Lymphoblastic Leukemia, Acute, ChildhoodPhase 1NCT05495035
Study for Safety and Efficacy of Olverembatinib Combined With APG-2575 in Children With Relapsed/Refractory Ph + ALL
A Phase 1 study testing Olverembatinib, APG-2575, Dexamethasone in people with Lymphoblastic Leukemia, Acute, Childhood and Leukemia, Lymphoblastic, Acute, Philadelphia-Positive, run by Institute of Hematology & Blood Diseases Hospital, China at 4 sites in China.
Trial summary
This is an open-label, multicenter, phase 1b study, which is designed to explore the safety, efficacy and PK of olverembatinib, a third-generation tyrosine kinase inhibitor (TKI) marketed in China, in combination with APG-2575 in treating R/R Ph+ALL children, and to preliminarily establish the recommended dose of… Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Lymphoblastic Leukemia, Acute, Childhood, Leukemia, Lymphoblastic, Acute, Philadelphia-Positive, Relapsed Leukemia
- What is being tested?
- Olverembatinib, APG-2575, Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 4 sitesChina
- Study dates
- 1 Sep 2022to 1 Dec 2027
- Phase
- Phase 1
- 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 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Eligible patients must meet all of the following criteria:
- Children under 18 years of age on the day of signing the informed consent form, and able to swallow the oral drugs during the study period.
- Subjects who are diagnosed with Ph+ALL, and are resistant or intolerant to at least one TKI. If the subject has BCR-ABL1 T315I mutation, prior use of TKIs will not be considered.
- Drug resistance includes disease recurrence and refractory disease. Relapse: Presence of blasts > 5% in peripheral blood or bone marrow or presence of extramedullary disease following CR. Refractory disease: Failure to have CR or incomplete remission (CRi) at the end of induction therapy. Intolerance refers to ≥ grade 3 non-hematological toxicity or ≥ grade 4 hematological toxicity in subjects which is at least possibly related to the last TKI treatment, lasts for > 2 weeks, and leads to TKI withdrawal.
- Informed consent of parents or legal guardians should be obtained before any study activities.
- For patients >16 years of age, Karnofsky performance status score ≥ 50; for patients ≤ 16 years of age, Lansky performance status score ≥ 50.
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- Life expectancy of ≥ 3 months.
- For female patients of childbearing potential, urine β-HCG is negative.
- The following laboratory values must be met (reference ranges based on age and gender of children):
- Estimated glomerular filtration rate (eGFR) or radioisotope glomerular filtration rate (GFR) ≥70 mL/min/1.73 m2 based on Schwartz formula, or normal serum creatinine determined based on age and gender
- Serum albumin ≥ 3.0 g/dL
- Total bilirubin < 1.5 × upper limit of normal (ULN)
- ALT and AST < 5 × ULN
- Serum amylase and lipase ≤ 2 × ULN
- Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN
- Left ventricular ejection fraction of the heart is within the reference range
- Participants must meet the following criteria related to prior or current treatment:
- Patients on hydroxycarbamide for lowering cell counts: Discontinue hydroxycarbamide for at least 24 hours before initiating olverembatinib therapy
- Patients who have recurrence during cytotoxic therapy: Olverembatinib must be given at least 14 days after the last dose of chemotherapy with the following exceptions: Intrathecal (IT) chemotherapy and/or maintenance therapy, e.g., vincristine, purinethol, methotrexate, or glucocorticoids. For relapsed patients on maintenance therapy, 24-hour washout period is required.
- Hematopoietic stem cell transplantation (HSCT): Patients who relapse after HSCT are acceptable, provided that they do not have acute or chronic graft versus host disease (GVHD) or receive GVHD prophylaxis or treatment, and use the first dose of olverembatinib at least 90 days after transplantation.
- Biological and targeted drug products: At least a 7-day washout period is required for biological products prior to the first dose of olverembatinib. If a known adverse event (AE) occurs following the discontinuation of biological products, the period must be prolonged to cover the onset time of the known AE. The specific washout period can be comprehensively determined by the investigator.
- Monoclonal antibodies: There must be at least 3 half-lives from the use of monoclonal antibodies to the first dose of olverembatinib.
