Intensive Chemotherapy UnfitPhase 2CHANCENCT07172204
Alternating Regimen of VA and Low-dose CHA in the Treatment of Unfit Newly Diagnosed AML
A Phase 2 study testing Alternately treated with VA/low CHA regimen in people with Intensive Chemotherapy Unfit and Newly Diagnosed Acute Myeloid Leukemia (AML), run by First Affiliated Hospital of Zhejiang University at 5 sites in China.
Trial summary
This phase II trial tests how well VA alternating with low-dose CHA works in treating unfit patients with newly diagnosed acute myeloid leukemia (AML). This is a prospective, multi-centers, single arm phase II study aimed to overcome VEN resistance and achieve greater MRD negative rate, providing better control of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intensive Chemotherapy Unfit, Newly Diagnosed Acute Myeloid Leukemia (AML), Age ≥60
- What is being tested?
- Alternately treated with VA/low CHA regimen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 5 sitesChina
- Study dates
- 16 Sep 2025to 31 Jul 2029
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Understand the research and sign a written informed consent form;
- Be newly diagnosed with AML according to WHO 2022 criteria without prior treatment;
- or unwilling to undergo IC. Ineligibility for IC is defined as meeting any of the following criteria:
- Age ≥ 60 years
- Age 18-59 years but ineligible for intensive chemotherapy (IC) , meet ≥1 of the following:
- Eastern Cooperative Oncology Group (ECOG) performance status ≥2 at screening;
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- Severe heart failure (congestive heart failure requiring treatment or myocardial infarction history with ejection fraction ≤50%);
- Severe pulmonary dysfunction (DLCO ≤65%, FEV1 ≤65%, dyspnea at rest, or oxygen dependence);
- Severe renal insufficiency requiring dialysis;
- Child-Pugh B or C cirrhosis, or hepatic impairment with total bilirubin >1.5×ULN;
- Mental illness requiring inpatient psychiatric treatment;
- Any comorbidity deemed by physician to contraindicate IC.
Who cannot join
- Diagnosis of: AML arising from chronic myeloid leukemia (CML); myeloid sarcoma; acute promyelocytic leukemia (APL) or presence of FLT3-ITD mutations;
- Active malignancies (except adequately treated carcinoma in situ or basal cell carcinoma) within 2 years prior to Cycle 1 Day 1 (C1D1);
- Major surgery or systemic anticancer therapy within 28 days before C1D1;
- Known hypersensitivity to: Active pharmaceutical ingredients: cladribine, homoharringtonine, cytarabine, venetoclax, azacitidine; Any excipients in study drug formulations;
- GI conditions impairing oral drug absorption: Dysphagia; short-gut syndrome; gastroparesis or related disorders;
- Uncontrolled active infection;
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- Controlled infection permitted if: Afebrile (<38°C) and hemodynamically stable (SBP >90 mmHg, HR <100 bpm) for ≥72 hours pre-C1D1; on non-interacting antimicrobial regimen; active HBV/HCV infection (Chronic carriers require PI approval with viral load monitoring); HIV-positive patients receiving HAART;
- Pregnancy/lactation or refusal of contraception: Negative serum β-hCG within 24h pre-C1D1;
- Psychiatric disorders or social circumstances compromising protocol compliance;
- Prior AML-directed therapy except: cytoreduction for hyperleukocytosis per institutional guidelines (hydroxyurea, leukapheresis); supportive growth factors;
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
China5 sites, 5 recruiting
- Recruiting
Beijing Chao-Yang Hospital, Capital Medical University
Beijing, Beijing Municipality
Honghu Zhu, 86+010-85230000, zhuhhdoc@163.com
- Recruiting
Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang
Jie Sun, 8615305714109, jsun1492@zju.edu.cn
- Recruiting
the Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi
Li Yu, 86+0791-86120120, zengyulii@126.com
- Recruiting
Shenzhen University General Hospital
Shenzhen, Guangdong
Lixin Wang, 86+13718000488
- Recruiting
the First Affiliated Hospital of Soochow University
Suzhou, Jiangsu
Suning Chen, 86+13656205608, chensuning@suda.edu.cn
About this study
Official title: The Efficacy and Safety of VA Alternating With Low-dose CHA in the Treatment of Newly Diagnosed Unfit AML: a Prospective, Multi-centers, Single Arm Phase II Study
This phase II trial tests how well VA alternating with low-dose CHA works in treating unfit patients with newly diagnosed acute myeloid leukemia (AML). This is a prospective, multi-centers, single arm phase II study aimed to overcome VEN resistance and achieve greater MRD negative rate, providing better control of treatment for unfit AML.
