LeukemiaNCT06643962
Venetoclax Combined with Intensive Therapy for Acute Myeloid Leukemia Patients with Lower Early Peripheral Blast Clearance Rate After Standard Induction Therapy
A study testing Venetoclax, Idarubincin and Cytarabine in people with Leukemia and Leukemia, Myeloid, run by Affiliated Hospital of Nantong University at 1 site in China.
Trial summary
This single-center prospective cohort study aims to evaluate the efficacy and safety of Intensifying treatment with Venetoclax along with intensive chemotherapy in patients with newly diagnosed acute myeloid leukemia (AML) except acute promyelocytic leukemia (non-APL) and exhibiting lower early peripheral blast… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute
- What is being tested?
- Venetoclax, Idarubincin and Cytarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 1 siteChina
- Study dates
- 31 Oct 2024to 31 Oct 2027
- Phase
- Interventional
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed AML, except for the APL subtype, according to the 2022 World Health Organization classification (WHO 2022 criteria)
- Age ≥18 years and ≤70 years
- Eligible for intensive chemotherapy
- No prior chemotherapy for AML except hydroxyurea for up to 14 days during the diagnostic screening phase for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell [WBC] counts>25x10^9/L)
- Eastern Cooperative Oncology Group (ECOG) performance status≤2
- Adequate renal function is defined as:
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- Serum creatinine≤2.0×upper limit of normal (ULN)
- Creatinine clearance (CrCl)>30 mL/min calculated by the Cockcroft-Gault equation.
- Adequate hepatic and heart function is defined as:
- Serum total bilirubin≤1.5×ULN unless considered due to Gilbert's disease, or leukemic involvement
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)≤2.5×ULN, unless considered due to leukemic involvement
- Myocardial enzyme<2.0×ULN
- Left ventricular ejection fraction is within the normal range by measure of echocardiogram (ECHO)
- Signed a written informed consent form (ICF)
- Female participants who are of non-reproductive potential (i.e., post-menopausal by history of no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female participants of childbearing potential must have a negative serum pregnancy test upon study entry
Who cannot join
- AML with BCR-ABL1 or myeloid blast crisis of CML
- Participants who have received prior treatment for AML with chemotherapy, hypomethylating agents, or venetoclax
- Participants who are ineligible for intensive induction chemotherapy:
- ≧71 years old OR
- ≧18 to 70 years old and fulfill at least one criterion associated with lack of fitness for intensive induction chemotherapy:
- ECOG PS of 2-3
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- Cardiac history of CHF requiring treatment or Ejection Fraction ≦50% or chronic stable angina
- Diffusing capacity of the lungs for carbon monoxide (DLCO)≦65% or the forced expiratory volume in one second (FEVI) ≦65%
- Participants with a prior history of MDS, MPN, or MDS/MPN
- Participants with other concurrent malignant tumors on treatment, except for:
- Malignancy treated with curative intent and with no known active disease present for ≧3 years
- Adequately treated non-melanoma skin cancer or lentigo maligna without current evidence of disease
- Adequately treated carcinoma in situ without current evidence of disease
- Localized prostate cancer with a Gleason score of 6 or less
- Pregnant or lactating women
- Active heart disease is defined as any one of the following:
- Uncontrolled or symptomatic angina pectoris
- A myocardial infarction six months before enrolled
- Arrhythmia needs medication or with severe clinical symptoms
- Uncontrolled or symptomatic congestive heart failure (New York Hear Association [NYHA] classification> grade 2)
- Participants with an active, uncontrolled, systemic fungal, bacterial, or viral infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment
- Participants with an active viral infection caused by HIV, hepatitis B, or hepatitis C virus that cannot be controlled by treatment
- Participants with evidence of central nervous system leukemia before the study treatment
- Participants with epilepsy which needs drug treatment, dementia, or other abnormal mental states that prevent understanding or following the protocol
- Conditions that restrict the intake or absorption of orally administered drugs
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Affiliated hospital of Nantong University
Nantong, Jiangsu, 226001
Sun Yingxin, Dr, +86-13646249970, syx20194132088@163.com
Yingxin Sun, Dr
About this study
Official title: A Single-Center Prospective Cohort Study to Evaluate the Efficacy and Safety of Intensifying Treatment with Venetoclax in Patients with Newly Diagnosed Acute Myeloid Leukemia (non-APL) and Exhibiting Lower Early Peripheral Blast Clearance Rate After Standard Intensive Induction Chemotherapy
This single-center prospective cohort study aims to evaluate the efficacy and safety of Intensifying treatment with Venetoclax along with intensive chemotherapy in patients with newly diagnosed acute myeloid leukemia (AML) except acute promyelocytic leukemia (non-APL) and exhibiting lower early peripheral blast clearance rate (EPBCR) after standard Intensive Induction therapy (3+7 regimen).