- Immunotherapy: Prior to the first dose of olverembatinib, there should be at least a 30-day washout period after completing any type of immunotherapies (e.g., tumor vaccine and chimeric antigen receptor T cell [CAR-T-cell]).
- Immunosuppressive therapy: Prior to the first dose of olverembatinib, there must be at least a 14-day washout period after completing immunosuppressive therapy (including the regimen after stem cell transplantation).
- Radiotherapy: No washout period is needed for the radiotherapy of any extramedullary site excluding the central nervous system (CNS); if subjects have received whole-body irradiation or craniospinal radiation or cranial radiation, the washout period must be more than 90 days.
- Anthracyclines: Prior to the first dose of olverembatinib, a cumulative dose of anthracyclines received by subjects must be less than 400 mg/m2 of adriamycin equivalent.
- Subjects who do not use concomitant medications that may have potential drug-drug interactions with olverembatinib. Or else, at least 5-day washout period is required.
- Subjects who never used olverembatinib.
Who cannot join
- The subject who meets any of the following criteria cannot be enrolled in this study:
- Any AEs (excluding alopecia and pigmentation) that are due to other anti-tumor therapies have not recovered to CTCAE v5.0 grade 0 - 1.
- Gastrointestinal dysfunction or gastrointestinal diseases that may significantly alter absorption of study drug.
- Uncontrollable or serious cardiovascular diseases.
- Subjects with symptomatic CNS disorder (e.g., convulsion caused by CNS disorder).
- Patients who have significant bleeding unrelated to Ph+ ALL.
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- Patients who are known to have hypersensitivity to any component of the study drug.
- Patients with uncontrolled systemic infection, or there is laboratory or clinical evidence for infection with active human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or SARS-CoV-2.
- Vaccination with attenuated live vaccines within 28 days prior to study treatment.
- Patients who have any conditions that, in the opinion of the investigator, would jeopardize the patient safety or interfere with the evaluation of safety and efficacy of the study drug.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China4 sites, 4 recruiting
- Not yet recruiting
The Second Affiliated Hospital of Anhui Medical University
Hefei, Anhui
Ningling Wang, MD, +86 13721113063
- Not yet recruiting
Qilu Hospital of Shandong University
Jinan, Shandong
Xiuli Ju, MD, +86 18560086337
- Not yet recruiting
Department of Hematology/Oncology, Shanghai Jiaotong University School of Medicine Affiliated Shanghai Children's Medical Center
Shanghai
Shuhong Shen, MD, +86 18930830638
- Recruiting
Department of Pediatrics, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, 300020
Xiaofan Zhu, MD, 86-21-23909001, xfzhu@ihcams.ac.cn
Jingliao Zhang, MD
About this study
Official title: Study for Safety and Efficacy Evaluation of Olverembatinib Combined With APG-2575 in Children With Relapsed/Refractory Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (R/R Ph + ALL）
This is an open-label, multicenter, phase 1b study, which is designed to explore the safety, efficacy and PK of olverembatinib, a third-generation tyrosine kinase inhibitor (TKI) marketed in China, in combination with APG-2575 in treating R/R Ph+ALL children, and to preliminarily establish the recommended dose of olverembatinib and APG-2575 for children based on the above results.
Read the detailed description
Eligible patients will receive a 6-week core treatment after screening, including a 2-week olverembatinib monotherapy and a 4-week combination therapy with olverembatinib, APG-2575 and dexamethasone, and based on the remission of leukemia after 2, 4, and 6 weeks of treatment, these patients will either continue olverembatinib alone/in combination with APG-2575 and dexamethasone as maintenance therapy or switch to other anti-tumor therapy.
Toxicities of this study will be graded according to NCI CTCAT (Version 5.0). The investigator will interrupt, reduce or discontinue the dose of the investigational drug according to the correlation and grade of toxicities. The study drug can be resumed when the drug related toxicities resolve to grade 1 or below.
- Conditions
- Lymphoblastic Leukemia, Acute, Childhood, Leukemia, Lymphoblastic, Acute, Philadelphia-Positive, Relapsed Leukemia, Refractory Leukemia
- Being tested
- Olverembatinib, APG-2575, Dexamethasone
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olverembatinib, APG-2575, DexamethasoneDrug
- Period 1: Subjects will orally take olverembatinib 40mg adult equivalent dose alone QOD from Day 1 to Day 14 (D1 - D14) =. The investigator may start the combination therapy in advance based on medical conditions of the subjects, but not earlier than Day 5/the third dose (D5).
