Unique ID issued by UMIN | UMIN000012173 |
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Receipt number | R000014230 |
Scientific Title | Phase II study of dasatinib (DA) in combination with chemotherapy and allogeneic stem cell transplantation (SCT) for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia by Japan Acute Leukemia Study Group (JALSG Ph+ALL213) |
Date of disclosure of the study information | 2013/11/01 |
Last modified on | 2022/01/30 12:52:55 |
Phase II study of dasatinib (DA) in combination with chemotherapy and allogeneic stem cell transplantation (SCT) for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia by Japan Acute Leukemia Study Group (JALSG Ph+ALL213)
Phase II study of DA in combination with chemotherapy and allogeneic SCT for newly diagnosed Ph+ALL (JALSG Ph+ALL213)
Phase II study of dasatinib (DA) in combination with chemotherapy and allogeneic stem cell transplantation (SCT) for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia by Japan Acute Leukemia Study Group (JALSG Ph+ALL213)
Phase II study of DA in combination with chemotherapy and allogeneic SCT for newly diagnosed Ph+ALL (JALSG Ph+ALL213)
Japan |
Philadelphia chromosome-positive acute lymphoblastic leukemia
Hematology and clinical oncology |
Malignancy
YES
To evaluate the efficacy and safety of DA in combination with chemotherapy and allogeneic SCT for patients with newly diagnosed Philadelphia-chromosome positive acute lymphophblastic leukemia
Safety,Efficacy
Exploratory
Explanatory
Phase II
3-year event-free survival
Key secondary endpoints are;
1. The proportion of complete hematological remission (CHR) after induction.
2. The proportion of complete molecular remission (CMR) at the following points.
(1) after intensive consolidation
(2) pre- and day30, day100 post- SCT.
3. 3-, and 5-year OS, EFS, RFS.
4. Prognostic significance of CMR at the following points.
(1) after intensive consolidation, (2) pre-SCT, (3) day30 of post-SCT, (4) day100 of post-SCT
5. The efficacy of hematopoietic SCT; day100, 1-year OS, RFS, relapse rate, non-relapse mortality.
6. Prognostic significance of additional cytogenetic abnormalities
7. The proportion of therapy related mortality
8. Analysis of early death in induction and intensive consolidation therapy.
9. The frequency of adverse events in each steps of treatment.
10. Safety of hematopoietic SCT; frequency of graft failure, acute and chronic GVHD.
Interventional
Single arm
Non-randomized
Open -no one is blinded
Historical
1
Diagnosis
Medicine |
After the 7-day PSL therapy, during which positivity of BCR-ABL fusion transcript must be proved, 4-week DA is given with 3-week PSL to achieve CHR. Then 4-week DA is given following 4 drugs (VCR,CPM,DNR,PSL) combination to aim at CMR. C1 (HDMTX/ AraC+DA) and C2 (VCR,DNR,CPM +DA) consolidation are repeated up to 4 cycles. Patient who has an adequate donor proceed to allogeneic SCT during the consolidation. Patient who has no adequate donor proceed to 12 courses of 4-week DA-based maintenance therapy.
15 | years-old | <= |
65 | years-old | > |
Male and Female
1. Acute lymphoblastic leukemia.
2. BCR/ABL positive.
3. aged >= 15 years and < 64 years.
4. Patients must not be previously treated except PSL in the prephase PSL therapy.
5. ECOG performance status of 0, 1, 2 or 3.
6. Patients must have adequate cardiac, hepatic, renal, and pulmonary functions.
7. Voluntary written consent must be given before enrollment.
1. Heart insufficiency.
2. Pulmonary fibrosis, interstitial pneumonitis.
3. Uncontrollable diabetes mellitus.
4. Grade 4 infection.
5. HIV antibody positive.
6. HBs antigen positive.
7. Concurrent disease which may exaggerate adverse events by dasatinib.
1) Pleural effusion, ascites, or other fluid retention..
2) Congenital bleeding diathesis.
3) Diseases requiring anticoagulant or anti-platelet agents.
4) Acquired bleeding diathesis..
