A Single-arm, Open-label Study of Olverembatinib, CD3/CD19 Bispecific T-cell Engager, and Chidamide in Patients With Newly Diagnosed Ph+ALL

Last updated: January 21, 2024
Sponsor: Nanfang Hospital, Southern Medical University
Overall Status: Active - Recruiting

Phase

2

Condition

Leukemia

Lymphoproliferative Disorders

Platelet Disorders

Treatment

Prednisone, Olverembatinib, Blinatumomab, Chidamide

Clinical Study ID

NCT06220487
NFEC-2023-441
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 clearanceequal 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

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 branchblock. .Use of a cardiac pacemaker.

  • ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or morecontiguous leads. .Congenital long QT syndrome. .History of or presence of significantventricular or atrial arrhythmia. .Clinically significant resting bradycardia (<50beats per minute). .QTc >450 msec on screening ECG (using the QTcF formula). .Rightbundle branch block plus left anterior hemiblock, bifascicular block. .Myocardialinfarction within 3 months prior to starting olverembatinib . .Angina pectoris.
  • Impairment of gastrointestinal (GI) function or GI disease that may significantlyalter the absorption of olverembatinib or chidamide (e.g., ulcerative diseases,uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowelresection). .History of or current autoimmune disease. .History of or current relevantCNS 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 formof contraception during participation in the study and at least 3 months thereafter ormale patients not willing to ensure effective contraception during participation inthe study and at least three months thereafter.
  • Not eigiable for this study, decided by PI

Study Design

Total Participants: 67
Treatment Group(s): 1
Primary Treatment: Prednisone, Olverembatinib, Blinatumomab, Chidamide
Phase: 2
Study Start date:
February 01, 2024
Estimated Completion Date:
January 01, 2028

Study 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.

Connect with a study center

  • Dept of Hematology, Nanfang Hospital, Southern Medical University

    Guangzhou, Guangdong 510515
    China

    Active - Recruiting

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