Acute Myeloid LeukemiaPhase 2NCT03080766
The Use of Decitabine as Induction Therapy for Acute Myeloid Leukemia With Complex and/or Monosomal Karyotype
A Phase 2 study testing Decitabine in people with Acute Myeloid Leukemia and Complex Karyotype, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
Acute myeloid leukemia (AML) is a heterogeneous group of diseases with distinct clinicopathologic features sharing in common an abnormal increase in myeloblasts in blood and bone marrow (BM). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Myeloid Leukemia, Complex Karyotype
- What is being tested?
- Decitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Mar 2017to 28 Dec 2021
- Phase
- Phase 2
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (age 18-65 years old) with CK/MK AML at diagnosis
- De novo or secondary AML is allowed
- ECOG performance ≤ 2
- Subjects with adequate liver, pancreatic and renal function at screening as demonstrated by :Direct bilirubin < 2 x upper limit of laboratory normal (ULN) Alanine aminotransferase (ALT) < 2.5 x ULN MDRD-eGRF > 30ml/min/1.73m2
- Negative serum / urine pregnancy test within 7 days before starting study treatment in women with childbearing potential.
- Subjects with ability to understand the protocol and signed a written informed consent document prior to the participation of the study.
Who cannot join
- Patients with CK/MK AML who have received standard induction chemotherapy before
- Patients with active and uncontrolled infection.
- Patients with concurrent severe and uncontrolled concomitant medical conditions that could cause unacceptable safety risk or compromise compliance with the protocol.
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
The University of Hong Kong
Hong Kong
Chunxiao Zhang, SC, 852-22554361, chunxiao@hku.hk
About this study
Acute myeloid leukemia (AML) is a heterogeneous group of diseases with distinct clinicopathologic features sharing in common an abnormal increase in myeloblasts in blood and bone marrow (BM). In about 5-10% patients, the myeloblasts exhibit chromosomal abnormalities (complex and/or monosomal karyotype, CK/MK*) that are associated with refractoriness to conventional chemotherapy and an extremely bad prognosis.
Standard induction chemotherapy for AML comprises daunorubicin and cytarabine, the "7+3" regimen. However, treatment is largely ineffective for CK/MK AML with a temporary clearance of blasts achieved in only 30-40% cases and the cumulative toxicities resulting from repeated courses of chemotherapy have significantly increased the morbidity and mortality risks in subsequent allogeneic BMT. Therefore, standard treatment is unsatisfactory and there is an unmet clinical need for more effective and less toxic induction regimen.
Both previous and recent studies showed that 10 day course of decitabine (20 mg/m2/day) induced remission in 70-100% patients with CK/MK AML, particularly those with TP53 mutations. In this study, patients with CK/MK AML will be treated with decitabine to induce remission. Bone marrow examination will be performed after each course until complete clearance of blasts or disease progression. Patients achieving CR/CRi (see below) will continue to receive 4 more courses, after which patients eligible for BMT and for whom donors are available will receive curative BMT. We reckon that the time it takes for 4 courses of decitabine will suffice for transplantation workup in HK. . Patients ineligible for BMT will continue to receive decitabine until leukemia progression. The response rate, leukemia free survival (LFS), overall survival (OS) and percentage of patients who can be bridged to BMT will be compared with historical 7+3 regimen control.
Read the detailed description
This is an open-label interventional study to study the use of decitabine as induction therapy for acute myeloid leukemia with complex and/or monosomal karyotype.
Subjects will receive decitabine for every 28 days, until disease progression or a bone marrow transplantation is carried out, in the schedule as below:
Cycle 1:
Receive decitabine for 10 days
Cycle 2 and Cycle 3:
Based on the result of bone marrow examination, subjects may receive decitabine for 5 days or 10 days
Cycle 4 until disease progression:
Rdecitabine for 5 days. Subjects may also resume a 10 day treatment after cycle 6 if their physician judged as appropriate.
The drug will then be administrated intravenously.
Blood will be drawn every 7 days and bone marrow extraction would be done on Day 28 (+/- 3days) from the day 1 of each cycle of treatment for examination.
- Conditions
- Acute Myeloid Leukemia, Complex Karyotype
- Being tested
- 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.
DecitabineDrug
Also called Dacogen
Decitabine (trade name Dacogen®) is a cytidine deoxynucleoside analogue, which selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation that can result in reactivation of tumor suppressor genes, induction of cellular differentiation or cellular senescence followed by programmed cell death.
| Study group | Role | What they receive |
|---|---|---|
| decitabine | Experimental | Decitabine is a white to almost white powder for concentrate for solution for infusion. It is supplied as a lyophilized preparation in a clear colorless 20ml glass vial containing 50 mg decitabine.
The concentrate should be aseptically reconstituted with 10 ml of water for injections. After reconstitution, the concentrate must be diluted within 15 minutes using cooled infusion fluids and completely administered to patients within 5 hours.
The drug will then be administrated intravenously.
Dosage 20 mg/m2
28-day course, for each course, receive decitabine for 10 days Receives: Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete remission (CR):
No increase in blasts in BM or PB (<5% of total nucleated cells), with absolute neutrophil count ≥ 1x109/L and platelet count ≥ 100 x109/L.
Measured: up to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2017
- Study start1 Mar 2017
- Primary completion30 Sep 2021 (estimated)
- Study completion28 Dec 2021 (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.