Read the detailed description
This clinical study protocol investigates a novel treatment for newly diagnosed Acute Myeloid Leukemia (AML) patients ineligible to receive intensive chemotherapy (IC). Eligibility is defined as age ≥60 or age 18-59 with significant comorbidities. Key exclusions include specific AML subtypes including Acute promyelocytic leukemia (APL); FLT3-ITD mutations and active infections. The Intervention is a two-phase regimen. The Induction Phase consists of four alternating 28-day cycles of Venetoclax + Azacitidine (VA) and low-dose Cladribine + Homoharringtonine + Cytarabine (CHA). This is followed by a Maintenance Phase of 24 cycles of VA therapy. The Primary Endpoint is the rate of Minimal Residual Disease (MRD) negativity after two alternating cycles. Secondary Endpoints include composite complete remission rate, overall survival, and incidence of treatment-emergent adverse events. Clear Withdrawal Criteria are defined for situations involving unacceptable toxicity, lack of therapeutic benefit, or patient/investigator decision.
- Being tested
- Alternately treated with VA/low CHA regimen
- Keywords
- Acute Myeloid Leukemia, Venetoclax, alternating, Homoharringtonine, Cladribine, age 60 and older, intensive chemotherapy unfit, newly diagnosed
- 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.
Alternately treated with VA/low CHA regimenDrug
- Induction Phase (4 alternating cycles): Participants will receive 4 cycles of alternating therapy:
- VA Cycle:
- Venetoclax 400 mg PO daily on Days 1-28
- Azacitidine 75 mg/m² SC daily on Days 1-7
- Low-dose CHA Cycle:
- Cladribine 5 mg/m² IV daily on Days 1-3
- Homoharringtonine 1 mg/m² IV daily on Days 1-5
- Cytarabine 20 mg SC every 12 hours on Days 1-10 Alternating sequence: VA → CHA → VA → CHA → VA → CHA → VA → CHA
- Maintenance Phase (24 months):
Following induction, participants will receive:
- Venetoclax 400 mg PO daily on Days 1-28
- Azacitidine 75 mg/m² SC daily on Days 1-7 Repeated every 28 days for 24 cycles.
We aimed to compare this clinical intervention with standard VA which is:
- Venetoclax 400 mg PO daily on Days 1-28
- Azacitidine 75 mg/m² SC daily on Days 1-7 Repeated every 28 days for at least 24 cycles.
| Study group | Role | What they receive |
|---|---|---|
| VA alternating with low-CHA | Experimental | single treatment arm Receives: Drug: Alternately treated with VA/low CHA regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Negative rate of minimal residual lesions (MRD)
Proportion of patients achieving MRD-negative status (≤0.1% leukemic blasts by flow cytometry) after two cycles of alternating VA/CHA therapy
Measured: At day28 of the second alternating (one alternating is VA plus low-CHA)
Secondary outcomes (7)
composite complete remission, CRc
Proportion achieving CR or CRi per ELN 2022 criteria at each cycle completion
Measured: At day28 of the first alternating and the second alternating (one alternating is VA plus low-CHA)
Overall response rate, ORR
Proportion achieving PR or better (CR/CRh/CRi/MLFS/PR) per IWG criteria at each cycle completion
Measured: At day28 of the first alternating and the second alternating (one alternating is VA plus low-CHA)
Overall Survival, OS
Time from enrollment to death from any cause, whichever came first (censored at last follow-up for survivors)
Measured: Time from enrollment to death from any cause, whichever came first, assessed up to 24 months
disease-free survival, DFS
Time from first response to relapse or death (censored at last disease assessment)
Measured: From the date of first response until the date of relapse or death from any cause, whichever came first, assessed up to 24 months
MRD negative DFS, DFS-MRD
Time from first MRD-negative status to MRD-positive (confirmed by a second check within 2 weeks).
