Acute Lymphocytic Leukemia, Adult B-CellPhase 3NCT04375683
Study of Efficacy and Safety of Flumatinib Combined With Chemotherapy in Ph Positive ALL
A Phase 3 study testing Flumatinib in people with Acute Lymphocytic Leukemia, Adult B-Cell and BCR-ABL1 Fusion Protein Expression, run by Zhongda Hospital at 2 sites in China.
Trial summary
Philadelphia chromosome (BCR-ABL1, Ph) is the most common genetic abnormality in acute lymphoblastic leukemia (ALL) and an independent prognostic risk factor. With the increase of age, the incidence of patients over 60 years old can reach 50%, whose 5-year overall survival rate was less than 20%. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Lymphocytic Leukemia, Adult B-Cell, BCR-ABL1 Fusion Protein Expression
- What is being tested?
- Flumatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 2 sitesChina
- Study dates
- 1 Mar 2020to 30 Dec 2022
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed as Ph positive ALL
- Signing informed consent voluntarily
Who cannot join
- Severe mental disorder
- Uncontrolled heart disease
- Be allergic to flumatinib or other research drugs
- More than 80 years old
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
Department of Hematology, Zhongda Hospital Southeast University, Institute of Hematology Southeast University
Nanjing, Jiangsu, 210009
Zheng Ge, PhD. MD., 025-83262468 ext. +86, gezheng2008@163.com
- Recruiting
Department of Hematology, Zhongda Hospital Southeast University, Institute of Hematology Southeast University
Nanjing, Jiangsu, 210009
Zheng Ge, M.D, Ph.D, 02583262468, Janege879@hotmail.com
About this study
Official title: A Study of Efficacy and Safety of Flumatinib Combined With Chemotherapy in the Treatment of Ph Positive Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring
Philadelphia chromosome (BCR-ABL1, Ph) is the most common genetic abnormality in acute lymphoblastic leukemia (ALL) and an independent prognostic risk factor. With the increase of age, the incidence of patients over 60 years old can reach 50%, whose 5-year overall survival rate was less than 20%.
With the application of tyrosine kinase inhibitor (TKI), the prognosis of Ph positive ALL patients is greatly improved. At present, TKI combined with chemotherapy has become the first-line treatment recommended in the guideline of Ph positive ALL patients.
Read more
However, with the use of imatinib, more and more patients develop drug resistant to imatinib. In addition, the clinical data showed that the MRD negative rate in patients treated with imatinib combined with hyper CVAD was only 22% three months later, which was far lower than 31% of the second generation TKI and 52% of the third generation TKI.
Second generation TKI dasatinib and nilotinib can overcome most imatinib resistant kinase region mutations. However, patients with severe hemocytopenia, infection or other complications are often unable to tolerate the standard chemotherapy. In addition, due to the high cost, some patients can't afford the long-term use.
Flumatinib is the first approved second generation TKI in China and a derivative of imatinib. Compared with imatinib, it introduced trifluoromethyl, substituted pyridine ring for benzene ring, and kept the direction of amide bond, which made the inhibitory effect of flumatinib on common kinase mutations significantly better than that of imatinib. In addition, compared with the second-generation TKI recommended in the first line of current guidelines, the incidence of quality of life related adverse reactions of flumatinib is lower, and no specific adverse reactions of the second-generation TKI have been reported.
We plan to enroll 28 patients with Ph positive ALL. All patients are diagnosed by morphology, immunology, cytogenetics and molecular biology (MICM). According to subjects' age, we will divide them into two groups. Subjects aged 60 years or older are received flumatinib and dose-adjusted VDCP or prednisone regimen. Subjects younger than 60 years are received flumatinib and hyper-CVAD regimen. MRD are examined on the 8th, 15th and 29th day after chemotherapy. Then, MRD will be monitored in the third, 6th, 9th, 12th, 15th, 18th, 21th and 24th months after chemotherapy to evaluate the effect.
