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Study Design: Treatment, Randomized, Open Label, Parallel Assignment This study is an open randomized and controlled trial aiming at assessing the efficacy and safety of Idarubicin (IDA) at different doses of 8mg/m2 and 10mg/m2 combined with cytarabine as induction therapy for newly diagnosed Acute Myeloid Leukaemia (AML). All the recruited patients are allocated to group A ( 8mg/m2 group) or group B ( 10mg/m2) in random. It is advised that induction therapy should begain not late than 3 days after randomization. The regimens in detail can be refered in the therapy protocol.
Idarubicin is a new generation of anthracyclines with high lipophilicity and is more permeable to cytomembrane and therefore is more cytotoxic to leukemic cells. It can pass through the blood brain barrier easily. so IDA has more advantages over other anthracyclines in prolonging the overall survival for AML. The induction therapy with idarubicin and cytarabine is now the first-line induction regimen for AML. Many clinical trails have indicated that the dosage of IDA is positively correlated with its effectiveness. But in China IDA has been used in varied dosages ranging from 6 to 12 mg/m2. In most Chinese hospitals, the usual dosage range of IDA is from 6 to 8 mg/m2 which may contribute to the much lower 5-year survival rates of AML reported in Chinese medical literature than those in foreign literature. What is the suitable dosage of IDA as induction therapy for Chinese AML population with the best efficacy but the lest increase of side effects? Till now there is no retrospective, randomized and multicentered clinical trails to answer this question on remission-inducing dosages of IDA. All the existing trials till now are just small- sampled , single-centered , retrospective and non-randomized which can not provide strong evidences .
This study aims at comparing two induction doses of 8mg/m2 and 10mg/m2 of IDA with the method of prospective randomized and multi-centered trial.The two doses of IDA have been used in many Chinese hospitals for many years, its effectiveness and safety have been recognized. This trail aims at the and side effects of IDA during induction therapy and its effect on the long-term survival of Chinese AML population, so it can provide strong evidences for optimal dosage of IDA for Chinese AML population.It can not only reduce the waste of medical social resources but also produce good social and economic benefits.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IDA 8mg/M2 | Experimental | IDA 8mg/M2 per day, D1-3. iv injection in 10 minutes;Ara-C:100-200mg/M2 per day, D1-7. administration advice: at first, 25 mg/M2 of Ara-C is given by fast intravenous injection, then 100 mg/M2 of Ara-C is given by continuous iv drip for 24 hours for successive 7 days. |
|
| IDA 10mg/M2 | Active Comparator | IDA 10mg/M2 per day, D1-3. iv. injection in 10mimutes;Ara-C:100-200mg/M2 per day, D1-7. administration advice: at first, 25 mg/M2 of Ara-C is given by fast intravenous injection, then 100 mg/M2 of Ara-C is given by continuous iv drip for 24 hours for successive 7 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Idarubicin(8mg/m2) and cytosine arabinoside | Drug | IDA 8mg/M2 per day, D1-3. iv injection in 10 minutes;Ara-C:100-200mg/M2 per day, D1-7. administration advice: at first, 25 mg/M2 of Ara-C is given by fast intravenous injection, then 100 mg/M2 of Ara-C is given by continuous iv drip for 24 hours for successive 7 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival(OS) and Disease free survival rate (DFS) | Within 5 years after randomization |
| Measure | Description | Time Frame |
|---|---|---|
| Induction remission rate | Within one month after induction therapy |
| Measure | Description | Time Frame |
|---|---|---|
| safety assessment (infection rate during induction therapy, liver and kidney toxicity, therapy related mortality, recovery time of blood count) | Randomization until death or two years post last subject last treatment visit (or clinical cutoff) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Xin Du, MD.PhD | Guangdong Provincial People's Hospital | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18398750 | Result | Yamashita T, Fukushima T, Ueda T. Pharmacokinetic self-potentiation of idarubicin by induction of anthracycline carbonyl reducing enzymes. Leuk Lymphoma. 2008 Apr;49(4):809-14. doi: 10.1080/10428190801947526. | |
| 12627513 | Result | Tsimberidou A, Estey E, Cortes J, Thomas D, Faderl S, Verstovsek S, Garcia-Manero G, Keating M, Albitar M, O'Brien S, Kantarjian H, Giles F. Gemtuzumab, fludarabine, cytarabine, and cyclosporine in patients with newly diagnosed acute myelogenous leukemia or high-risk myelodysplastic syndromes. Cancer. 2003 Mar 15;97(6):1481-7. doi: 10.1002/cncr.11239. |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D015255 | Idarubicin |
| D003561 | Cytarabine |
| D012449 | Safety |
| ID | Term |
|---|---|
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
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| Idarubicin(10mg/m2), cytosine arabinoside | Drug | IDA 10mg/M2 per day, D1-3. iv. injection in 10mimutes;Ara-C:100-200mg/M2 per day, D1-7. administration advice: at first, 25 mg/M2 of Ara-C is given by fast intravenous injection, then 100 mg/M2 of Ara-C is given by continuous iv drip for 24 hours for successive 7 days. |
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| 16197446 | Result | Russo D, Malagola M, de Vivo A, Fiacchini M, Martinelli G, Piccaluga PP, Damiani D, Candoni A, Michielutti A, Castelli M, Testoni N, Ottaviani E, Rondoni M, Pricolo G, Mazza P, Zuffa E, Zaccaria A, Raspadori D, Bocchia M, Lauria F, Bonini A, Avanzini P, Gugliotta L, Visani G, Fanin R, Baccarani M. Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients. Br J Haematol. 2005 Oct;131(2):172-9. doi: 10.1111/j.1365-2141.2005.05745.x. |
| 22512017 | Result | Chaleff S, Hurwitz CA, Chang M, Dahl G, Alonzo TA, Weinstein H. Phase II study of 2-chlorodeoxyadenosine plus idarubicin for children with acute myeloid leukaemia in first relapse: a paediatric oncology group study. Br J Haematol. 2012 Mar;156(5):649-55. doi: 10.1111/j.1365-2141.2011.08976.x. |
| 22318524 | Result | Telek B, Rejto L, Kiss A, Batar P, Remenyi G, Szasz R, Ujj ZA, Udvardy M. [Current treatment of acute myeloid leukaemia in adults]. Orv Hetil. 2012 Feb 19;153(7):243-9. doi: 10.1556/OH.2012.29304. Hungarian. |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D000056 | Accident Prevention |
| D000059 | Accidents |
| D011634 | Public Health |
| D004778 | Environment and Public Health |