Read the detailed description
This is a single-center, prospective cohort study for the intensifying treatment with venetoclax on the standard 3+7 regimen in newly diagnosed AML (non-APL) participants who have lower EPBCR based on ≦1.5log on day 4 of the 3+7 regimen.
The key eligible criteria are newly diagnosed and treatment-naïve AML (non-APL) according to the WHO 2022 criteria. Participants are between 18 and 70 years old and fit for intensive chemotherapy. A leukemia-associated immunophenotype (LAIP) defined by multiparameter flow cytometry (MFC) according to the 2022 ELN recommendation (2022 ELN) is necessary for enrollment in this trial.
All eligible participants receive the 3+7 regimen. Pretreatment with hydroxyurea is permitted to manage leukocytosis.
LAIP+ cells are enumerated on EDTA-anticoagulated peripheral blood collected before chemotherapy on days 1 and 4 of the first induction cycle (each cycle is 28 days). At least 100 circulating LAIP+ cells per microliter on day 1 are required as inclusion criteria to ensure optimal sensitivity. The EPBCR is calculated on day 4 of the first induction regimen as a ratio converted to a logarithmic scale between the absolute peripheral blood LAIP+ cell count on day 1 (baseline) and day 4. A cut-off of 1.5 log is decisional to assign participants to treatment modalities. Participants with EPBCR>1.5 log (EPBCRhigh) complete the 3+7 regimen and are managed according to standard clinical practice. Participants with EPBCR≦1.5 log (EPBCRlow) receive intensified treatment with venetoclax orally along with the standard 3+7 regimen on days 5-14. A venetoclax dose ramp-up schedule is required in the first induction therapy.
After two cycles of induction therapy, participants who fail to achieve composite complete remission (CR/CRi, CRc) may receive an alternative regimen per their physicians' decision.
After CR/CRi is achieved, participants proceed with consolidation therapy or allo-HSCT based on their 2022 ELN risk categories. Participants with favorable risk should go through four cycles (each cycle is 28 days) of consolidation therapy, those with adverse risk should go through allogeneic hematopoietic stem cell transplantation (allo-HSCT) after two cycles of consolidation therapy, and those with intermediate risk can receive allo-HSCT after two cycles of consolidation therapy if suitable donors are available or continue with four cycles of consolidation therapy. Participants receive four cycles of consolidation regimen of intermediate-dose cytarabine for age >60 years old or high-dose cytarabine for age >60 years old. The consolidation therapy will be combined with venetoclax in the EPBCRlow cohort and not in the EPBCRhigh cohort.
After consolidation, participants will receive maintenance therapy per their physicians' decision and be observed.
- Conditions
- Leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute
- Being tested
- Venetoclax, Idarubincin, Cytarabine
- Keywords
- acute myeloid leukemia, venetoclax, intensive chemotherapy, early peripheral blast clearance, newly diagnosed
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
Also called Bcl-2 inhibitors
Venetoclax in the EPBCRlow cohort will be added to the ongoing 3+7 regimen. In the first induction cycle: venetoclax needs to be ramped up: 100 mg on day 5, 200mg on day 6, and 400mg on days 7-14, orally once daily. In the second induction (if required), venetoclax 400mg will be administered orally once daily on days 5-14 without a dose ramp-up schedule. Venetoclax in the EPBCRlow cohort during consolidation therapy: 400mg on days 1-7, orally once daily, along with the consolidation chemotherapy.
IdarubincinDrug
Also called IDA
Idarubicin (IDA): 10mg/m^2/d (age <60 years old) or 6mg/m^2/d on days 1-3, intravenously (IV).
CytarabineDrug
Also called Ara-C
During induction therapy: 100mg/m2/d on days 1-7, IV. During consolidation therapy: intermediate-dose cytarabine for age >55 years old: 1.0g/m^2 q12h on days 1-3, high-dose cytarabine for age ≦55 years old: 2g/m2 q12h on days 1-3.
| Study group | Role | What they receive |
|---|---|---|
| Assigned interventions | Experimental | Participants with EPBCR>1.5 log (EPBCRhigh) complete the 3+7 regimen and are managed according to standard clinical practice. Participants with EPBCR≦1.5 log (EPBCRlow) receive intensified treatment with venetoclax orally along with the standard 3+7 regimen on days 5-14. A venetoclax dose ramp-up schedule is required in the first induction therapy. Receives: Drug: Venetoclax; Drug: Idarubincin; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
CRc rate after one cycle of induction therapy
The proportion of participants achieving CR/CRi by the initiation of next cycle of therapy (each cycle is 28 days).
