Acute Myeloid LeukemiaPhase 3NCT05382390
Dual Growth Factor (rhTPO + G-CSF) and Chemotherapy Combination Regimen in Acute Myeloid Leukemia: Study Protocol for a Randomized Controlled Trial
A Phase 3 study testing rhTPO and Decitabine in people with Acute Myeloid Leukemia, run by Huihan Wang at 1 site in China.
Trial summary
Acute myeloid leukemia (AML) is a disease affecting older adults, although optimal strategies for treating such patients remain unclear. This prospective phase II, openlabel, multicenter study was designed to assess the efficacy and safety of two hematologic growth factors, recombinant human thrombopoietin (rhTPO) and… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- rhTPO and Decitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteChina
- Study dates
- 21 Jan 2022to 21 Jan 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 60 or above, male or female; Acute Myeloid Leukemia (non-M3) diagnosed according to the 2008 World Health Organization (WHO) diagnostic criteria for myeloid malignancies; Newly diagnosed, no treatment for anti-leukemia; The Eastern Cooperative Oncology Group（ECOG） status score is 0 to 3 points; Expected survival time ≥ 3 months; No serious heart, lung, liver or kidney disease; History of no thromboembolism Ability to understand and be willing to sign the informed consent form of this trial.
Who cannot join
- used to be allergic to the drugs contained in the protocol or to drugs similar in chemical structure to the test drugs; serious active infections; Patients with extramedullary lesions; Patients who use drugs and long-term alcohol abuse to influence the evaluation of test results; Inability to obtain informed consent and cannot complete the trial treatment and examination procedures because of mental illness or other conditions Patients with clinically significant corrected QT interval (QTc) prolongation (male > 450ms, female > 470ms), Ventricular Tachycardia (VT), Atrial Fibrillation (AF), grade II or higher heart block, Myocardial Infarction (MI) within 1 year, Congestive Heart Failure (CHF), coronary heart disease with symptoms who need medical treatment; Abnormal liver function (total bilirubin > 1.5 times the upper limit of normal value, Alanine aminotransferase(ALT) / Aspartate aminotransferase (AST) >2.5 times the upper limit of normal value or ALT / AST in patients with liver invasion > 5 times the upper limit of normal value of normal), abnormal renal function (serum Creatinine > 1.5 times the upper limit of normal); The investigator determine that the participants are not suitable
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
ShengJing Hospital of China Medical University
Shenyang, Liaoning, 110004
Huihan Wang, Doctor, +86 18940256966, wanghh24115@outlook.com
About this study
Acute myeloid leukemia (AML) is a disease affecting older adults, although optimal strategies for treating such patients remain unclear. This prospective phase II, openlabel, multicenter study was designed to assess the efficacy and safety of two hematologic growth factors, recombinant human thrombopoietin (rhTPO) and granulocyte colonystimulating factor (G-CSF), in combination with decitabine, cytarabine, and aclarubicin (D-CTAG regimen) to treat older adults with newly diagnosed AML (Identifier: NCT04168138). The above agents were administered as follows: decitabine (15 mg/m2 daily, days 1-5); low-dose cytarabine (10 mg/m2 q12 h, days 3-9); rhTPO (15,000U daily, days 2, 4, 6, 8, 10-24 or until >50×109/L platelets); aclarubicin (14 mg/m2 daily, days 3-6); and G-CSF (300 μg daily, days 2-9). We concurrently monitored historic controls treated with decitabine followed by cytarabine, aclarubicin, and G-CSF (D-CAG) only. After the first D-CTAG cycle, the overall response rate (ORR) was 84.2% (16/19), including 13 (73.7%) complete remissions (CRs) and three (15.8%) partial remissions. This CR rate surpassed that of the D-CAG treatment (p < 0.05). Median overall survival (OS) time in the D-CTAG group was 20.2 months (range, 4-31 months), compared with 14 months in the D-CAG group, and 1-year OS was 78%. The proportion of those experiencing grade III-IV thrombocytopenia was significantly lower for D-CTAG (57.9%) than for D-CAG (88.4%; p < 0.05). Ultimately, the curative effect of adding rhTPO was not inferior to that of D-CAG, and D-CTAG proved safer for elderly patients, especially in terms of hematologic toxicity. A prospective phase III randomized study is warranted to confirm these observations.
