Trial Title:
A Single-arm, Open-label Study of Olverembatinib, CD3/CD19 Bispecific T-cell Engager, and Chidamide in Patients With Newly Diagnosed Ph+ALL
NCT ID:
NCT06220487
Condition:
Acute Lymphoblastic Leukemia
Philadelphia Chromosome
Philadelphia-Positive ALL
Adult ALL
IKZF1 Gene Mutation
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Philadelphia Chromosome
Prednisone
Blinatumomab
Conditions: Keywords:
Olverembatinib
CD3/CD19 Bispecific T-cell Engager
Histone Deacetylase Inhibitor
Chidamide
Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia
Ph-positive
Study type:
Interventional
Study phase:
Phase 2
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:
Prednisone, Olverembatinib, Blinatumomab, Chidamide
Description:
Phase One. Induction Consolidation, for 1 year. 1.1 Pretreatment ×1 cycle.
Prednisone，1mg/kg/d, from day 1 to 14;
1.2 Induction Therapy × 1 cycle. A: OlverembAtinib (at a dose of 40 mg Qod), from day 8
to 42. B: Blinatumomab (at a dose of 28 μg per day), from day 15 to 28. C: Chidamide (at
a dose of 10 mg Qod), from day 9 to 41.
1.3 Consolidation Block × 5 cycles. A: Olverembatinib (at a dose of 40 mg Qod) was
administered from day 1 to 42. B: Blinatumomab (at a dose of 28 μg perday) was
administered from day 1 to 14. C: Chidamide (at a dose of 10 mg Qod) was administered
from day 14 to 41.
Phase Two. Maintenance Therapy, for 3 years. 2.1 A: Olverembatinib (at a dose of 40 mg
Qod) was administered from day 1 to 42.
C: Chidamide (at a dose of 10 mg Qod) was administered from day 14 to 41.
Phase Three. Follow-up, for 5 years.
Arm group label:
ABC protocol
Summary:
ABC study is a phase 2, single-arm, open-label study of Olverembatinib, CD3/CD19
Bispecific T-cell Engager, and Chidamide in patients with newly diagnosed Philadelphia
Chromosome-positive acute lymphoblastic leukemia (Ph+ALL). This study combined third
generation TKI (Olverembatinib), histone deacetylase inhibitors (Chidamide) and CD3/CD19
bispecific T-cell engager (Blinatumomab) as first line regimen (ABC regimen) for Ph+ ALL.
Investigatorsaim to explore the efficacy and safety of ABC regimen. The primary endpoint
is the complete molecular remission （CMR） at 3 months, secondary endpoints are overall
survival (OS), event-free survival (EFS), adverse event (AE), IKZF1del, IKZF1plus,
IKZF1lpus/CD20 subgroup EFS/OS.
Detailed description:
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) is now a
relatively favorable-risk leukemia with the development of potent BCR::ABL1 tyrosine
kinase inhibitors (TKIs). Achievement of an early and deep complete molecular remission
(CMR) is an important end point in Ph+ ALL and identifies patients who may not need
allogeneic hematopoietic stem cell transplantation (allo-HSCT). The chemotherapy-free
D-ALBA trial of dasatinib and blinatumomab was safe and effective in patients with newly
diagnosed Ph-positive ALL and resulted in an estimated 3-year OS rate of 80% (NEJM 2020,
2022). To further improve the outcomes, the potent third-generation TKIs, ponatinib and
olverembatinib (ASH 2023, abs 1504), were added to chemotherapy or immunotherapy,
resulted in an overall CMR rate of 84%-90%, a 5-year survival rate of 73%, most patients
did not undergo allo-HSCT.
Of note, IKZF1plus subgroup still stands for high-risk for Ph+ALL and exhibit poor
outcome even in TKI plus blinatumomab, which indicate IKZF1del confers resistance to
immunotherapy. our previous study found that HDACi tucidinostat/chidamide could restore
the expression and functionality of IKZF1 in IKZF1del samples, including increased
expression of CD19 and reduced focal adhesion (Blood (2021) 138 (Supplement 1): 514.).
ABC study is a phase 2, single-arm, open-label study of Olverembatinib, CD3/CD19
Bispecific T-cell Engager, and Chidamide in patients with newly diagnosed Philadelphia
Chromosome-positive acute lymphoblastic leukemia (Ph+ALL). This study combined third
generation TKI (Olverembatinib), histone deacetylase inhibitors (Chidamide) and CD3/CD19
bispecific T-cell engager (Blinatumomab) as first line regimen (ABC regimen) for Ph+ ALL.
Investigators aim to explore the efficacy and safety of ABC regimen. The primary endpoint
is the complete molecular remission （CMR） at 3 months, secondary endpoints are overall
survival (OS), event-free survival (EFS), adverse event (AE), IKZF1del, IKZF1plus,
IKZF1lpus/CD20 subgroup EFS/OS.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed written informed consent;
2. Newly diagnosed adult B-precursor Ph+ ALL;
3. Age greater or equal to 18 years;
4. ECOG Performance Status 0-1;
5. Ineligible for allo-HSCT.
6. Renal and hepatic function as defined below:
AST (GOT), ALT (GPT), and AP <2 x upper limit of normal (ULN). Creatinine clearance
equal or greater than 50 mL/min.
7. Pancreatic function as defined below:
Serum amylase less or equal to 1.5 x ULN Serum lipase less or equal to1.5 x ULN
8. Normal cardiac function;
9. Negative HIV test, negative HBV DNA and HCV RNA;
10. Negative pregnancy test in women of childbearing potential.
Exclusion Criteria:
History of receiving systemic chemotherapy or CAR-T therapy for ALL.
Impaired cardiac function, including any one of the following:
.LVEF <45% as determined by MUGA scan or echocardiogram. .Complete left bundle branch
block. .Use of a cardiac pacemaker.
- ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more
contiguous leads. .Congenital long QT syndrome. .History of or presence of
significant ventricular or atrial arrhythmia. .Clinically significant resting
bradycardia (<50 beats per minute). .QTc >450 msec on screening ECG (using the QTcF
formula). .Right bundle branch block plus left anterior hemiblock, bifascicular
block. .Myocardial infarction within 3 months prior to starting olverembatinib .
.Angina pectoris.
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of olverembatinib or chidamide (e.g., ulcerative diseases,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
resection). .History of or current autoimmune disease. .History of or current
relevant CNS pathology. .Presence of CNS leukemia. .History of or current autoimmune
disease. .History of other malignancies. .Presence active infection.
- Nursing women or women of childbearing potential not willing to use an effective
form of contraception during participation in the study and at least 3 months
thereafter or male patients not willing to ensure effective contraception during
participation in the study and at least three months thereafter.
- Not eigiable for this study, decided by PI
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Dept of Hematology, Nanfang Hospital, Southern Medical University
Address:
City:
Guangzhou
Zip:
510515
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhixiang Wang, Dr.
Phone:
+862062787349
Email:
nuannuan.66@163.com
Start date:
February 1, 2024
Completion date:
January 1, 2028
Lead sponsor:
Agency:
Nanfang Hospital, Southern Medical University
Agency class:
Other
Source:
Nanfang Hospital, Southern Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06220487
