Refractory LeukemiaPhase 2NCT05870995
Chemotherapy CLAGE-Ven Sequential With Reduced Intensity Conditioning for Refractory Acute Myelodi Leukemia
A Phase 2 study testing CALGE-VEN- RIC-conditioning in people with Refractory Leukemia, run by Shanghai Jiao Tong University School of Medicine at 3 sites in China.
Trial summary
The investigators developed a protocol combining chemotherapy of cladribine, cytarabine and etoposide (CLAGE) as debulking treatment sequential with reduced intensity conditioning regimen Flu-Bu to treat patients with refractory acute myeloid leukemia (AML). Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Refractory Leukemia
- What is being tested?
- CALGE-VEN- RIC-conditioning
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 3 sitesChina
- Study dates
- 1 Feb 2023to 1 Sep 2026
- Phase
- Phase 2
- 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 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- patients with refractory AML: no remission after 2 induction therapy, relapsed AML within 6 months of 1st CR, relapse AML fail to having CR after reinduction therapy, multiple relapse and refractory relapse AML
- patients with >5% bone marrow blast by morphology or by LAIP flowcytometry at enrollment
- patients with HLA-matched sibling donor, 9-10/10 matched unrelated donor or haplo-identical family donor
- patients without active infection
- informed consent provided
Who cannot join
- patients with abnormal liver function (enzyme >2N or bilirubin >2N)
- patients with abnormal renal function (Scr >1.5N)
- patients with poor cardiac function （EF<45%）
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites, 3 recruiting
- Recruiting
Blood & Marrow Transplantation Center, RuiJin Hospital
Shanghai, Shanghai Municipality, 200025
Jiong HU, M.D.,, 86-21-64370045, hj10709@rjh.com.cn
Ling Wang, M.D.,, 86-21-64370045, cclingjar@163.com
- Recruiting
Department of Hematology, Shanghai No 6 Hospital
Shanghai
Chunkang Chang, 86-21-64369181, changchunkang@sjtu.edu.cn
- Recruiting
Shanghai ZhaXin Hospital
Shanghai
Chun Wang, 13386259777, wangc@gobroadhealthcare.com
About this study
Official title: A Phase II Single Arm Study of Cladribine, Cytarabine, Etoposide and Venetoclax Sequential With Reduced Dose Conditioning of Fludarabine, Busulfan and Melphalan or Total Marrow Radiation for Refractory Acute Myeloid Leukemia
The investigators developed a protocol combining chemotherapy of cladribine, cytarabine and etoposide (CLAGE) as debulking treatment sequential with reduced intensity conditioning regimen Flu-Bu to treat patients with refractory acute myeloid leukemia (AML). In this study, the aim is to further evaluate the efficacy and feasibility of the protocol with modifications: 1) reduced dose of CLAGE; 2) Reduced intensity conditioning (RIC) regimen as fludarabine, busulfan and melphalan (MBF) or total marrow irradiation (TMI); 3) Venetoclax was added to the chemotherapy and conditioning regimen.
Read the detailed description
Refractory AML is associated with poor prognosis. Allogeneic stem cell transplantation is considered as the only curative therapy. Unfortunately, conventional transplantation protocol usually has high relapse rate and high nor-relapse mortality. In previous studies, the investigators established a protocol using intensive chemotherapy (cladribine, cytarabine and etoposide) to reduced the leukemia burden followed by reduced intensity conditioning regimen of Flu-Bu3 with 7 day interval. All patients received maintenance therapy. The 1-year relapse rate was less than 20% but toxicity such as lethal infection was documented in sizable part of patients. In this study, the aim is to further evaluate the efficacy and feasibility of the protocol with following modifications: 1) dose of cytarabine and etoposide are reduced to 1g/m2 and 100mg/m2 daily; 2) conditioning regimen is based on Flu-Bu2 combined with addition of melphalan (100mg/m2) or total marrow irradiation (TMI) in case of contra-indication for busulfan or melphalan; 3) Venetoclax is added to the chemotherapy and conditioning regimen. The modifications intend to reduce both the toxicities and relapse, which may turn into a benefit of disease-free survival (DFS). This is designed as a phase II multi-center prospective study to evaluate the feasibility and efficacy of the protocol.