Read the detailed description
Acute myeloid leukemia (AML) is one of the most common hematologic malignancies and affects older adults. The median age at diagnosis is 67 years. As the elderly increasingly account for a greater population percentage, AML is becoming more problematic. During the past 30 years, outcomes have improved for younger patients, whereas the prospects for older adults (> 60 years) have remained poor. The response rate in older adults given standard induction regimens is < 50%, and median overall survival (OS) is < 1 year. Older adults elderly are also inordinately burdened by unfavorable cytogenetic defects, medical comorbidities, and reduced tolerability to intensive chemotherapeutic protocols. These vulnerabilities predispose older adults to poorer outcomes than their younger counterparts, conferring lower response rates and shortened survival times (progression-free and overall survival [OS]). Safe and effective treatments for elderly patients with AML are thus urgently needed.
In 2000, Saito et al introduced a regimen of granulocyte colony-stimulating factor (G-CSF) plus low-dose cytarabine (ara-C) and aclarubicin (ACR) for use in this setting (CAG regimen), in an attempt to incorporate a hematologic growth factor in AML induction therapy, rather than relying on supportive care. The addition of decitabine, a demethylation agent, further improved the prognosis, yielding a 10-month median OS. This successful use of G-CSF in an induction regimen for AML confirmed its utility, helping to increase efficacy and reduce side effects in elderly patients.
Thrombopoietin (TPO) is a major factor in regulating megakaryocytic proliferation, maturation, and platelet formation. Recombinant human TPO (rhTPO) has been approved by China's State Food and Drug Administration to treat thrombocytopenia after chemotherapy. TPO and c-MPL receptors are also involved in various physiologic processes, such as mitigating myocardial injury, nerve repair, vascular regeneration, sex hormone secretion, and immune regulation. However, the role of rhTPO in an induction regimen for AML is unreported as yet.
To determine if adding rhTPO to D-CAG (G-CSF) will increase the overall response rate (ORR) while decreasing the side effect of toxic agents, we designed a regimen of rhTPO and G-CSF in combination with decitabine, cytarabine, and aclarubicin (D-CTAG regimen). This trial aimed to determine the safety and efficacy of this D-CTAG regimen as a treatment for older adult patients with newly diagnosed AML.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- rhTPO, Decitabine
- 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.
rhTPODrug
Also called Decitabine, Aclarubicin, G-CSF, Cytarabine
decitabine (15 mg/m2 daily, days 1-5); low-dose cytarabine (10 mg/m2 q12 h, days 3-9); rhTPO (15,000 U daily, days 2, 4, 6, 8, and 10-24 or until a platelet count > 50 × 109/L was observed); aclarubicin (14 mg/m2 daily, days 3-6); and G-CSF (300 μg daily, days 2-9).
DecitabineDrug
Also called Aclarubicin, G-CSF, Cytarabine
decitabine (15 mg/m2 daily, days 1-5); low-dose cytarabine (10 mg/m2 q12 h, days 3-9); aclarubicin (14 mg/m2 daily, days 3-6); and G-CSF (300 μg daily, days 2-9).
| Study group | Role | What they receive |
|---|---|---|
| lderly Patients With Acute Myeloid Leukemia DCTAG | Experimental | decitabine (15 mg/m2 daily, days 1-5); low-dose cytarabine (10 mg/m2 q12 h, days 3-9); rhTPO (15,000 U daily, days 2, 4, 6, 8, and 10-24 or until a platelet count > 50 × 109/L was observed); aclarubicin (14 mg/m2 daily, days 3-6); and G-CSF (300 μg daily, days 2-9). Receives: Drug: rhTPO; Drug: Decitabine |
| lderly Patients With Acute Myeloid Leukemia | Other | decitabine (15 mg/m2 daily, days 1-5); low-dose cytarabine (10 mg/m2 q12 h, days 3-9); aclarubicin (14 mg/m2 daily, days 3-6); and G-CSF (300 μg daily, days 2-9). Receives: Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall survival (OS)
overall survival
Measured: 2 years after the end of treatment of the last patient enrolled
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2022
- Study start21 Jan 2022
- Primary completion21 Jan 2024 (estimated)
- Study completion21 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Huihan Wang
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Huihan Wang, Shengjing Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05382390
- Sponsor's protocol ID
- hhhWang
- Status last verified
- May 2022
- First submitted
- 16 May 2022
- Last updated
- 19 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
- 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 19 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dual Growth Factor (rhTPO + G-CSF) and Chemotherapy Combination Regimen in Acute Myeloid Leukemia: Study Protocol for a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05382390
- Acronym / sponsor ID
- hhhWang
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Huihan WangUniversity, hospital or other
- Study start
- 21 Jan 2022 (actual)
- Primary completion
- 21 Jan 2024 (estimated)
- Study completion
- 21 Jan 2026 (estimated)
- First posted
- 19 May 2022 (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.