Measured: From the date of first MRD-negative status until the date of MRD-positive, relapse or death due to relapse, whichever came first, assessed up to 24months.
Event-free survival, EFS
Time from enrollment to treatment failure (not achieved PR after the first alternating, or not achieved CR after 2 alternatings, or continuous MRD positive after 4 alternatings), relapse, or death. （one alternating is VA plus low-CHA)
Measured: from enrollment until the date of treatment failure, relapse or death from any cause, whichever came first, assessed up to 24 months
Incidence of adverse events (AEs)
Incidence of CTCAE v6.0-graded AEs from day 1 of treatment to study completion
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2025
- Study start16 Sep 2025
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intensive Chemotherapy UnfitStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital of Zhejiang 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Zhejiang University
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie
- Responsible party
- Principal investigator, Jie Sun, First Affiliated Hospital of Zhejiang University
- Investigators
- Jie Dr. Sun, M.D, Ph.D, Principal investigator, Bone Marrow Transplantation Center of The First Affiliated Hospital, Zhejiang University School of MedicineShanshan Prof. Pei, Ph.D, Study director, Liangzhu Laboratory, Zhejiang University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07172204
- Sponsor's protocol ID
- IIT20250072C
- Acronym
- CHANCE
- Status last verified
- Nov 2025
- First submitted
- 19 Aug 2025
- Last updated
- 4 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement.
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of VA Alternating With Low-dose CHA in the Treatment of Newly Diagnosed Unfit AML: a Prospective, Multi-centers, Single Arm Phase II Study
- ClinicalTrials.gov ID
- NCT07172204
- Acronym / sponsor ID
- CHANCE / IIT20250072C
- Keywords
- Acute Myeloid Leukemia, Venetoclax, alternating, Homoharringtonine, Cladribine, age 60 and older, intensive chemotherapy unfit, newly diagnosed
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Zhejiang UniversityUniversity, hospital or other
- Collaborators
- AbbVie
- Study start
- 16 Sep 2025 (actual)
- Primary completion
- 31 Jul 2027 (estimated)
- Study completion
- 31 Jul 2029 (estimated)
- First posted
- 15 Sep 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 phase II trial tests how well VA alternating with low-dose CHA works in treating unfit patients with newly diagnosed acute myeloid leukemia (AML). This is a prospective, multi-centers, single arm phase II study aimed to overcome VEN resistance and achieve greater MRD negative rate, providing better control of treatment for unfit AML.
Detailed description
This clinical study protocol investigates a novel treatment for newly diagnosed Acute Myeloid Leukemia (AML) patients ineligible to receive intensive chemotherapy (IC). Eligibility is defined as age ≥60 or age 18-59 with significant comorbidities. Key exclusions include specific AML subtypes including Acute promyelocytic leukemia (APL); FLT3-ITD mutations and active infections. The Intervention is a two-phase regimen. The Induction Phase consists of four alternating 28-day cycles of Venetoclax + Azacitidine (VA) and low-dose Cladribine + Homoharringtonine + Cytarabine (CHA). This is followed by a Maintenance Phase of 24 cycles of VA therapy. The Primary Endpoint is the rate of Minimal Residual Disease (MRD) negativity after two alternating cycles. Secondary Endpoints include composite complete remission rate, overall survival, and incidence of treatment-emergent adverse events. Clear Withdrawal Criteria are defined for situations involving unacceptable toxicity, lack of therapeutic benefit, or patient/investigator decision.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VA alternating with low-CHA | Experimental | Drug: Alternately treated with VA/low CHA regimensingle treatment arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Understand the research and sign a written informed consent form;
- Be newly diagnosed with AML according to WHO 2022 criteria without prior treatment;
- or unwilling to undergo IC. Ineligibility for IC is defined as meeting any of the following criteria:
- Age ≥ 60 years
