG for AML (type, frequency, severity and relationship of adverse events to study treatment).
- Event free survival (EFS) [5 years]
The time from registration to induction failure, death or relapse whichever occurs first
- Overall survival (OS) [5 years]
The time from the date of registration to the date of death, whatever the cause. Patients still alive at the date last contact will be censored.
- Prognostic value of MRD [9 months and at relapse]
Assessment of the prognostic value of Minimal Residual Disease (MRD) by flowcytometry or PCR
Eligibility Criteria
Criteria
Inclusion Criteria:
Patients with:
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a diagnosis of AML according to WHO 2016 classification (excluding acute promyelocytic leukemia) including secondary AML (after an antecedent hematological disease (e.g. MDS) and therapy-related AML
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Patients 60 years and older.
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Patients NOT eligible for standard chemotherapy, defined as hematopoietic cell transplantation comorbidity index (HCT-CI) ≥ 3 or Patients NOT eligible for standard chemotherapy for other reasons (wish of patient).
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White blood cell (WBC) ≤ 10 x109/L (prior hydroxyurea allowed for a maximum of 5 days, stop 2 days before start cladribine treatment)
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Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values:
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Serum creatinine ≤ 221.7 µmol/L (≤ 2.5 mg/dL ), unless considered AML-related -Serum bilirubin ≤ 2.5 x upper limit of normal (ULN), unless considered AML-
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related or due to Gilbert's syndrome
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Alanine transaminase (ALT) ≤ 2.5 x ULN, unless considered AML-related
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WHO performance status 0, 1 or 2.
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Patient is willing and able to use adequate contraception during and until 5 months after the last protocol treatment.
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Written informed consent.
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Patient is capable of giving informed consent.
Exclusion Criteria:
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Acute promyelocytic leukemia.
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Acute leukemia's of ambiguous lineage according to WHO 2016
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Patient has symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement)
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Blast crisis of chronic myeloid leukemia.
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Diagnosis of any previous or concomitant malignancy is an exclusion criterion:
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except when the patient completed successfully treatment (chemotherapy and/or surgery and/or radiotherapy) with curative intent for this malignancy at least 6 months prior to randomization. OR
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except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
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Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period ( ≤ 5 days) with Hydroxyurea is allowed
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Current concomitant chemotherapy, radiation therapy, or immunotherapy; other than hydroxyurea
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Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc.)
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Cardiac dysfunction as defined by:
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Myocardial infarction within the last 3 months of study entry, or
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Reduced left ventricular function with an ejection fraction < 40% as measured by MUGA scan or echocardiogram or
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Unstable angina or
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New York Heart Association grade IV congestive heart failure or
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Unstable cardiac arrhythmias.
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History of stroke or intracranial hemorrhage within 6 months prior to randomization.
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Patient has a history of human immunodeficiency virus or active infection with Hepatitis C or B.
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Patients known to be pregnant
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Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance.
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Patients with any serious concomitant medical condition which could, in the opinion of the investigator, compromise participation in the study.
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Patients who have senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
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Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Sun Yat-sen University Cancer Center | Guangzhou | Guangdong | China | 510060 |
Sponsors and Collaborators
- Sun Yat-sen University
Investigators
- Principal Investigator: wang hua, MD., sun yat-sun university cancer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AML-2020