Study of Efficacy and Safety of Flumatinib Combined With Chemotherapy in Ph Positive ALL

NCT04375683 | Unknown Phase 3

• 1 other identifier: ZDYYGZ202003
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

Philadelphia chromosome (BCR-ABL1, Ph) is the most common genetic abnormality in acute lymphoblastic leukemia (ALL) and an independent prognostic risk factor. With the increase of age, the incidence of patients over 60 years old can reach 50%, whose 5-year overall survival rate was less than 20%. With the application of tyrosine kinase inhibitor (TKI), the prognosis of Ph positive ALL patients is greatly improved. At present, TKI combined with chemotherapy has become the first-line treatment recommended in the guideline of Ph positive ALL patients. However, with the use of imatinib, more and more patients develop drug resistant to imatinib. In addition, the clinical data showed that the MRD negative rate in patients treated with imatinib combined with hyper CVAD was only 22% three months later, which was far lower than 31% of the second generation TKI and 52% of the third generation TKI. Second generation TKI dasatinib and nilotinib can overcome most imatinib resistant kinase region mutations. However, patients with severe hemocytopenia, infection or other complications are often unable to tolerate the standard chemotherapy. In addition, due to the high cost, some patients can't afford the long-term use. Flumatinib is the first approved second generation TKI in China and a derivative of imatinib. Compared with imatinib, it introduced trifluoromethyl, substituted pyridine ring for benzene ring, and kept the direction of amide bond, which made the inhibitory effect of flumatinib on common kinase mutations significantly better than that of imatinib. In addition, compared with the second-generation TKI recommended in the first line of current guidelines, the incidence of quality of life related adverse reactions of flumatinib is lower, and no specific adverse reactions of the second-generation TKI have been reported. We plan to enroll 28 patients with Ph positive ALL. All patients are diagnosed by morphology, immunology, cytogenetics and molecular biology (MICM). According to subjects' age, we will divide them into two groups. Subjects aged 60 years or older are received flumatinib and dose-adjusted VDCP or prednisone regimen. Subjects younger than 60 years are received flumatinib and hyper-CVAD regimen. MRD are examined on the 8th, 15th and 29th day after chemotherapy. Then, MRD will be monitored in the third, 6th, 9th, 12th, 15th, 18th, 21th and 24th months after chemotherapy to evaluate the effect.

Conditions

Acute Lymphocytic Leukemia, Adult B-Cell; BCR-ABL1 Fusion Protein Expression

Keywords

Flumatinib; minimal residual disease

Outcome Measures

Primary Outcomes (2)

• complete remission rate

  blasts in bone marrow are less than 5%

  day 28

• minimal residual disease

  MRD is measured by flow cytometry and qPCR

  Change from MRD at 2 years

Secondary Outcomes (1)

• side effects

  6 months

Study Arms (1)

Ph-positive ALLs

EXPERIMENTAL

Subjects aged 60 years or older are received flumatinib and dose-adjusted VDCP or prednisone regimen. Subjects younger than 60 years are received flumatinib and hyper-CVAD regimen

Drug: Flumatinib

Interventions

Flumatinib DRUG

Flumatinib 600mg per day, taken on empty stomach

Ph-positive ALLs

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed as Ph positive ALL
• Signing informed consent voluntarily

You may not qualify if:

• Severe mental disorder
• Uncontrolled heart disease
• Be allergic to flumatinib or other research drugs
• More than 80 years old

Sponsors & Collaborators

• Zhongda Hospital: lead

Study Sites (2)

Department of Hematology, Zhongda Hospital Southeast University, Institute of Hematology Southeast University

Nanjing, Jiangsu, 210009, China

RECRUITING

Department of Hematology, Zhongda Hospital Southeast University, Institute of Hematology Southeast University

Nanjing, Jiangsu, 210009, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasm, Residual

Interventions

flumatinib

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Zheng Ge, PhD. MD.

  Zhongda Hospital

  STUDY CHAIR

Central Study Contacts

Zheng Ge, PhD. MD.

CONTACT

025-83262468; gezheng2008@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 26, 2020
• First Posted: May 5, 2020
• Study Start: March 1, 2020
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: March 24, 2022

Record last verified: 2022-03

Locations

CN (2)