Measured: Up to one month
Secondary outcomes (5)
CRc rate after two cycle of induction therapy
The cumulative proportion of participants achieving CR/CRi after two cycles of induction therapy and before starting the next cycle of therapy.
Measured: Up to 2 months
CRMRD-Rate
The cumulative proportion of participants achieving CR/CRi without measurable residual disease after two cycles of induction therapy and before starting the next cycle of therapy.
Measured: Up to 2 months
Event-free survival (EFS)
The time from enrollment to treatment failure is defined as failure to achieve CR, CRi, or PR after two cycles of induction therapy, death from any cause, or relapse after achieving CR/CRi, whichever occurs first. If no specified events occur at the date of the last disease assessment, participants will be censored.
Measured: Up to 12 months
Relapse free survival (RFS)
From the date of achieving CR/CRi until the date of documented relapse or death due to any cause or the last follow-up day. If no specified events occur at the date of the last disease assessment, participants will be censored.
Measured: Up to 24 months
Overall survival Overall survival (OS)
The time from enrollment to death due to any cause. If death does not occur at the date of the last disease assessment, participants will be censored.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2024
- Study start31 Oct 2024
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Affiliated Hospital of Nantong 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 83 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Affiliated Hospital of Nantong University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06643962
- Sponsor's protocol ID
- TF-IIT-2024-01
- Status last verified
- Oct 2024
- First submitted
- 14 Oct 2024
- Last updated
- 12 Nov 2024
- 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 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Center Prospective Cohort Study to Evaluate the Efficacy and Safety of Intensifying Treatment with Venetoclax in Patients with Newly Diagnosed Acute Myeloid Leukemia (non-APL) and Exhibiting Lower Early Peripheral Blast Clearance Rate After Standard Intensive Induction Chemotherapy
- ClinicalTrials.gov ID
- NCT06643962
- Acronym / sponsor ID
- TF-IIT-2024-01
- Conditions
- Leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute
- Keywords
- acute myeloid leukemia, venetoclax, intensive chemotherapy, early peripheral blast clearance, newly diagnosed
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 83 participants (estimated)
- Lead sponsor
- Affiliated Hospital of Nantong UniversityUniversity, hospital or other
- Study start
- 31 Oct 2024 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Oct 2027 (estimated)
- First posted
- 16 Oct 2024 (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 single-center prospective cohort study aims to evaluate the efficacy and safety of Intensifying treatment with Venetoclax along with intensive chemotherapy in patients with newly diagnosed acute myeloid leukemia (AML) except acute promyelocytic leukemia (non-APL) and exhibiting lower early peripheral blast clearance rate (EPBCR) after standard Intensive Induction therapy (3+7 regimen).
Detailed description
This is a single-center, prospective cohort study for the intensifying treatment with venetoclax on the standard 3+7 regimen in newly diagnosed AML (non-APL) participants who have lower EPBCR based on ≦1.5log on day 4 of the 3+7 regimen.
The key eligible criteria are newly diagnosed and treatment-naïve AML (non-APL) according to the WHO 2022 criteria. Participants are between 18 and 70 years old and fit for intensive chemotherapy. A leukemia-associated immunophenotype (LAIP) defined by multiparameter flow cytometry (MFC) according to the 2022 ELN recommendation (2022 ELN) is necessary for enrollment in this trial.
All eligible participants receive the 3+7 regimen. Pretreatment with hydroxyurea is permitted to manage leukocytosis.
LAIP+ cells are enumerated on EDTA-anticoagulated peripheral blood collected before chemotherapy on days 1 and 4 of the first induction cycle (each cycle is 28 days). At least 100 circulating LAIP+ cells per microliter on day 1 are required as inclusion criteria to ensure optimal sensitivity. The EPBCR is calculated on day 4 of the first induction regimen as a ratio converted to a logarithmic scale between the absolute peripheral blood LAIP+ cell count on day 1 (baseline) and day 4. A cut-off of 1.5 log is decisional to assign participants to treatment modalities. Participants with EPBCR>1.5 log (EPBCRhigh) complete the 3+7 regimen and are managed according to standard clinical practice. Participants with EPBCR≦1.5 log (EPBCRlow) receive intensified treatment with venetoclax orally along with the standard 3+7 regimen on days 5-14. A venetoclax dose ramp-up schedule is required in the first induction therapy.