- Conditions
- Refractory Leukemia
- Being tested
- CALGE-VEN- RIC-conditioning
- Keywords
- refractory AML, allogeneic stem cell transplantation
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CALGE-VEN- RIC-conditioningDrug
Intensive chemotherapy Cladribine-cytarabine-etoposide -venetoclax sequential with fludarabine, busulfan and melphalan or fludarabine and total marrow irradiation
| Study group | Role | What they receive |
|---|---|---|
| CLAGE-VEN-RIC-Conditioning | Experimental | Cladribine: 5mg/m2 day -21 to d -17 cytarabine: 1g/m2 day -21- to d -17 etoposide: 100mg/m2 day -17 to -15 venetoclax: 100mg day-21; 200mg day -20, 400mg day -19 to day-3 Fludarabine: 30mg/m2 day -7 to -3 Busulfan: 3.2mg/kg day -6 to -5 Melphalan: 50mg/m2 day -4 to -3. or Fludarabine 30mg/m2 day -7 to -3 Total marrow irradiation day-5 to -3 PBSC: day 0
Conditioning regimen cane delayed to in patients with ongoing active infection or work-up of donors after CLAGE-VEN chemotherapy based on clinicians' decision. Patients receiving all-HSCT in cytopenia are classified as sequential while patients with recovered CBC are considered as bridging transplantation. Receives: Drug: CALGE-VEN- RIC-conditioning |
What is being measured
The primary outcome is the main question the study is designed to answer.
disease-free survival (DFS)
patients remain alive in remission without disease progression or relapse
Measured: 2 year
Secondary outcomes (6)
complete remission (CR)
patients achieve clinical remission after transplantation
Measured: day 60
Overall survival (OS)
patients remain alive
Measured: 2 year
non-relapse mortality (NRM)
patients died without evidence of disease
Measured: day 100
non-relapse mortality
patients died without evidence of disease
Measured: 2 year
relapse
patients fail to achieve remission or had disease relapse
Measured: 2 year
GRFS
patients remain alive without relapse, without grade III-IV aGVHD and moderate to severe cGVHD
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2023
- Study start1 Feb 2023
- Primary completion1 Feb 2026 (estimated)
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory LeukemiaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Jiao Tong University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jiong HU, Shanghai Jiao Tong University School of Medicine
- Investigators
- Chun Wang, Study director, Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05870995
- Sponsor's protocol ID
- R/R-AML-2022
- Status last verified
- Feb 2025
- First submitted
- 13 May 2023
- Last updated
- 18 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD data is available only based on request to PI and study director
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Single Arm Study of Cladribine, Cytarabine, Etoposide and Venetoclax Sequential With Reduced Dose Conditioning of Fludarabine, Busulfan and Melphalan or Total Marrow Radiation for Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT05870995
- Acronym / sponsor ID
- R/R-AML-2022
- Conditions
- Refractory Leukemia
- Keywords
- refractory AML, allogeneic stem cell transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Study start
- 1 Feb 2023 (actual)
- Primary completion
- 1 Feb 2026 (estimated)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 23 May 2023 (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.
The investigators developed a protocol combining chemotherapy of cladribine, cytarabine and etoposide (CLAGE) as debulking treatment sequential with reduced intensity conditioning regimen Flu-Bu to treat patients with refractory acute myeloid leukemia (AML). In this study, the aim is to further evaluate the efficacy and feasibility of the protocol with modifications: 1) reduced dose of CLAGE; 2) Reduced intensity conditioning (RIC) regimen as fludarabine, busulfan and melphalan (MBF) or total marrow irradiation (TMI); 3) Venetoclax was added to the chemotherapy and conditioning regimen.