Read the detailed description
Flumatinib + hyper-CVAD (younger than 60):
Induction therapy: Flumatinib 600mg per day, on an empty stomach; For cycles 1, 3, 5, and 7: cyclophosphamide (CTX) 300 mg/m² is given intravenously over 3 h every 12 h for six doses on days 1-3; a continuous daily infusion of sodium mercaptoethanesulfonate (Mesna) at 600 mg/m² per day for 24h starting 1h before CTX and completed approximately 12h after the final CTX dose; doxorubicin 50 mg/m² is given intravenously over 24 h on day 4; vincristine (VCR) 1.4 mg/m² (Maximum daily dose 2 mg) is intravenously on days 4 and 11; dexamethasone (Dex) 40 mg is given intravenously or orally on days 1-4 and days 11-14. For cycles 2, 4, 6, and 8: methotrexate (MTX) is given intravenously at 200 mg/m² over 2 h, followed by 800 mg/m² over 22 h on day 1; cytarabine (Ara-C) 3 g/m² is given intravenously over 3 h every 12 h for four doses on days 2-3; citrovorum 50 mg is given intravenously, followed by 15 mg every 6 h for eight doses beginning 12 h after MTX completion. Prophylactic intrathecal therapy will be given after complete remission.
Maintenance therapy (given for 2 years): intravenous VCR 1.4 mg/m² on day 1 (Maximum daily dose 2 mg), every three months; oral dexamethasone 8mg/m² on days 1-7, every three months; oral 6-MP 60mg/m² on days 1-7, every month; oral MTX 20mg/m² on day 8, every month; and daily flumatinib at 600 mg. Months 6 and 13 of maintenance were intensification courses of hyper-CVAD and flumatinib.
Flumatinib + dose-adjusted VDCP (fit group, 60 years or older):
Induction therapy: flumatinib 600mg per day, on an empty stomach; vincristine (VCR) 1.4mg/m2/d (maximum daily dose 2mg) is given intravenously on day 1, 8, 15, 22; daunorubicin (DNR) 30mg/m2/d is given intravenously on day 1, 8, 15, 22 (if blasts of day 15 lower than 20%, DNR is not needed on day 15 and 22); cyclophosphamide (CTX) 400mg/m2/d is given intravenously on day 1,8,15 and 22; Prednisone 60mg/m2/d is given orally every other day for day 1-22. Prophylactic intrathecal therapy will be given after complete remission.
Consolidation therapy: flumatinib 600mg per day; daunorubicin (DNR) 40mg/m2 is given intravenously on day 1; cytarabine (Ara-C) 60mg/m2 is given intravenously on day 1-5; L-Asparaginasum (L-Asp) 500U/kg is given intravenously on day 6-10. If complete remission (CR) on day 28, a consolidation chemotherapy will be given on day 35; if not, we will give it as salvage therapy; And if CR is achieved after salvage therapy, another consolidation chemotherapy will be given.
Maintenance therapy (given for 2 years): intravenous VCR 1.4 mg/m² on day 1 (Maximum daily dose 2 mg), every three months; oral dexamethasone 8mg/m² on days 1-7, every three months; oral 6-MP 60mg/m² on days 1-7, every month; oral MTX 20mg/m² on day 8, every month; and daily flumatinib at 600 mg.
Flumatinib + Prednisone (unfit group, 60 years or older):
Prephase: Prednisone 60 mg/m2/d po, Day -7 to day -1. Induction therapy: flumatinib 600mg per day, on an empty stomach; Prednisone 60 mg/m2 per day day 1-24 and then tapered and stopped at day 32.
Maintenance therapy (given for 2 years): flumatinib 600mg per day.
- Being tested
- Flumatinib
- Keywords
- Flumatinib, minimal residual disease
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlumatinibDrug
Flumatinib 600mg per day, taken on empty stomach
| Study group | Role | What they receive |
|---|---|---|
| Ph-positive ALLs | Experimental | Subjects aged 60 years or older are received flumatinib and dose-adjusted VDCP or prednisone regimen. Subjects younger than 60 years are received flumatinib and hyper-CVAD regimen Receives: Drug: Flumatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
complete remission rate
blasts in bone marrow are less than 5%
Measured: day 28
minimal residual disease
MRD is measured by flow cytometry and qPCR
Measured: Change from MRD at 2 years
Secondary outcomes (1)
side effects
Number of participants with bone marrow suppression, nausea and vomiting, diarrhea, infection, and non-hematologic toxicity such as heart, liver, kidney and nervous system damage
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2020
- Study start1 Mar 2020
- Primary completion30 Dec 2022 (estimated)
- Study completion30 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphocytic Leukemia, Adult B-CellStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhongda Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ge Zheng, Zhongda Hospital
- Investigators
- Zheng Ge, PhD. MD., Study chair, Zhongda Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04375683
- Sponsor's protocol ID
- ZDYYGZ202003
- Status last verified
- Mar 2022
- First submitted
- 26 Apr 2020
- Last updated
- 24 Mar 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Efficacy and Safety of Flumatinib Combined With Chemotherapy in the Treatment of Ph Positive Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring
- ClinicalTrials.gov ID
- NCT04375683
- Acronym / sponsor ID
- ZDYYGZ202003
- Keywords
- Flumatinib, minimal residual disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- Zhongda HospitalUniversity, hospital or other
- Study start
- 1 Mar 2020 (actual)
- Primary completion
- 30 Dec 2022 (estimated)
- Study completion
- 30 Dec 2022 (estimated)
- First posted
- 5 May 2020 (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.
Philadelphia chromosome (BCR-ABL1, Ph) is the most common genetic abnormality in acute lymphoblastic leukemia (ALL) and an independent prognostic risk factor. With the increase of age, the incidence of patients over 60 years old can reach 50%, whose 5-year overall survival rate was less than 20%.
With the application of tyrosine kinase inhibitor (TKI), the prognosis of Ph positive ALL patients is greatly improved. At present, TKI combined with chemotherapy has become the first-line treatment recommended in the guideline of Ph positive ALL patients.
However, with the use of imatinib, more and more patients develop drug resistant to imatinib. In addition, the clinical data showed that the MRD negative rate in patients treated with imatinib combined with hyper CVAD was only 22% three months later, which was far lower than 31% of the second generation TKI and 52% of the third generation TKI.
Second generation TKI dasatinib and nilotinib can overcome most imatinib resistant kinase region mutations. However, patients with severe hemocytopenia, infection or other complications are often unable to tolerate the standard chemotherapy. In addition, due to the high cost, some patients can't afford the long-term use.
Flumatinib is the first approved second generation TKI in China and a derivative of imatinib. Compared with imatinib, it introduced trifluoromethyl, substituted pyridine ring for benzene ring, and kept the direction of amide bond, which made the inhibitory effect of flumatinib on common kinase mutations significantly better than that of imatinib. In addition, compared with the second-generation TKI recommended in the first line of current guidelines, the incidence of quality of life related adverse reactions of flumatinib is lower, and no specific adverse reactions of the second-generation TKI have been reported.
We plan to enroll 28 patients with Ph positive ALL. All patients are diagnosed by morphology, immunology, cytogenetics and molecular biology (MICM). According to subjects' age, we will divide them into two groups. Subjects aged 60 years or older are received flumatinib and dose-adjusted VDCP or prednisone regimen. Subjects younger than 60 years are received flumatinib and hyper-CVAD regimen. MRD are examined on the 8th, 15th and 29th day after chemotherapy. Then, MRD will be monitored in the third, 6th, 9th, 12th, 15th, 18th, 21th and 24th months after chemotherapy to evaluate the effect.
Detailed description
Flumatinib + hyper-CVAD (younger than 60):
Induction therapy: Flumatinib 600mg per day, on an empty stomach; For cycles 1, 3, 5, and 7: cyclophosphamide (CTX) 300 mg/m² is given intravenously over 3 h every 12 h for six doses on days 1-3; a continuous daily infusion of sodium mercaptoethanesulfonate (Mesna) at 600 mg/m² per day for 24h starting 1h before CTX and completed approximately 12h after the final CTX dose; doxorubicin 50 mg/m² is given intravenously over 24 h on day 4; vincristine (VCR) 1.4 mg/m² (Maximum daily dose 2 mg) is intravenously on days 4 and 11; dexamethasone (Dex) 40 mg is given intravenously or orally on days 1-4 and days 11-14. For cycles 2, 4, 6, and 8: methotrexate (MTX) is given intravenously at 200 mg/m² over 2 h, followed by 800 mg/m² over 22 h on day 1; cytarabine (Ara-C) 3 g/m² is given intravenously over 3 h every 12 h for four doses on days 2-3; citrovorum 50 mg is given intravenously, followed by 15 mg every 6 h for eight doses beginning 12 h after MTX completion. Prophylactic intrathecal therapy will be given after complete remission.