After two cycles of induction therapy, participants who fail to achieve composite complete remission (CR/CRi, CRc) may receive an alternative regimen per their physicians' decision.
After CR/CRi is achieved, participants proceed with consolidation therapy or allo-HSCT based on their 2022 ELN risk categories. Participants with favorable risk should go through four cycles (each cycle is 28 days) of consolidation therapy, those with adverse risk should go through allogeneic hematopoietic stem cell transplantation (allo-HSCT) after two cycles of consolidation therapy, and those with intermediate risk can receive allo-HSCT after two cycles of consolidation therapy if suitable donors are available or continue with four cycles of consolidation therapy. Participants receive four cycles of consolidation regimen of intermediate-dose cytarabine for age >60 years old or high-dose cytarabine for age >60 years old. The consolidation therapy will be combined with venetoclax in the EPBCRlow cohort and not in the EPBCRhigh cohort.
After consolidation, participants will receive maintenance therapy per their physicians' decision and be observed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Assigned interventions | Experimental | Drug: Venetoclax, Drug: Idarubincin, Drug: CytarabineParticipants with EPBCR>1.5 log (EPBCRhigh) complete the 3+7 regimen and are managed according to standard clinical practice. Participants with EPBCR≦1.5 log (EPBCRlow) receive intensified treatment with venetoclax orally along with the standard 3+7 regimen on days 5-14. A venetoclax dose ramp-up schedule is required in the first induction therapy. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Newly diagnosed AML, except for the APL subtype, according to the 2022 World Health Organization classification (WHO 2022 criteria)
- Age ≥18 years and ≤70 years
- Eligible for intensive chemotherapy
- No prior chemotherapy for AML except hydroxyurea for up to 14 days during the diagnostic screening phase for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell [WBC] counts>25x10^9/L)
- Eastern Cooperative Oncology Group (ECOG) performance status≤2
Key exclusion criteria (25 listed)
- AML with BCR-ABL1 or myeloid blast crisis of CML
- Participants who have received prior treatment for AML with chemotherapy, hypomethylating agents, or venetoclax
- Participants who are ineligible for intensive induction chemotherapy:
- Participants with a prior history of MDS, MPN, or MDS/MPN
- Participants with other concurrent malignant tumors on treatment, except for:
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 |
|---|---|---|
| VenetoclaxAlso: Bcl-2 inhibitorsVenetoclax in the EPBCRlow cohort will be added to the ongoing 3+7 regimen. In the first induction cycle: venetoclax needs to be ramped up: 100 mg on day 5, 200mg on day 6, and 400mg on days 7-14, orally once daily. In the second induction (if required), venetoclax 400mg will be administered orally once daily on days 5-14 without a dose ramp-up schedule. Venetoclax in the EPBCRlow cohort during consolidation therapy: 400mg on days 1-7, orally once daily, along with the consolidation chemotherapy. | Drug | Assigned interventions |
| IdarubincinAlso: IDAIdarubicin (IDA): 10mg/m^2/d (age <60 years old) or 6mg/m^2/d on days 1-3, intravenously (IV). | Drug | Assigned interventions |
| CytarabineAlso: Ara-CDuring induction therapy: 100mg/m2/d on days 1-7, IV. During consolidation therapy: intermediate-dose cytarabine for age >55 years old: 1.0g/m^2 q12h on days 1-3, high-dose cytarabine for age ≦55 years old: 2g/m2 q12h on days 1-3. | Drug | Assigned interventions |
Primary outcome
CRc rate after one cycle of induction therapy
Time frame: Up to one month
The proportion of participants achieving CR/CRi by the initiation of next cycle of therapy (each cycle is 28 days).
5 secondary outcomes
CRc rate after two cycle of induction therapy
Time frame: Up to 2 months
CRMRD-Rate
Time frame: Up to 2 months
Event-free survival (EFS)
Time frame: Up to 12 months
Relapse free survival (RFS)
Time frame: Up to 24 months
Overall survival Overall survival (OS)
Time frame: Up to 24 months
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 12 Nov 2024.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Venetoclax, Idarubincin and Cytarabine in people with Leukemia and Leukemia, Myeloid, run by Affiliated Hospital of Nantong 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 15 inclusion and 25 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 12 Nov 2024. 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.
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 Yingxin Sun, Dr (+86-13646249970, syx20194132088@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CRc rate after one cycle of induction therapy (time frame: Up to one month). 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 12 Nov 2024.