Study of Efficacy and Safety of Flumatinib Combined With Chemotherapy in Ph Positive ALL
Status:
Recruiting
Trial end date:
2022-05-01
Target enrollment:
Participant gender:
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.