Maintenance therapy (given for 2 years): intravenous VCR 1.4 mg/m² on day 1 (Maximum daily dose 2 mg), every three months; oral dexamethasone 8mg/m² on days 1-7, every three months; oral 6-MP 60mg/m² on days 1-7, every month; oral MTX 20mg/m² on day 8, every month; and daily flumatinib at 600 mg. Months 6 and 13 of maintenance were intensification courses of hyper-CVAD and flumatinib.
Flumatinib + dose-adjusted VDCP (fit group, 60 years or older):
Induction therapy: flumatinib 600mg per day, on an empty stomach; vincristine (VCR) 1.4mg/m2/d (maximum daily dose 2mg) is given intravenously on day 1, 8, 15, 22; daunorubicin (DNR) 30mg/m2/d is given intravenously on day 1, 8, 15, 22 (if blasts of day 15 lower than 20%, DNR is not needed on day 15 and 22); cyclophosphamide (CTX) 400mg/m2/d is given intravenously on day 1,8,15 and 22; Prednisone 60mg/m2/d is given orally every other day for day 1-22. Prophylactic intrathecal therapy will be given after complete remission.
Consolidation therapy: flumatinib 600mg per day; daunorubicin (DNR) 40mg/m2 is given intravenously on day 1; cytarabine (Ara-C) 60mg/m2 is given intravenously on day 1-5; L-Asparaginasum (L-Asp) 500U/kg is given intravenously on day 6-10. If complete remission (CR) on day 28, a consolidation chemotherapy will be given on day 35; if not, we will give it as salvage therapy; And if CR is achieved after salvage therapy, another consolidation chemotherapy will be given.
Maintenance therapy (given for 2 years): intravenous VCR 1.4 mg/m² on day 1 (Maximum daily dose 2 mg), every three months; oral dexamethasone 8mg/m² on days 1-7, every three months; oral 6-MP 60mg/m² on days 1-7, every month; oral MTX 20mg/m² on day 8, every month; and daily flumatinib at 600 mg.
Flumatinib + Prednisone (unfit group, 60 years or older):
Prephase: Prednisone 60 mg/m2/d po, Day -7 to day -1. Induction therapy: flumatinib 600mg per day, on an empty stomach; Prednisone 60 mg/m2 per day day 1-24 and then tapered and stopped at day 32.
Maintenance therapy (given for 2 years): flumatinib 600mg per day.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ph-positive ALLs | Experimental | Drug: FlumatinibSubjects aged 60 years or older are received flumatinib and dose-adjusted VDCP or prednisone regimen. Subjects younger than 60 years are received flumatinib and hyper-CVAD regimen |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Diagnosed as Ph positive ALL
- Signing informed consent voluntarily
Key exclusion criteria (4 listed)
- Severe mental disorder
- Uncontrolled heart disease
- Be allergic to flumatinib or other research drugs
- More than 80 years old
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 |
|---|---|---|
| FlumatinibFlumatinib 600mg per day, taken on empty stomach | Drug | Ph-positive ALLs |
Primary outcome
complete remission rate
Time frame: day 28
blasts in bone marrow are less than 5%
minimal residual disease
Time frame: Change from MRD at 2 years
MRD is measured by flow cytometry and qPCR
1 secondary outcome
side effects
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2022.
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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.
Zheng Ge, PhD. MD. study chair
Zhongda Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Flumatinib in people with Acute Lymphocytic Leukemia, Adult B-Cell and BCR-ABL1 Fusion Protein Expression, run by Zhongda Hospital at 2 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 2 inclusion and 4 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 24 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 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 Zheng Ge, PhD. MD. (025-83262468 ext. +86, gezheng2008@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
complete remission rate (time frame: day 28). The study lists 2 primary outcomes in all. 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 24 Mar 2022.