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

NCT06220487 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NFEC-2023-441
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Lymphoblastic Leukemia; Philadelphia Chromosome; Philadelphia-Positive ALL; Adult ALL; IKZF1 Gene Mutation

Keywords

Olverembatinib; CD3/CD19 Bispecific T-cell Engager; Histone Deacetylase Inhibitor; Chidamide; Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia; Ph-positive

Outcome Measures

Primary Outcomes (1)

• Complete Molecular Response (CMR)

  CMR was defined as the absence of a detectable BCR::ABL1 transcript with a sensitivity of 0.01%.

  at 3 months

Secondary Outcomes (9)

• Overall survival (OS)

  at 3 and 5 years

• Event-free survival (EFS)

  at 3 and 5 years

• Adverse Events

  at 1, 3 and 5 years

• Event-free survival (EFS) of IKZF1del subgroup

  at 3 and 5 years

• Overall survival (OS) of IKZF1del subgroup

  at 3 and 5 years

Study Arms (1)

ABC protocol

EXPERIMENTAL

Adult patients with Ph-positive ALL eligble for this study will begin treatment with ABC protocol, as (A) olverembAtinib, (B) Blinatumomab and (C) Chidamide after pre-treatment with glucocorticoid, including induction and consolidation therapy for one year, and subsequent maintenance therapy for three years.

Drug: Prednisone, Olverembatinib, Blinatumomab, Chidamide

Interventions

Prednisone, Olverembatinib, Blinatumomab, Chidamide DRUG

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.

ABC protocol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent;
• Newly diagnosed adult B-precursor Ph+ ALL;
• Age greater or equal to 18 years;
• ECOG Performance Status 0-1;
• Ineligible for allo-HSCT.
• 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.
• Pancreatic function as defined below:
• Serum amylase less or equal to 1.5 x ULN Serum lipase less or equal to1.5 x ULN
• Normal cardiac function;
• Negative HIV test, negative HBV DNA and HCV RNA;
• Negative pregnancy test in women of childbearing potential.

You may not qualify if:

• 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

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Dept of Hematology, Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

RECRUITING

Related Publications (2)

• Foa R, Bassan R, Vitale A, Elia L, Piciocchi A, Puzzolo MC, Canichella M, Viero P, Ferrara F, Lunghi M, Fabbiano F, Bonifacio M, Fracchiolla N, Di Bartolomeo P, Mancino A, De Propris MS, Vignetti M, Guarini A, Rambaldi A, Chiaretti S; GIMEMA Investigators. Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults. N Engl J Med. 2020 Oct 22;383(17):1613-1623. doi: 10.1056/NEJMoa2016272.

  PMID: 33085860 BACKGROUND

• Jabbour E, Short NJ, Jain N, Huang X, Montalban-Bravo G, Banerjee P, Rezvani K, Jiang X, Kim KH, Kanagal-Shamanna R, Khoury JD, Patel K, Kadia TM, Daver N, Chien K, Alvarado Y, Garcia-Manero G, Issa GC, Haddad FG, Kwari M, Thankachan J, Delumpa R, Macaron W, Garris R, Konopleva M, Ravandi F, Kantarjian H. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2023 Jan;10(1):e24-e34. doi: 10.1016/S2352-3026(22)00319-2. Epub 2022 Nov 16.

  PMID: 36402146 BACKGROUND

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Philadelphia Chromosome

Interventions

Prednisone; olverembatinib; blinatumomab; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Translocation, Genetic; Chromosome Aberrations; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Hongsheng Zhou, M.D., Ph.D

  Department of Hematology Nanfang Hospital

  PRINCIPAL INVESTIGATOR

• Zhixiang Wang, M.D., Ph.D

  Department of Hematology Nanfang Hospital

  STUDY DIRECTOR

• Ting Zhang, M.D., Ph.D

  Department of Hematology Nanfang Hospital

  STUDY DIRECTOR

• Ren Lin, M.D., Ph.D

  Department of Hematology Nanfang Hospital

  STUDY DIRECTOR

• Congcong Wang

  Department of Hematology Nanfang Hospital

  STUDY DIRECTOR

• Jiali Yao

  Department of Hematology Nanfang Hospital

  STUDY DIRECTOR

• Qianwei Liu, Ph.D

  Department of Hematology Nanfang Hospital

  STUDY DIRECTOR

Central Study Contacts

Hongsheng Zhou, M.D; Ph.D

CONTACT

+862062787349; hanson_tcm@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2023
• First Posted: January 24, 2024
• Study Start: February 1, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 24, 2024

Record last verified: 2024-01

Locations

CN (1)