- Age 18-59 years but ineligible for intensive chemotherapy (IC) , meet ≥1 of the following:
Key exclusion criteria (10 listed)
- Diagnosis of: AML arising from chronic myeloid leukemia (CML); myeloid sarcoma; acute promyelocytic leukemia (APL) or presence of FLT3-ITD mutations;
- Active malignancies (except adequately treated carcinoma in situ or basal cell carcinoma) within 2 years prior to Cycle 1 Day 1 (C1D1);
- Major surgery or systemic anticancer therapy within 28 days before C1D1;
- Known hypersensitivity to: Active pharmaceutical ingredients: cladribine, homoharringtonine, cytarabine, venetoclax, azacitidine; Any excipients in study drug formulations;
- GI conditions impairing oral drug absorption: Dysphagia; short-gut syndrome; gastroparesis or related disorders;
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 |
|---|---|---|
| Alternately treated with VA/low CHA regimen1. Induction Phase (4 alternating cycles): Participants will receive 4 cycles of alternating therapy: * VA Cycle: * Venetoclax 400 mg PO daily on Days 1-28 * Azacitidine 75 mg/m² SC daily on Days 1-7 * Low-dose CHA Cycle: * Cladribine 5 mg/m² IV daily on Days 1-3 * Homoharringtonine 1 mg/m² IV daily on Days 1-5 * Cytarabine 20 mg SC every 12 hours on Days 1-10 Alternating sequence: VA → CHA → VA → CHA → VA → CHA → VA → CHA 2. Maintenance Phase (24 months): Following induction, participants will receive: * Venetoclax 400 mg PO daily on Days 1-28 * Azacitidine 75 mg/m² SC daily on Days 1-7 Repeated every 28 days for 24 cycles. We aimed to compare this clinical intervention with standard VA which is: * Venetoclax 400 mg PO daily on Days 1-28 * Azacitidine 75 mg/m² SC daily on Days 1-7 Repeated every 28 days for at least 24 cycles. | Drug | VA alternating with low-CHA |
Primary outcome
Negative rate of minimal residual lesions (MRD)
Time frame: At day28 of the second alternating (one alternating is VA plus low-CHA)
Proportion of patients achieving MRD-negative status (≤0.1% leukemic blasts by flow cytometry) after two cycles of alternating VA/CHA therapy
7 secondary outcomes
composite complete remission, CRc
Time frame: At day28 of the first alternating and the second alternating (one alternating is VA plus low-CHA)
Overall response rate, ORR
Time frame: At day28 of the first alternating and the second alternating (one alternating is VA plus low-CHA)
Overall Survival, OS
Time frame: Time from enrollment to death from any cause, whichever came first, assessed up to 24 months
disease-free survival, DFS
Time frame: From the date of first response until the date of relapse or death from any cause, whichever came first, assessed up to 24 months
MRD negative DFS, DFS-MRD
Time frame: From the date of first MRD-negative status until the date of MRD-positive, relapse or death due to relapse, whichever came first, assessed up to 24months.
Event-free survival, EFS
Time frame: from enrollment until the date of treatment failure, relapse or death from any cause, whichever came first, assessed up to 24 months
Incidence of adverse events (AEs)
Time frame: up to 3 years
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 4 Feb 2026.
- Individual participant dataSharing planned: Yes. Deidentified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement.
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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.
Jie Dr. Sun, M.D, Ph.D principal investigator
Bone Marrow Transplantation Center of The First Affiliated Hospital, Zhejiang University School of Medicine
Shanshan Prof. Pei, Ph.D study director
Liangzhu Laboratory, Zhejiang University School of Medicine
5 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 Alternately treated with VA/low CHA regimen in people with Intensive Chemotherapy Unfit and Newly Diagnosed Acute Myeloid Leukemia (AML), run by First Affiliated Hospital of Zhejiang University at 5 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 12 inclusion and 10 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 4 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 Jie Sun (+8615305714109, jsun1492@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Negative rate of minimal residual lesions (MRD) (time frame: At day28 of the second alternating (one alternating is VA plus low-CHA)). 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 4 Feb 2026.