- Period 2: 1) Subjects will orally take olverembatinib 40mg adult equivalent dose QOD from Day 15 to Day 42 (D15 - D42)).
- Subjects will orally take APG-2575 at a ramp up 200mg/400mg/600mg adult equivalent dos QD from D13 to D42 at a dose . In addition, a 3-day dose escalation from D13 to D15 will be needed, and the designated reference dose will be reached on D15.
- Subjects will orally take dexamethasone 6 mg/m2/day, QD from D15 to D42 at 6 mg/m2/day.
| Study group | Role | What they receive |
|---|---|---|
| Olverembatinib + APG-2575 combinational therapy | Experimental | * Period 1: Olverembatinib alone period (2 weeks):
* Period 2: olverembatinib in combination with APG-2575 and dexamethasone (4 weeks): Receives: Drug: Olverembatinib, APG-2575, Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT)
DLT evaluation is defined as adverse events or laboratory abnormalities that occur within 6 weeks after investigational drug administration, are unrelated to external causes such as progressive disease, concomitant disease, and concomitant medications, including hematologic and non-hematologic adverse events (grade according to NCI CTCAE 5.0).
Measured: 42 days
Objective Response Rate (ORR)
ORR is defined by Complete Remission (CR)+ CR with incomplete marrow recovery (CRi) + Partial Remission (PR).Response will be evaluated every period till complete treatment and three months after last dose.
Measured: 132 days
Maximum plasma concentration (Cmax)
Maximum plasma concentration (Cmax) will be assessed on all participants of each dose group on the first day of olverembatinib monotherapy in period 1, and on the first and last days of olverembatinib in combination with APG-2575 in period 2 .
Measured: 42 days
Area under the plasma concentration versus time curve (AUC)
Area under the plasma concentration versus time curve (AUC) will be assessed on all participantsof each dose group on the first day of olverembatinib monotherapy in period 1, and on the first and last days of olverembatinib in combination with APG-2575 in period 2 .
Measured: 42 days
R2PD of Olverembatinib and APG-2575
To confirm the recommended doses of olverembatinib and APG-2575 in children with Ph+ ALL
Measured: 42 days
Secondary outcomes (1)
Minimal Residual Disease (MRD) negative rate
To observe the proportion of subjects with MRD negative status in bone marrow.
Measured: 132 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2022
- Study start1 Sep 2022
- Primary completion31 Dec 2026 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphoblastic Leukemia, Acute, ChildhoodStudies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xiaofan Zhu, MD, Principal investigator, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05495035
- Sponsor's protocol ID
- IIT2022016
- Status last verified
- Apr 2026
- First submitted
- 8 Aug 2022
- Last updated
- 26 Aug 2026
- 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 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study for Safety and Efficacy Evaluation of Olverembatinib Combined With APG-2575 in Children With Relapsed/Refractory Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia (R/R Ph + ALL）
- ClinicalTrials.gov ID
- NCT05495035
- Acronym / sponsor ID
- IIT2022016
- Conditions
- Lymphoblastic Leukemia, Acute, Childhood, Leukemia, Lymphoblastic, Acute, Philadelphia-Positive, Relapsed Leukemia, Refractory Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 10 Aug 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.
This is an open-label, multicenter, phase 1b study, which is designed to explore the safety, efficacy and PK of olverembatinib, a third-generation tyrosine kinase inhibitor (TKI) marketed in China, in combination with APG-2575 in treating R/R Ph+ALL children, and to preliminarily establish the recommended dose of olverembatinib and APG-2575 for children based on the above results.
Detailed description
Eligible patients will receive a 6-week core treatment after screening, including a 2-week olverembatinib monotherapy and a 4-week combination therapy with olverembatinib, APG-2575 and dexamethasone, and based on the remission of leukemia after 2, 4, and 6 weeks of treatment, these patients will either continue olverembatinib alone/in combination with APG-2575 and dexamethasone as maintenance therapy or switch to other anti-tumor therapy.
