Relapsed/Refractory AMLPhase 4NCT06763666
CLAG+VEN vs CLAG in the Treatment of Relapsed/Refractory AML
A Phase 4 study testing Cladribine, Cytarabine and G-CSF in people with Relapsed/Refractory AML, run by Nanfang Hospital, Southern Medical University at 1 site in China.
Trial summary
This is a multicenter, prospective, randomized controlled clinical study comparing the efficacy and safety of CLAG+VEN and CLAG regimens in relapsed/refractory(r/r) AML. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Relapsed/Refractory AML
- What is being tested?
- Cladribine, Cytarabine and G-CSF
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 172 participants
- Where
- 1 siteChina
- Study dates
- Feb 2025to Dec 2025
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed of AML according to the World Health Organization (WHO) classification.
- All patients should aged 18 to 65 years.
- Diagnosed of relapsed and refractory AML, according to The guidelines for diagnosis and treatment of relapse /refractory acute myelogenous leukemia in China（2023）
- Diagnostic criteria for relapsed AML: Leukemia cells reappear in the peripheral blood or primitive cells in the bone marrow ≥ 5% (excluding other reasons such as bone marrow regeneration after consolidation chemotherapy) after CR, or leukemia cell infiltration appears outside the marrow.
- Diagnostic criteria for refractory AML: The newly diagnosed patients who failed to respond to two courses of standard treatment; Patients who relapsed within 12 months after consolidation intensive therapy; Patients who relapsed after 12 months and failed to respond to conventional chemotherapy; Patients with two or more recurrences; Patients with persistent extramedullary leukemia.
- The score of Eastern Cooperative Oncology Group (ECOG) is 0-2.
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- Renal function: creatinine clearance rate ≥ 30ml/min.
- Liver function: ALT<5 times normal value, bilirubin<3 times normal value.
- Predicted survival ≥ 3 months.
- Able to accept oral Venetoclax.
- Sign an informed consent form and be able to understand and follow the procedures required by this protocol.
Who cannot join
- Diagnosed of acute promyelocytic leukemia (AML-M3)
- Patients with central nervous system (CNS) invasion.
- Cardiac function < grade 2.
- Known human immunodeficiency virus (HIV) infection.
- Other clinically significant uncontrolled conditions, including but not limited to: a. uncontrolled or active systemic infections (viruses, bacteria, or fungi); b. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment; c. Secondary tumors requiring active treatment.
- Allergy to experimental drugs.
- Pregnant and lactating women.
- Patients who ineligible for the study according to the investigator's assessment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Guopan Yu contact
China1 site
Department of Hematology,Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, 510515
Guopan Yu, +8615876559968, yugpp@163.com
About this study
Official title: A Multicenter, Prospective, Randomized Controlled Study Comparing the Efficacy and Safety of CLAG(Cladribine, Cytarabine and G-CSF) Combined With Venetoclax and CLAG in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
This is a multicenter, prospective, randomized controlled clinical study comparing the efficacy and safety of CLAG+VEN and CLAG regimens in relapsed/refractory(r/r) AML.
Read the detailed description
The efficacy and prognosis of relapsed/refractory(r/r) AML are very poor, and there is no standard chemotherapy regimen were defined for r/r AML. Cladribine, a purine analogue, exerts cytotoxic, proapoptotic, and antiproliferative effects on AML cells. Previous studies have confirmed the efficacy of cladribine in the treatment of r/r AML, with a response rate of 30-45%.Our previous experience has shown that CLAG in combination of venetoclax are effective with tolerable toxicity profiling. However, there is a lack of multicenter, prospective, randomized controlled trials to further confirm the results. Therefore, a clinical study is planned to evaluate the efficacy and safety of CLAG+VEN compared to CLAG in r/r AML who were eligible for intensive therapy.
- Conditions
- Relapsed/Refractory AML
- Being tested
- Cladribine, Cytarabine, G-CSF, Venetoclax
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CladribineDrug
Also called 2-CdA, CdA
Given IV
CytarabineDrug
Also called Ara-C
Given IV
G-CSFDrug
Also called Filgrastim, Granulocyte Colony-stimulating Factor
Given SC
VenetoclaxDrug
Also called Venclexta
Given PO
| Study group | Role | What they receive |
|---|---|---|
| CLAGV regimen | Experimental | CLAG combined with venetoclax for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF and venetoclax.
Venetoclax is administered orally at 400mg/d on days 2-8. When combination with P450 3A4 inhibitor, VEN should be reduced to 100-200mg/d and monitoring of VEN blood concentrations is recommended at qualified centers. Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined. Receives: Drug: Cladribine; Drug: Cytarabine; Drug: G-CSF; Drug: Venetoclax |
| CLAG regimen | Active comparator | CLAG regimen for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF.
Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined. Receives: Drug: Cladribine; Drug: Cytarabine; Drug: G-CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Complete remission (cCR, CR+CRi)
Will compare composite complete remission(CR+CRi: complete response [CR] and complete response with incomplete blood count recovery [CRi]) between CLAGV regimen and CLAG regimen
Measured: At the end of Cycle 1 (each cycle is 28 days)
Secondary outcomes (7)
Overall Response rate (ORR)
Will compare ORR(completed remission[CR], completed remission with incomplete blood count recovery[CRi], and partial remission[PR]) rates between the study arms
Measured: At the end of Cycle 1 (each cycle is 28 days)
MRDneg CR rate
Will compare MRD-negative cCR rates between the study arms
Measured: At the end of Cycle 1 (each cycle is 28 days)
Overall Survival(OS)
Will compare OS between the study arms
Measured: 1 year post treatment
Relapse free survival(RFS)
Will compare RFS between the study arms
Measured: 1 year post treatment
Duration of completed response(DoR)
Will compare DoR between the study arms
Measured: 1 year post treatment
Relapse rate
Will compare relapse rate between the study arms
Measured: 1 year post treatment
Incidence of Adverse Events
Will use the CTCAE (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events) version 5.0 for toxicity and adverse event reporting. Will describe the incidence of infection and treatment-related adverse events.
Measured: Duration of treatment, up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2025
- Study startFeb 2025 (estimated)
- Primary completionJun 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory AMLStudies of the same condition, open and under way.
- More trials run by Nanfang Hospital, Southern Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 172 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou No.12 People's Hospital, Guangzhou Panyu Central Hospital, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou First People's Hospital, Foresea Life Insurance Guangzhou General Hospital, Guangdong Second Provincial General Hospital, Jiangmen Central Hospital, Shantou Central Hospital, Maoming People's Hospital, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Dongguan People's Hospital, Tungwah Hospital of Sun Yat-Sen University, Shenzhen Hospital of Southern Medical University, Central People's Hospital of Zhanjiang, ZhuHai Hospital, Shenzhen Second People's Hospital, Zhongshan People's Hospital, Guangdong, China, LiuZhou People's Hospital, First People's Hospital of Foshan, Southern Medical University, China, Affiliated Hospital of Guangdong Medical University, Guilin Medical University, China, Yuebei People's Hospital, Huizhou Municipal Central Hospital, Second Affiliated Hospital of Guangzhou Medical University, Peking University Shenzhen Hospital
- Responsible party
- Sponsor
- Investigators
- Guopan Yu, Principal investigator, Nanfang Hospital, Southern Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06763666
- Sponsor's protocol ID
- NFEC-2024-639
- Status last verified
- Jan 2025
- First submitted
- 30 Dec 2024
- Last updated
- 8 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Prospective, Randomized Controlled Study Comparing the Efficacy and Safety of CLAG(Cladribine, Cytarabine and G-CSF) Combined With Venetoclax and CLAG in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT06763666
- Acronym / sponsor ID
- NFEC-2024-639
- Conditions
- Relapsed/Refractory AML
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 172 participants (estimated)
- Lead sponsor
- Nanfang Hospital, Southern Medical UniversityUniversity, hospital or other
- Collaborators
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou No.12 People's Hospital, Guangzhou Panyu Central Hospital, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou First People's Hospital, Foresea Life Insurance Guangzhou General Hospital, Guangdong Second Provincial General Hospital, Jiangmen Central Hospital, Shantou Central Hospital, Maoming People's Hospital, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Dongguan People's Hospital, Tungwah Hospital of Sun Yat-Sen University, Shenzhen Hospital of Southern Medical University, Central People's Hospital of Zhanjiang, ZhuHai Hospital, Shenzhen Second People's Hospital, Zhongshan People's Hospital, Guangdong, China, LiuZhou People's Hospital, First People's Hospital of Foshan, Southern Medical University, China, Affiliated Hospital of Guangdong Medical University, Guilin Medical University, China, Yuebei People's Hospital, Huizhou Municipal Central Hospital, Second Affiliated Hospital of Guangzhou Medical University, Peking University Shenzhen Hospital
- Study start
- Feb 2025 (estimated)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 8 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, prospective, randomized controlled clinical study comparing the efficacy and safety of CLAG+VEN and CLAG regimens in relapsed/refractory(r/r) AML.