8. Psychiatric illness.
9. Active another malignancy.
10. Female patients who are breast feeding or pregnant.
11. Patients who, in the judgment of the investigator, would be inappropriate for entry into this study.
77
1st name | Isamu |
Middle name | |
Last name | Sugiura |
Toyohashi Municipal Hospital
Division of Hematology/Oncology
441-8570
50 Hachiken-Nishi, Aotake-Cho, Toyohashi
0532-33-6111
sugiura-isamu@toyohashi-mh.jp
1st name | Isamu |
Middle name | |
Last name | Sugiura |
Toyohashi Municipal Hospital
Division of Hematology/Oncology
441-8570
50 Hachiken-Nishi, Aotake-Cho, Toyohashi
0532-33-6111
http://www.jalsg.jp
sugiura-isamu@toyohashi-mh.jp
JALSG
Ministry of Health, Labor and Welfare
Japanese Governmental office
Japan
Toyohashi Municipal Hospital
50 Hachikennishi Aotake-cho, Toyohashi, Japan
0532-33-6111
sugiura-isamu@toyohashi-mh.jp
NO
2013 | Year | 11 | Month | 01 | Day |
Unpublished
https://doi.org/10.1182/bloodadvances.2021004607
81
DA-based two-step induction in which DA was introduced instead of IM to enhance efficacy and two-step induction to minimize toxicity showed improved survival significantly in terms of the primary endpoint of 3Y-EFS. Toxicity was minimized. No one died of chemotherapy-related toxicity. However, 16% of patients died of transplanted-related toxicity. 3Y-EFS and OS for the evaluable patients were 66% and 82%, Those of patients who underwent alloHSCT in CR1 were 72% and 88%, respectively
2022 | Year | 01 | Month | 30 | Day |
Delay expected |
The results have not been published yet.
2022 | Year | 01 | Month | 25 | Day |
Median age 45 (16-64) years
Gender, male/female, n(%)
37 (47.4)/41(52.6)
ECOG PS, 0/1 44 (56.4)/29 (37.2)
2/3 4 ( 5.1)/ 1 ( 1.3)
BCR-ABL1 type, n(%)
major 17 (21.8)
minor 56 (71.8)
major+minor 5 ( 6.4)
Copy no. of BCR-ABL1(x105) med. (range)
all case 3.9 (0.21-34.0)
major 2.7 (0.86- 4.9)
minor 4.2 (0.21-34.0)
Cytogenetics, n (%)
t(9;21) only 18/77 (23.4)
additional abnormality
50/77 (64.9)
Eighty-one patients were enrolled from 46 hospitals between 1 November 2013 and 12 April 2016. Of them, 78 patients were eligible. All of them achieved complete hematological remission after induction. Fifty-eight patients, whose CRR was 75.9%, underwent allogeneic hematopoietic stem cell transplantation (HSCT) and 6 completed the protocol chemotherapy only. Fourteen patients withdrew the study. Follow up of the study was ended on 1 July 2019 to evaluate the primary end point.
Chemotherapy-related mortality was not reported during chemotherapy. Major toxicities were neutropenia and related infectious complications, such as febrile neutropenia and sepsis. Grade 4 neutropenia were noted 51.3%, 93.5%, 98.6% and 34.9% in IND, IC, C1-1, and C2-1, which caused grade 3 febrile neutropenia 6.4%, 15.6%, 69.0%, and 7.0%, respectively. Grade4 FN were reported 2.8% in C1-1. Grade 4 sepsis was reported 1.3%, 6.5%, 8.5%, and 0.0%. Grade 4 other non-hematological were 1.3%-1.4%. As DA related toxicities, grade 3 liver dysfunction were reported 12.8%, 3.9%, and 12.7%, in IND, IC, and C1-1, respectively. One patient developed severe allergic reactions. Six (10.3%) patients died in remission due to transplant-related toxicity. Grade1/2 bleeding was reported 5 and 2 patients in IN and C1-1, respectively. Three of 5 bleeding in IN were complicated with grade3/4 DIC. Grade1/2 pleural effusion was reported 2, 1, and 1 patient in IN, IC, and C1-1.
Primary Endpoint:
At the median follow-up of 4 years(2.5-5.4), the 3Y-EFS was 66.2% (90%CI, 56.4%-74.2%). The lower level of 90% CI was 56.4%, which exceeded the threshold of 45%. Thus, the treatment in this trial was determined to be effective.
none
none
Completed
2013 | Year | 09 | Month | 04 | Day |
2013 | Year | 09 | Month | 19 | Day |
2013 | Year | 11 | Month | 01 | Day |
2019 | Year | 07 | Month | 01 | Day |
2013 | Year | 10 | Month | 30 | Day |
2022 | Year | 01 | Month | 30 | Day |
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014230
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