Toxicities of this study will be graded according to NCI CTCAT (Version 5.0). The investigator will interrupt, reduce or discontinue the dose of the investigational drug according to the correlation and grade of toxicities. The study drug can be resumed when the drug related toxicities resolve to grade 1 or below.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olverembatinib + APG-2575 combinational therapy | Experimental | Drug: Olverembatinib, APG-2575, Dexamethasone* Period 1: Olverembatinib alone period (2 weeks): * Period 2: olverembatinib in combination with APG-2575 and dexamethasone (4 weeks): |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (28 listed)
- Eligible patients must meet all of the following criteria:
- Drug resistance includes disease recurrence and refractory disease. Relapse: Presence of blasts > 5% in peripheral blood or bone marrow or presence of extramedullary disease following CR. Refractory disease: Failure to have CR or incomplete remission (CRi) at the end of induction therapy. Intolerance refers to ≥ grade 3 non-hematological toxicity or ≥ grade 4 hematological toxicity in subjects which is at least possibly related to the last TKI treatment, lasts for > 2 weeks, and leads to TKI withdrawal.
Key exclusion criteria (10 listed)
- The subject who meets any of the following criteria cannot be enrolled in this study:
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 |
|---|---|---|
| Olverembatinib, APG-2575, Dexamethasone* Period 1: Subjects will orally take olverembatinib 40mg adult equivalent dose alone QOD from Day 1 to Day 14 (D1 - D14) =. The investigator may start the combination therapy in advance based on medical conditions of the subjects, but not earlier than Day 5/the third dose (D5). * Period 2: 1) Subjects will orally take olverembatinib 40mg adult equivalent dose QOD from Day 15 to Day 42 (D15 - D42)). 2) Subjects will orally take APG-2575 at a ramp up 200mg/400mg/600mg adult equivalent dos QD from D13 to D42 at a dose . In addition, a 3-day dose escalation from D13 to D15 will be needed, and the designated reference dose will be reached on D15. 3) Subjects will orally take dexamethasone 6 mg/m2/day, QD from D15 to D42 at 6 mg/m2/day. | Drug | Olverembatinib + APG-2575 combinational therapy |
Primary outcome
Dose-limiting toxicity (DLT)
Time frame: 42 days
DLT evaluation is defined as adverse events or laboratory abnormalities that occur within 6 weeks after investigational drug administration, are unrelated to external causes such as progressive disease, concomitant disease, and concomitant medications, including hematologic and non-hematologic adverse events (grade according to NCI CTCAE 5.0).
Objective Response Rate (ORR)
Time frame: 132 days
ORR is defined by Complete Remission (CR)+ CR with incomplete marrow recovery (CRi) + Partial Remission (PR).Response will be evaluated every period till complete treatment and three months after last dose.
Maximum plasma concentration (Cmax)
Time frame: 42 days
Maximum plasma concentration (Cmax) will be assessed on all participants of each dose group on the first day of olverembatinib monotherapy in period 1, and on the first and last days of olverembatinib in combination with APG-2575 in period 2 .
Area under the plasma concentration versus time curve (AUC)
Time frame: 42 days
Area under the plasma concentration versus time curve (AUC) will be assessed on all participantsof each dose group on the first day of olverembatinib monotherapy in period 1, and on the first and last days of olverembatinib in combination with APG-2575 in period 2 .
R2PD of Olverembatinib and APG-2575
Time frame: 42 days
To confirm the recommended doses of olverembatinib and APG-2575 in children with Ph+ ALL
1 secondary outcome
Minimal Residual Disease (MRD) negative rate
Time frame: 132 days
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 26 Aug 2026.
- 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.
Xiaofan Zhu, MD principal investigator
Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Olverembatinib, APG-2575, Dexamethasone in people with Lymphoblastic Leukemia, Acute, Childhood and Leukemia, Lymphoblastic, Acute, Philadelphia-Positive, run by Institute of Hematology & Blood Diseases Hospital, China at 4 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 28 inclusion and 10 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 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Contact Jingliao Zhang, MD (+86 22 23909196, zhangjingliao@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity (DLT) (time frame: 42 days). The study lists 5 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 26 Aug 2026.