- More trials run by The University of Hong KongThe 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
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen, LP
- Responsible party
- Principal investigator, Dr. Anskar Y.H. Leung, The University of Hong Kong
- Investigators
- Anskar Leung, Professor, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03080766
- Sponsor's protocol ID
- AML002
- Status last verified
- Apr 2021
- First submitted
- 22 Feb 2017
- Last updated
- 28 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Decitabine as Induction Therapy for Acute Myeloid Leukemia With Complex and/or Monosomal Karyotype
- ClinicalTrials.gov ID
- NCT03080766
- Acronym / sponsor ID
- AML002
- Conditions
- Acute Myeloid Leukemia, Complex Karyotype
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- Janssen, LP
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 30 Sep 2021 (estimated)
- Study completion
- 28 Dec 2021 (estimated)
- First posted
- 15 Mar 2017 (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 heterogeneous group of diseases with distinct clinicopathologic features sharing in common an abnormal increase in myeloblasts in blood and bone marrow (BM). In about 5-10% patients, the myeloblasts exhibit chromosomal abnormalities (complex and/or monosomal karyotype, CK/MK*) that are associated with refractoriness to conventional chemotherapy and an extremely bad prognosis.
Standard induction chemotherapy for AML comprises daunorubicin and cytarabine, the "7+3" regimen. However, treatment is largely ineffective for CK/MK AML with a temporary clearance of blasts achieved in only 30-40% cases and the cumulative toxicities resulting from repeated courses of chemotherapy have significantly increased the morbidity and mortality risks in subsequent allogeneic BMT. Therefore, standard treatment is unsatisfactory and there is an unmet clinical need for more effective and less toxic induction regimen.
Both previous and recent studies showed that 10 day course of decitabine (20 mg/m2/day) induced remission in 70-100% patients with CK/MK AML, particularly those with TP53 mutations. In this study, patients with CK/MK AML will be treated with decitabine to induce remission. Bone marrow examination will be performed after each course until complete clearance of blasts or disease progression. Patients achieving CR/CRi (see below) will continue to receive 4 more courses, after which patients eligible for BMT and for whom donors are available will receive curative BMT. We reckon that the time it takes for 4 courses of decitabine will suffice for transplantation workup in HK. . Patients ineligible for BMT will continue to receive decitabine until leukemia progression. The response rate, leukemia free survival (LFS), overall survival (OS) and percentage of patients who can be bridged to BMT will be compared with historical 7+3 regimen control.
Detailed description
This is an open-label interventional study to study the use of decitabine as induction therapy for acute myeloid leukemia with complex and/or monosomal karyotype.
Subjects will receive decitabine for every 28 days, until disease progression or a bone marrow transplantation is carried out, in the schedule as below:
Cycle 1:
Receive decitabine for 10 days
Cycle 2 and Cycle 3:
Based on the result of bone marrow examination, subjects may receive decitabine for 5 days or 10 days
Cycle 4 until disease progression:
Rdecitabine for 5 days. Subjects may also resume a 10 day treatment after cycle 6 if their physician judged as appropriate.
The drug will then be administrated intravenously.
Blood will be drawn every 7 days and bone marrow extraction would be done on Day 28 (+/- 3days) from the day 1 of each cycle of treatment for examination.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| decitabine | Experimental | Drug: DecitabineDecitabine is a white to almost white powder for concentrate for solution for infusion. It is supplied as a lyophilized preparation in a clear colorless 20ml glass vial containing 50 mg decitabine. The concentrate should be aseptically reconstituted with 10 ml of water for injections. After reconstitution, the concentrate must be diluted within 15 minutes using cooled infusion fluids and completely administered to patients within 5 hours. The drug will then be administrated intravenously. Dosage 20 mg/m2 28-day course, for each course, receive decitabine for 10 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adult patients (age 18-65 years old) with CK/MK AML at diagnosis
- De novo or secondary AML is allowed
- ECOG performance ≤ 2
- Subjects with adequate liver, pancreatic and renal function at screening as demonstrated by :Direct bilirubin < 2 x upper limit of laboratory normal (ULN) Alanine aminotransferase (ALT) < 2.5 x ULN MDRD-eGRF > 30ml/min/1.73m2
- Negative serum / urine pregnancy test within 7 days before starting study treatment in women with childbearing potential.
Key exclusion criteria (3 listed)
- Patients with CK/MK AML who have received standard induction chemotherapy before
- Patients with active and uncontrolled infection.
- Patients with concurrent severe and uncontrolled concomitant medical conditions that could cause unacceptable safety risk or compromise compliance with the protocol.
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 |
|---|---|---|
| DecitabineAlso: DacogenDecitabine (trade name Dacogen®) is a cytidine deoxynucleoside analogue, which selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation that can result in reactivation of tumor suppressor genes, induction of cellular differentiation or cellular senescence followed by programmed cell death. | Drug | decitabine |
Primary outcome
Complete remission (CR):
Time frame: up to 16 weeks
No increase in blasts in BM or PB (<5% of total nucleated cells), with absolute neutrophil count ≥ 1x109/L and platelet count ≥ 100 x109/L.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2021.
- Individual participant dataSharing planned: Undecided
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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.
Anskar Leung, Professor principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Decitabine in people with Acute Myeloid Leukemia and Complex Karyotype, run by The University of Hong Kong at 1 site in Hong Kong.
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 6 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: status not confirmed, as of the sponsor's last update on 28 Apr 2021. 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 Hong Kong. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Crosby Lu, SC (852-22554361, khlu@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete remission (CR): (time frame: up to 16 weeks). 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 28 Apr 2021.