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Compared with patients with philadelphia chromosome-negative Acute Lymphoblastic Leukemia (Ph- ALL), patients with Ph-positive (Ph+) ALL exhibit a comparatively poor prognosis. Fortunately, significant improvements have been found in response rates, disease-free survival (DFS), and overall survival (OS) for patients with Ph+ ALL with the introduction of tyrosine kinase inhibitor (TKI) therapy to treatment regimens. Based on improvements in efficacy and tolerability, next-generation TKIs have been widely used in first-line treatment for chronic myeloid leukemia (CML). Flumatinib, a TKI with more potent binding affinity for BCR-ABL1 tyrosine kinase than imatinib, demonstrated higher rates of responses, faster and deeper responses in FESTnd trial, which suggested that flumatinib might show improved clinical efficacy for treating Ph+ ALL compared with imatinib. The investigators therefore hypothesized that the addition of flumatinib to combinatorial chemotherapy regimen would demonstrate greater efficacy compared with the prior use of imatinib in treating Ph+ ALL. This study explored the safety and efficacy of flumatinib versus imatinib when combined with multi-agent chemotherapy in patients with newly diagnosed Ph+ ALL.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| flumatinib arm | Experimental | 600 mg QD oral administration, fasting (2 hours before administration and 1 hour after administration). |
|
| imatinib arm | Active Comparator | 600 mg QD oral administration, with a meal |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Flumatinib | Drug | Flumatinib 600 mg qd will be given orally along with combination chemotherapy starting day 8 of induction chemotherapy. Flumatinib will be given continuously (if it's tolerable) for 2 years since achievement of complete remission (CR) as part of consolidation chemotherapy and maintenance therapy. Patients can receive allogeneic hematopoietic stem cell transplantation (HSCT),or patients in whom MCR was achieved within 3 months after treatment and continued until transplantation can receive autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation and maintenance chemotherapy. |
| Measure | Description | Time Frame |
|---|---|---|
| Relapse free survival | From the date of complete remission(CR) until the date of documented relapse or death due to any cause or the last follow-up day | up to 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| The rate of adverse events | The incidence and severity of neutropenia, anemia, rash, hypophosphatemia, edema, limb pain, and other adverse events. | through study completion, up to 24 months |
| The composite CR rate |
| Measure | Description | Time Frame |
|---|---|---|
| ABL kinase region mutation status at molecular relapse (MREL) and hematologic relapse (HREL) | up to 24 months | |
| The plasma and cerebrospinal fluid (CSF) level of flumatinib | up to 3 months |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Hematology & Blood Diseases Hospital | Tianjin | 300020 | China |
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| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C553360 | flumatinib |
| D000068877 | Imatinib Mesylate |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 |
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|
| Imatinib | Drug | Imatinib 600 mg qd will be given orally along with combination chemotherapy starting day 8 of induction chemotherapy. Imatinib will be given continuously (if it's tolerable) for 2 years since achievement of complete remission (CR) as part of consolidation chemotherapy and maintenance therapy. Patients can receive allogeneic hematopoietic stem cell transplantation (HSCT),or patients in whom MCR was achieved within 3 months after treatment and continued until transplantation can receive autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation and maintenance chemotherapy. |
|
Both CR and molecular CR are obtained at the end of induction
| up to 2 month |
| The complete remission (CR) rate,CRi rate and overall remission rate(ORR) | up to 2 month |
| The minimal residual disease (MRD) negative rate by Flow Cytometry (FCM) | up to 24 months |
| The molecular CR rate | up to 6 months |
| The rate of primary induction failure(PIF) | up to 6 months |
| The duration of molecular CR | up to 24 months |
| The duration of CR | up to 24 months |
| Time to treatment failure | up to 24 months |
| The cumulative recurrence rate | up to 24 months |
| The CNS recurrence rate | up to 24 months |
| Event free survival(EFS) | up to 24 months |
| Overall survival(OS) | up to 24 months |
| The rate of interruption and discontinuation due to AE | up to 24 months |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |