Philadelphia-Positive ALLPhase 2NCT05931757
A Study of Olverembatinib Combined With Blinatumomab in the Treatment of Ph+ ALL
A Phase 2 study testing Olverembatinib in people with Philadelphia-Positive ALL, run by The First Affiliated Hospital of Soochow University at 1 site in China.
Trial summary
This is a multicenter, prospective, phase II study for adult de novo Philadelphia chromosome-positive acute lymphoid leukemia (Ph+ ALL) based on the combination of Olverembatinib and Blinatumomab. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Philadelphia-Positive ALL
- What is being tested?
- Olverembatinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2023to 30 Jun 2030
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or non-pregnant, non-lactating female patients who are 18 years of age or older.
- Newly diagnosed Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL, as defined by the 2016-WHO criteria. Participants should not be treated with any kind of TKIs or chemotherapy. Participants who only received preconditioning can be enrolled.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, and expected survival period ≥ 3 months.
- Organ function as indicated by the following laboratory indicators must be met:
- 1) Alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 2.5 × ULN; 2) Total bilirubin≤1.5×ULN; 3) Serum creatinine≤1.5×ULN or 24-hour calculated creatinine clearance≥50mL/min when serum creatinine >1.5×ULN; 4) Amylase≤1.5×ULN, lipase≤1.5×ULN; 5) Cardiac ejection fraction (EF) > 50%, pulmonary artery systolic blood pressure ≤ 50mmHg; 6) QT interval corrected on electrocardiogram (ECG) evaluation: QTc≤450ms in males or ≤470ms in females; 7) PT, APTT and INR≤1.5×ULN.
- 5. Willingness and ability to comply with study procedures and follow-up examination.
Who cannot join
- Human immunodeficiency virus (HIV) infection, or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCVpositive).
- Uncontrolled active infection.
- Patients who are currently suffering from active autoimmune disease or a history of autoimmune disease potentially involving the CNS.
- Patients who have any history of heart or vascular disease, such as hypertension (systolic blood pressure(HBP) > 140mmHg and/or diastolic blood pressure > 90mmHg), or take medications that are known to cause QT interval prolongation. The patients with well controlled HBP can be considered to be included.
- Cardiac ultrasonography indicates that pulmonary artery systolic blood pressure is >50 mmHg; or there are clinical symptoms related to pulmonary arterial hypertension.
- Patients who suffer from severe bleeding disorders unrelated to Ph+ ALL.
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- Patients who have any other malignant tumors that require treatment.
- Patients who have a history of pancreatitis or a history of alcohol abuse.
- Patients who have severe hypertriglyceridemia (triglyceride ≥ 5.6mmol/L).
- Patients who are pregnant, planning to become pregnant or breastfeeding.
- Patients who underwent major surgery (except for minor surgery such as catheter placement or bone marrow biopsy) within 14 days before the first drug.
- Patients who may not be able to complete all study visits or procedures required by the study protocol, including follow-up visits, and/or fail to comply with all required study procedures.
- Patients who suffer from any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the safety of the research drug.
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
First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215000
About this study
Official title: A Multicenter, Prospective Clinical Study of Olverembatinib Combined With Blinatumomab in the Treatment of Adult de Novo Philadelphia Chromosome Positive Acute Lymphoid Leukemia
This is a multicenter, prospective, phase II study for adult de novo Philadelphia chromosome-positive acute lymphoid leukemia (Ph+ ALL) based on the combination of Olverembatinib and Blinatumomab. Olverembatinib will be taken 40mg qod from the time of diagnosis, and Blinatumomab will be given intravenously up to five cycles.
Read the detailed description
This is a prospective, multicenter, one-arm phase II clinical study, aimed for evaluating the effectiveness and safety of Olverembatinib combined with Blinatumomab in the treatment of newly diagnosed adult Ph + ALL patients.
Subjects enrolled in this study will be given a 14-day induction regimen of Olverembatinib 40mg qod orally combined with blinatumomab. To prevent cytokine release syndrome (CRS), the subjects are permitted to receive pretreatment with dexamethasone combined with Olverembatinib until the leukocyte count is less than 5 × 109/L. During induction therapy, Blinatumomab will be given in an incremental dose regimen, i.e., 9 μ g/day on days 1 to 3 and 28 μ g/day was used on days 4 to 14, and then stopped for 14 days.
Olverembatinib 40mg qod combined with blinatumomab will subsequently administered as a consolidation regimen. Blinatumomab was given a fixed dose regimen during consolidation treatment, i.e. 28 μ g/day from the day 1 to the day 28, and then stopped for 14 days. A total of 3-4 cycles will be administered, with every 42 days as one cycle.
At the end of the consolidation treatment, the patient received a maintenance regimen of Olverembatinib 40mg qod orally for at least 5 years. If the patient loses molecular response (defined as BCR-ABL1/ABL1 > 0.10%) during maintenance treatment, another consolidation treatment of 3-4 cycles of blinatumomab will be initiated.
During induction and consolidation treatment, lumbar puncture combined with sheath injection will be performed three times every cycle to prevent central nervous system leukemia (CSNL). If CNSL occurs at the time of admission, patients should receive regular conventional lumbar puncture and sheath injection for treating CNSL.
During the treatment, each subject will be evaluated regularly, including hematological response, minimal residual disease (through flow cytology, FCM-MRD), cytogenetic response and molecular remission rate, as well as adverse events.
- Conditions
- Philadelphia-Positive ALL
- Being tested
- Olverembatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlverembatinibDrug
Also called Blinatumomab
Olverembatinib will be taken 40mg qod from the time of diagnosis, and Blinatumomab will be given intravenously up to five cycles.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group | Experimental | The patients would be treated with Olverembatinib, Given PO, combined with Blinatumomab, Given intravenously Receives: Drug: Olverembatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Complete Molecular Remission.
Will be estimated along with the 95% credible intervals.
Measured: From Induction through the end of three cycles of blinatumomab (approximately 16 weeks)
Secondary outcomes (5)
Percentage of Participants with CR and Incomplete Complete Remission (CRi).
Will be estimated along with the 95% credible intervals.
Measured: From Induction through the end of three cycles of blinatumomab (approximately 16 weeks)
Duration of Complete Molecular Remission.
Will be estimated along with the 95% credible intervals.
Measured: From the date of acquisition of complete molecular remission until the date of loss of complete molecular remission, assessed up to 2 to 7 years.
Event-free survival (EFS)
The Kaplan-Meier method will be used to assess EFS probabilities.
Measured: From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 2 to 7 years
Overall survival (OS)
The Kaplan-Meier method will be used to assess OS probabilities.
Measured: From the first day of treatment to time of death from any cause, assessed up 2 to 7 years.
Incidence of adverse events (AEs)
Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The proportion of patients with AEs will be estimated, along with the Bayesian 95% credible interval.
Measured: Up to approximately 2 to 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2023
- Study start1 Jul 2023 (estimated)
- Primary completion30 Jun 2025 (estimated)
- Study completion30 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Philadelphia-Positive ALLStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital of Soochow 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
- 22 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chen Suning, The First Affiliated Hospital of Soochow University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05931757
- Sponsor's protocol ID
- SZ-ALL03
- Status last verified
- Jul 2023
- First submitted
- 16 Jun 2023
- Last updated
- 5 Jul 2023
- 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 5 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Prospective Clinical Study of Olverembatinib Combined With Blinatumomab in the Treatment of Adult de Novo Philadelphia Chromosome Positive Acute Lymphoid Leukemia
- ClinicalTrials.gov ID
- NCT05931757
- Acronym / sponsor ID
- SZ-ALL03
- Conditions
- Philadelphia-Positive ALL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Soochow UniversityUniversity, hospital or other
- Study start
- 1 Jul 2023 (estimated)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 30 Jun 2030 (estimated)
- First posted
- 5 Jul 2023 (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 is a multicenter, prospective, phase II study for adult de novo Philadelphia chromosome-positive acute lymphoid leukemia (Ph+ ALL) based on the combination of Olverembatinib and Blinatumomab. Olverembatinib will be taken 40mg qod from the time of diagnosis, and Blinatumomab will be given intravenously up to five cycles.
Detailed description
This is a prospective, multicenter, one-arm phase II clinical study, aimed for evaluating the effectiveness and safety of Olverembatinib combined with Blinatumomab in the treatment of newly diagnosed adult Ph + ALL patients.
Subjects enrolled in this study will be given a 14-day induction regimen of Olverembatinib 40mg qod orally combined with blinatumomab. To prevent cytokine release syndrome (CRS), the subjects are permitted to receive pretreatment with dexamethasone combined with Olverembatinib until the leukocyte count is less than 5 × 109/L. During induction therapy, Blinatumomab will be given in an incremental dose regimen, i.e., 9 μ g/day on days 1 to 3 and 28 μ g/day was used on days 4 to 14, and then stopped for 14 days.
