Trial Title:
Study for Safety and Efficacy of Olverembatinib Combined With APG-2575 in Children With Relapsed/Refractory Ph + ALL
NCT ID:
NCT05495035
Condition:
Lymphoblastic Leukemia, Acute, Childhood
Leukemia, Lymphoblastic, Acute, Philadelphia-Positive
Relapsed Leukemia
Refractory Leukemia
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Dexamethasone
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Olverembatinib, APG-2575, Dexamethasone
Description:
- 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.
Arm group label:
Olverembatinib + APG-2575 combinational therapy
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 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Eligible patients must meet all of the following criteria:
1. 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.
2. 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.
3. Informed consent of parents or legal guardians should be obtained before any
study activities.
4. For patients >16 years of age, Karnofsky performance status score ≥ 50; for
patients ≤ 16 years of age, Lansky performance status score ≥ 50.
5. Life expectancy of ≥ 3 months.
6. For female patients of childbearing potential, urine β-HCG is negative.
7. The following laboratory values must be met (reference ranges based on age and
gender of children):
1. 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
2. Serum albumin ≥ 3.0 g/dL
3. Total bilirubin < 1.5 × upper limit of normal (ULN)
4. ALT and AST < 5 × ULN
5. Serum amylase and lipase ≤ 2 × ULN
6. Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤
1.5 × ULN
7. Left ventricular ejection fraction of the heart is within the reference
range
8. Participants must meet the following criteria related to prior or current
treatment:
1. Patients on hydroxycarbamide for lowering cell counts: Discontinue
hydroxycarbamide for at least 24 hours before initiating olverembatinib
therapy
2. 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.
3. 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.
4. 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.
5. Monoclonal antibodies: There must be at least 3 half-lives from the use of
monoclonal antibodies to the first dose of olverembatinib.
6. 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]).
7. 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).
8. 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.
9. 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.
10. 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.
11. Subjects who never used olverembatinib.
Exclusion Criteria:
- The subject who meets any of the following criteria cannot be enrolled in this
study:
1. Any AEs (excluding alopecia and pigmentation) that are due to other anti-tumor
therapies have not recovered to CTCAE v5.0 grade 0 - 1.
2. Gastrointestinal dysfunction or gastrointestinal diseases that may
significantly alter absorption of study drug.
3. Uncontrollable or serious cardiovascular diseases.
4. Subjects with symptomatic CNS disorder (e.g., convulsion caused by CNS
disorder).
5. Patients who have significant bleeding unrelated to Ph+ ALL.
6. Patients who are known to have hypersensitivity to any component of the study
drug.
7. 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.
8. Vaccination with attenuated live vaccines within 28 days prior to study
treatment.
9. 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.
Gender:
All
Minimum age:
1 Year
Maximum age:
18 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The Second Affiliated Hospital of Anhui Medical University
Address:
City:
Hefei
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Ningling Wang, MD
Phone:
+86 13721113063
Facility:
Name:
Qilu Hospital of Shandong University
Address:
City:
Jinan
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xiuli Ju, MD
Phone:
+86 18560086337
Facility:
Name:
Department of Pediatrics, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences
Address:
City:
Tianjin
Zip:
300020
Country:
China
Status:
Recruiting
Contact:
Last name:
Xiaofan Zhu, MD
Phone:
86-21-23909001
Email:
xfzhu@ihcams.ac.cn
Investigator:
Last name:
Jingliao Zhang, MD
Email:
Sub-Investigator
Facility:
Name:
Department of Hematology/Oncology, Shanghai Jiaotong University School of Medicine Affiliated Shanghai Children's Medical Center
Address:
City:
Shanghai
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Shuhong Shen, MD
Phone:
+86 18930830638
Start date:
September 1, 2022
Completion date:
December 1, 2024
Lead sponsor:
Agency:
Institute of Hematology & Blood Diseases Hospital, China
Agency class:
Other
Source:
Institute of Hematology & Blood Diseases Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05495035