Acute myeloid leukemia (AML) is a disease affecting older adults, although optimal strategies for treating such patients remain unclear. This prospective phase II, openlabel, multicenter study was designed to assess the efficacy and safety of two hematologic growth factors, recombinant human thrombopoietin (rhTPO) and granulocyte colonystimulating factor (G-CSF), in combination with decitabine, cytarabine, and aclarubicin (D-CTAG regimen) to treat older adults with newly diagnosed AML (Identifier: NCT04168138). The above agents were administered as follows: decitabine (15 mg/m2 daily, days 1-5); low-dose cytarabine (10 mg/m2 q12 h, days 3-9); rhTPO (15,000U daily, days 2, 4, 6, 8, 10-24 or until >50×109/L platelets); aclarubicin (14 mg/m2 daily, days 3-6); and G-CSF (300 μg daily, days 2-9). We concurrently monitored historic controls treated with decitabine followed by cytarabine, aclarubicin, and G-CSF (D-CAG) only. After the first D-CTAG cycle, the overall response rate (ORR) was 84.2% (16/19), including 13 (73.7%) complete remissions (CRs) and three (15.8%) partial remissions. This CR rate surpassed that of the D-CAG treatment (p < 0.05). Median overall survival (OS) time in the D-CTAG group was 20.2 months (range, 4-31 months), compared with 14 months in the D-CAG group, and 1-year OS was 78%. The proportion of those experiencing grade III-IV thrombocytopenia was significantly lower for D-CTAG (57.9%) than for D-CAG (88.4%; p < 0.05). Ultimately, the curative effect of adding rhTPO was not inferior to that of D-CAG, and D-CTAG proved safer for elderly patients, especially in terms of hematologic toxicity. A prospective phase III randomized study is warranted to confirm these observations.
Detailed description
Acute myeloid leukemia (AML) is one of the most common hematologic malignancies and affects older adults. The median age at diagnosis is 67 years. As the elderly increasingly account for a greater population percentage, AML is becoming more problematic. During the past 30 years, outcomes have improved for younger patients, whereas the prospects for older adults (> 60 years) have remained poor. The response rate in older adults given standard induction regimens is < 50%, and median overall survival (OS) is < 1 year. Older adults elderly are also inordinately burdened by unfavorable cytogenetic defects, medical comorbidities, and reduced tolerability to intensive chemotherapeutic protocols. These vulnerabilities predispose older adults to poorer outcomes than their younger counterparts, conferring lower response rates and shortened survival times (progression-free and overall survival [OS]). Safe and effective treatments for elderly patients with AML are thus urgently needed.
In 2000, Saito et al introduced a regimen of granulocyte colony-stimulating factor (G-CSF) plus low-dose cytarabine (ara-C) and aclarubicin (ACR) for use in this setting (CAG regimen), in an attempt to incorporate a hematologic growth factor in AML induction therapy, rather than relying on supportive care. The addition of decitabine, a demethylation agent, further improved the prognosis, yielding a 10-month median OS. This successful use of G-CSF in an induction regimen for AML confirmed its utility, helping to increase efficacy and reduce side effects in elderly patients.
Thrombopoietin (TPO) is a major factor in regulating megakaryocytic proliferation, maturation, and platelet formation. Recombinant human TPO (rhTPO) has been approved by China's State Food and Drug Administration to treat thrombocytopenia after chemotherapy. TPO and c-MPL receptors are also involved in various physiologic processes, such as mitigating myocardial injury, nerve repair, vascular regeneration, sex hormone secretion, and immune regulation. However, the role of rhTPO in an induction regimen for AML is unreported as yet.
