Efficacy and Safety of Cladribine in Combination With CAG in Newly Diagnosed Unfit Patients With AML

NCT ID: NCT04254640

Last Updated: 2020-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-01

Study Completion Date

2023-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Acute Myeloid Leukemia Elderly Patients Newly Diagnosed

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Cladribine Injection

Intervention Type DRUG

Cladribine 5 mg/m2, intravenous drip,d1-5,4 weeks per cycle.

Aclarubicin

Intervention Type DRUG

aclarubicin 10 mg, intravenous drip,d3-6,4 weeks per cycle.

G-CSF

Intervention Type DRUG

G-CSF 300 µg,subcutaneous injection, d0-9,4 weeks per cycle.

cytarabine

Intervention Type DRUG

cytarabine 10mg/ m2, subcutaneous injectionq,q12h, d3-9,4 weeks per cycle.

Interventions

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Cladribine Injection

Cladribine 5 mg/m2, intravenous drip,d1-5,4 weeks per cycle.

Intervention Type DRUG

Aclarubicin

aclarubicin 10 mg, intravenous drip,d3-6,4 weeks per cycle.

Intervention Type DRUG

G-CSF

G-CSF 300 µg,subcutaneous injection, d0-9,4 weeks per cycle.

Intervention Type DRUG

cytarabine

cytarabine 10mg/ m2, subcutaneous injectionq,q12h, d3-9,4 weeks per cycle.

Intervention Type DRUG

Other Intervention Names

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2-chlorodeoxyadenosine aclarubicin hydrochloride Granulocyte Colony-Stimulating Factor cytarabine hydrochloride

Eligibility Criteria

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Inclusion Criteria

Patients with:

1. 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
2. Patients 60 years and older.
3. 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).
4. White blood cell (WBC) ≤ 10 x109/L (prior hydroxyurea allowed for a maximum of 5 days, stop 2 days before start cladribine treatment)
5. Adequate renal and hepatic functions unless clearly disease related as indicated by the following laboratory values:

* 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-
* related or due to Gilbert's syndrome
* Alanine transaminase (ALT) ≤ 2.5 x ULN, unless considered AML-related
6. WHO performance status 0, 1 or 2.
7. Patient is willing and able to use adequate contraception during and until 5 months after the last protocol treatment.
8. Written informed consent.
9. Patient is capable of giving informed consent.

Exclusion Criteria

1. Acute promyelocytic leukemia.
2. Acute leukemia's of ambiguous lineage according to WHO 2016
3. Patient has symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement)
4. Blast crisis of chronic myeloid leukemia.
5. Diagnosis of any previous or concomitant malignancy is an exclusion criterion:
6. 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
7. except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
8. Patients previously treated for AML (any antileukemic therapy including investigational agents), a short treatment period ( ≤ 5 days) with Hydroxyurea is allowed
9. Current concomitant chemotherapy, radiation therapy, or immunotherapy; other than hydroxyurea
10. Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc.)
11. Cardiac dysfunction as defined by:

* Myocardial infarction within the last 3 months of study entry, or
* Reduced left ventricular function with an ejection fraction \< 40% as measured by MUGA scan or echocardiogram or
* Unstable angina or
* New York Heart Association grade IV congestive heart failure or
* Unstable cardiac arrhythmias.
12. History of stroke or intracranial hemorrhage within 6 months prior to randomization.
13. Patient has a history of human immunodeficiency virus or active infection with Hepatitis C or B.
14. Patients known to be pregnant
15. Patients with a history of non-compliance to medical regimens or who are considered unreliable with respect to compliance.
16. Patients with any serious concomitant medical condition which could, in the opinion of the investigator, compromise participation in the study.
17. Patients who have senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
18. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

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wanghua

Director, Head of hematology, Principal Investigator, Clinical Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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wang hua, MD.

Role: PRINCIPAL_INVESTIGATOR

sun yat-sun university cancer

Locations

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Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status

Countries

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China

Central Contacts

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wang hua, MD.

Role: CONTACT

Phone: 0086-02087342462

Email: [email protected]

Facility Contacts

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hua wang, MD.

Role: primary

Other Identifiers

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AML-2020

Identifier Type: -

Identifier Source: org_study_id