Detailed description
Refractory AML is associated with poor prognosis. Allogeneic stem cell transplantation is considered as the only curative therapy. Unfortunately, conventional transplantation protocol usually has high relapse rate and high nor-relapse mortality. In previous studies, the investigators established a protocol using intensive chemotherapy (cladribine, cytarabine and etoposide) to reduced the leukemia burden followed by reduced intensity conditioning regimen of Flu-Bu3 with 7 day interval. All patients received maintenance therapy. The 1-year relapse rate was less than 20% but toxicity such as lethal infection was documented in sizable part of patients. In this study, the aim is to further evaluate the efficacy and feasibility of the protocol with following modifications: 1) dose of cytarabine and etoposide are reduced to 1g/m2 and 100mg/m2 daily; 2) conditioning regimen is based on Flu-Bu2 combined with addition of melphalan (100mg/m2) or total marrow irradiation (TMI) in case of contra-indication for busulfan or melphalan; 3) Venetoclax is added to the chemotherapy and conditioning regimen. The modifications intend to reduce both the toxicities and relapse, which may turn into a benefit of disease-free survival (DFS). This is designed as a phase II multi-center prospective study to evaluate the feasibility and efficacy of the protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CLAGE-VEN-RIC-Conditioning | Experimental | Drug: CALGE-VEN- RIC-conditioningCladribine: 5mg/m2 day -21 to d -17 cytarabine: 1g/m2 day -21- to d -17 etoposide: 100mg/m2 day -17 to -15 venetoclax: 100mg day-21; 200mg day -20, 400mg day -19 to day-3 Fludarabine: 30mg/m2 day -7 to -3 Busulfan: 3.2mg/kg day -6 to -5 Melphalan: 50mg/m2 day -4 to -3. or Fludarabine 30mg/m2 day -7 to -3 Total marrow irradiation day-5 to -3 PBSC: day 0 Conditioning regimen cane delayed to in patients with ongoing active infection or work-up of donors after CLAGE-VEN chemotherapy based on clinicians' decision. Patients receiving all-HSCT in cytopenia are classified as sequential while patients with recovered CBC are considered as bridging transplantation. |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- patients with refractory AML: no remission after 2 induction therapy, relapsed AML within 6 months of 1st CR, relapse AML fail to having CR after reinduction therapy, multiple relapse and refractory relapse AML
- patients with >5% bone marrow blast by morphology or by LAIP flowcytometry at enrollment
- patients with HLA-matched sibling donor, 9-10/10 matched unrelated donor or haplo-identical family donor
- patients without active infection
- informed consent provided
Key exclusion criteria (3 listed)
- patients with abnormal liver function (enzyme >2N or bilirubin >2N)
- patients with abnormal renal function (Scr >1.5N)
- patients with poor cardiac function （EF<45%）
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 |
|---|---|---|
| CALGE-VEN- RIC-conditioningIntensive chemotherapy Cladribine-cytarabine-etoposide -venetoclax sequential with fludarabine, busulfan and melphalan or fludarabine and total marrow irradiation | Drug | CLAGE-VEN-RIC-Conditioning |
Primary outcome
disease-free survival (DFS)
Time frame: 2 year
patients remain alive in remission without disease progression or relapse
6 secondary outcomes
complete remission (CR)
Time frame: day 60
Overall survival (OS)
Time frame: 2 year
non-relapse mortality (NRM)
Time frame: day 100
non-relapse mortality
Time frame: 2 year
relapse
Time frame: 2 year
GRFS
Time frame: 2 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 18 Feb 2025.
- Individual participant dataSharing planned: No. IPD data is available only based on request to PI and study director
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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.
Chun Wang study director
Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CALGE-VEN- RIC-conditioning in people with Refractory Leukemia, run by Shanghai Jiao Tong University School of Medicine at 3 sites 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 5 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 18 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Jiong HU (86-21-64370045 ext. 601878, hj10709@rjh.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
disease-free survival (DFS) (time frame: 2 year). 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 18 Feb 2025.