To determine if adding rhTPO to D-CAG (G-CSF) will increase the overall response rate (ORR) while decreasing the side effect of toxic agents, we designed a regimen of rhTPO and G-CSF in combination with decitabine, cytarabine, and aclarubicin (D-CTAG regimen). This trial aimed to determine the safety and efficacy of this D-CTAG regimen as a treatment for older adult patients with newly diagnosed AML.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| lderly Patients With Acute Myeloid Leukemia DCTAG | Experimental | Drug: rhTPO, Drug: Decitabinedecitabine (15 mg/m2 daily, days 1-5); low-dose cytarabine (10 mg/m2 q12 h, days 3-9); rhTPO (15,000 U daily, days 2, 4, 6, 8, and 10-24 or until a platelet count > 50 × 109/L was observed); aclarubicin (14 mg/m2 daily, days 3-6); and G-CSF (300 μg daily, days 2-9). |
| lderly Patients With Acute Myeloid Leukemia | Other | Drug: Decitabinedecitabine (15 mg/m2 daily, days 1-5); low-dose cytarabine (10 mg/m2 q12 h, days 3-9); aclarubicin (14 mg/m2 daily, days 3-6); and G-CSF (300 μg daily, days 2-9). |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Age 60 or above, male or female; Acute Myeloid Leukemia (non-M3) diagnosed according to the 2008 World Health Organization (WHO) diagnostic criteria for myeloid malignancies; Newly diagnosed, no treatment for anti-leukemia; The Eastern Cooperative Oncology Group（ECOG） status score is 0 to 3 points; Expected survival time ≥ 3 months; No serious heart, lung, liver or kidney disease; History of no thromboembolism Ability to understand and be willing to sign the informed consent form of this trial.
Key exclusion criteria (1 listed)
- used to be allergic to the drugs contained in the protocol or to drugs similar in chemical structure to the test drugs; serious active infections; Patients with extramedullary lesions; Patients who use drugs and long-term alcohol abuse to influence the evaluation of test results; Inability to obtain informed consent and cannot complete the trial treatment and examination procedures because of mental illness or other conditions Patients with clinically significant corrected QT interval (QTc) prolongation (male > 450ms, female > 470ms), Ventricular Tachycardia (VT), Atrial Fibrillation (AF), grade II or higher heart block, Myocardial Infarction (MI) within 1 year, Congestive Heart Failure (CHF), coronary heart disease with symptoms who need medical treatment; Abnormal liver function (total bilirubin > 1.5 times the upper limit of normal value, Alanine aminotransferase(ALT) / Aspartate aminotransferase (AST) >2.5 times the upper limit of normal value or ALT / AST in patients with liver invasion > 5 times the upper limit of normal value of normal), abnormal renal function (serum Creatinine > 1.5 times the upper limit of normal); The investigator determine that the participants are not suitable
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 |
|---|---|---|
| rhTPOAlso: Decitabine, Aclarubicin, G-CSF, Cytarabinedecitabine (15 mg/m2 daily, days 1-5); low-dose cytarabine (10 mg/m2 q12 h, days 3-9); rhTPO (15,000 U daily, days 2, 4, 6, 8, and 10-24 or until a platelet count > 50 × 109/L was observed); aclarubicin (14 mg/m2 daily, days 3-6); and G-CSF (300 μg daily, days 2-9). | Drug | lderly Patients With Acute Myeloid Leukemia DCTAG |
| DecitabineAlso: Aclarubicin, G-CSF, Cytarabinedecitabine (15 mg/m2 daily, days 1-5); low-dose cytarabine (10 mg/m2 q12 h, days 3-9); aclarubicin (14 mg/m2 daily, days 3-6); and G-CSF (300 μg daily, days 2-9). | Drug | lderly Patients With Acute Myeloid Leukemia, lderly Patients With Acute Myeloid Leukemia DCTAG |
Primary outcome
overall survival (OS)
Time frame: 2 years after the end of treatment of the last patient enrolled
overall survival
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2022.
- 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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing rhTPO and Decitabine in people with Acute Myeloid Leukemia, run by Huihan Wang 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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 19 May 2022. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Huihan Wang, Doctor (+86 18940256966, wanghh24115@outlook.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall survival (OS) (time frame: 2 years after the end of treatment of the last patient enrolled). 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 19 May 2022.