Olverembatinib 40mg qod combined with blinatumomab will subsequently administered as a consolidation regimen. Blinatumomab was given a fixed dose regimen during consolidation treatment, i.e. 28 μ g/day from the day 1 to the day 28, and then stopped for 14 days. A total of 3-4 cycles will be administered, with every 42 days as one cycle.
At the end of the consolidation treatment, the patient received a maintenance regimen of Olverembatinib 40mg qod orally for at least 5 years. If the patient loses molecular response (defined as BCR-ABL1/ABL1 > 0.10%) during maintenance treatment, another consolidation treatment of 3-4 cycles of blinatumomab will be initiated.
During induction and consolidation treatment, lumbar puncture combined with sheath injection will be performed three times every cycle to prevent central nervous system leukemia (CSNL). If CNSL occurs at the time of admission, patients should receive regular conventional lumbar puncture and sheath injection for treating CNSL.
During the treatment, each subject will be evaluated regularly, including hematological response, minimal residual disease (through flow cytology, FCM-MRD), cytogenetic response and molecular remission rate, as well as adverse events.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Group | Experimental | Drug: OlverembatinibThe patients would be treated with Olverembatinib, Given PO, combined with Blinatumomab, Given intravenously |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or non-pregnant, non-lactating female patients who are 18 years of age or older.
- Newly diagnosed Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL, as defined by the 2016-WHO criteria. Participants should not be treated with any kind of TKIs or chemotherapy. Participants who only received preconditioning can be enrolled.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, and expected survival period ≥ 3 months.
- Organ function as indicated by the following laboratory indicators must be met:
- 1) Alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 2.5 × ULN; 2) Total bilirubin≤1.5×ULN; 3) Serum creatinine≤1.5×ULN or 24-hour calculated creatinine clearance≥50mL/min when serum creatinine >1.5×ULN; 4) Amylase≤1.5×ULN, lipase≤1.5×ULN; 5) Cardiac ejection fraction (EF) > 50%, pulmonary artery systolic blood pressure ≤ 50mmHg; 6) QT interval corrected on electrocardiogram (ECG) evaluation: QTc≤450ms in males or ≤470ms in females; 7) PT, APTT and INR≤1.5×ULN.
Key exclusion criteria (13 listed)
- Human immunodeficiency virus (HIV) infection, or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCVpositive).
- Uncontrolled active infection.
- Patients who are currently suffering from active autoimmune disease or a history of autoimmune disease potentially involving the CNS.
- Patients who have any history of heart or vascular disease, such as hypertension (systolic blood pressure(HBP) > 140mmHg and/or diastolic blood pressure > 90mmHg), or take medications that are known to cause QT interval prolongation. The patients with well controlled HBP can be considered to be included.
- Cardiac ultrasonography indicates that pulmonary artery systolic blood pressure is >50 mmHg; or there are clinical symptoms related to pulmonary arterial hypertension.
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 |
|---|---|---|
| OlverembatinibAlso: BlinatumomabOlverembatinib will be taken 40mg qod from the time of diagnosis, and Blinatumomab will be given intravenously up to five cycles. | Drug | Treatment Group |
Primary outcome
Number of Participants with Complete Molecular Remission.
Time frame: From Induction through the end of three cycles of blinatumomab (approximately 16 weeks)
Will be estimated along with the 95% credible intervals.
5 secondary outcomes
Percentage of Participants with CR and Incomplete Complete Remission (CRi).
Time frame: From Induction through the end of three cycles of blinatumomab (approximately 16 weeks)
Duration of Complete Molecular Remission.
Time frame: From the date of acquisition of complete molecular remission until the date of loss of complete molecular remission, assessed up to 2 to 7 years.
Event-free survival (EFS)
Time frame: From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 2 to 7 years
Overall survival (OS)
Time frame: From the first day of treatment to time of death from any cause, assessed up 2 to 7 years.
Incidence of adverse events (AEs)
Time frame: Up to approximately 2 to 7 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 5 Jul 2023.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Olverembatinib in people with Philadelphia-Positive ALL, run by The First Affiliated Hospital of Soochow 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 6 inclusion and 13 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: opening soon, as of the sponsor's last update on 5 Jul 2023. 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 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Complete Molecular Remission. (time frame: From Induction through the end of three cycles of blinatumomab (approximately 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 5 Jul 2023.