Detailed description
The efficacy and prognosis of relapsed/refractory(r/r) AML are very poor, and there is no standard chemotherapy regimen were defined for r/r AML. Cladribine, a purine analogue, exerts cytotoxic, proapoptotic, and antiproliferative effects on AML cells. Previous studies have confirmed the efficacy of cladribine in the treatment of r/r AML, with a response rate of 30-45%.Our previous experience has shown that CLAG in combination of venetoclax are effective with tolerable toxicity profiling. However, there is a lack of multicenter, prospective, randomized controlled trials to further confirm the results. Therefore, a clinical study is planned to evaluate the efficacy and safety of CLAG+VEN compared to CLAG in r/r AML who were eligible for intensive therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CLAGV regimen | Experimental | Drug: Cladribine, Drug: Cytarabine, Drug: G-CSF, Drug: VenetoclaxCLAG combined with venetoclax for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF and venetoclax. Venetoclax is administered orally at 400mg/d on days 2-8. When combination with P450 3A4 inhibitor, VEN should be reduced to 100-200mg/d and monitoring of VEN blood concentrations is recommended at qualified centers. Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined. |
| CLAG regimen | Active comparator | Drug: Cladribine, Drug: Cytarabine, Drug: G-CSFCLAG regimen for relapsed/refractory AML. Patients were randomized and those entering the experimental group received cladribine, cytarabine, G-CSF. Cladribine is administered intravenously at a dose of 5 mg/m2/d on days 1-5. Cytarabine is administered intravenously at a dose of 1g/m2/d on days 1-5, starting 2h after cladribine and maintained for more than 3h. The dose of G-CSF was 5ug/kg/d subcutaneously injected on days 0-5. Generally, starting 12 hours before the start of chemotherapy, if the absolute value of white blood cell count is ≥ 20×10^9/L, the use is suspended.For patients with FLT3 mutations, corresponding inhibitors such as sorafenib and gilteritinib can be combined. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Diagnosed of AML according to the World Health Organization (WHO) classification.
- All patients should aged 18 to 65 years.
- Diagnosed of relapsed and refractory AML, according to The guidelines for diagnosis and treatment of relapse /refractory acute myelogenous leukemia in China（2023）
- Diagnostic criteria for relapsed AML: Leukemia cells reappear in the peripheral blood or primitive cells in the bone marrow ≥ 5% (excluding other reasons such as bone marrow regeneration after consolidation chemotherapy) after CR, or leukemia cell infiltration appears outside the marrow.
- Diagnostic criteria for refractory AML: The newly diagnosed patients who failed to respond to two courses of standard treatment; Patients who relapsed within 12 months after consolidation intensive therapy; Patients who relapsed after 12 months and failed to respond to conventional chemotherapy; Patients with two or more recurrences; Patients with persistent extramedullary leukemia.
Key exclusion criteria (8 listed)
- Diagnosed of acute promyelocytic leukemia (AML-M3)
- Patients with central nervous system (CNS) invasion.
- Cardiac function < grade 2.
- Known human immunodeficiency virus (HIV) infection.
- Other clinically significant uncontrolled conditions, including but not limited to: a. uncontrolled or active systemic infections (viruses, bacteria, or fungi); b. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment; c. Secondary tumors requiring active treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CladribineAlso: 2-CdA, CdAGiven IV | Drug | CLAG regimen, CLAGV regimen |
| CytarabineAlso: Ara-CGiven IV | Drug | CLAG regimen, CLAGV regimen |
| G-CSFAlso: Filgrastim, Granulocyte Colony-stimulating FactorGiven SC | Drug | CLAG regimen, CLAGV regimen |
| VenetoclaxAlso: VenclextaGiven PO | Drug | CLAGV regimen |
Primary outcome
Composite Complete remission (cCR, CR+CRi)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Will compare composite complete remission(CR+CRi: complete response [CR] and complete response with incomplete blood count recovery [CRi]) between CLAGV regimen and CLAG regimen
7 secondary outcomes
Overall Response rate (ORR)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
MRDneg CR rate
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Overall Survival(OS)
Time frame: 1 year post treatment
Relapse free survival(RFS)
Time frame: 1 year post treatment
Duration of completed response(DoR)
Time frame: 1 year post treatment
Relapse rate
Time frame: 1 year post treatment
Incidence of Adverse Events
Time frame: Duration of treatment, up to 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Guopan Yu contact
Guopan Yu principal investigator
Nanfang Hospital, Southern Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Cladribine, Cytarabine and G-CSF in people with Relapsed/Refractory AML, run by Nanfang Hospital, Southern Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 8 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Guopan Yu (+8615876559968, yugpp@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Complete remission (cCR, CR+CRi) (time frame: At the end of Cycle 1 (each cycle is 28 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2025.