Idarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase IV, Randomized Study to Evaluate the Safety and Efficacy of Idarubicin at Different Dosages Combined With Cytarabine as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02277847
• Other study ID #: GDREC.[2010]017
• Status: Enrolling by invitation
• Phase: Phase 4
• First received: August 25, 2014
• Last updated: October 27, 2014
• Start date: March 2010
• Est. completion date: June 2017

Study information

• Verified date: October 2014
• Source: Guangdong General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 400
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years to 60 Years

Eligibility

Inclusion Criteria:

• Age: 14~60 years old;no gender limit.

• Diagnosis: according to the diagnosis standards of AML( with the exception of M3 ) ( according to 2008 WHO diagnosis criteria of AML ).

• Performance status is not bad with Eastern Cooperative Oncology Group (ECOG) score =3.

• Research subjects must sign the informed consent documents.

Exclusion Criteria:

• Chronic myelogenous leukemia (CML) in crisis phase.

• AML transformed from other myeloproliferative diseases.

• Be accompanied with other progressing neoplasms.

• With severe malfunction of liver, lungs, kidneys or heart: the plasma levels of direct bilirubin, indirect bilirubin, alanine transaminase, aspartate transaminase and serum creatinine all are 2 times higher than normal, cardiac function is above grade II.

• With severe infection.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Idarubicin(8mg/m2) and cytosine arabinoside
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.
• Idarubicin(10mg/m2), cytosine arabinoside
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong General Hospital

References & Publications (5)

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. — View Citation

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, G — View Citation

Telek B, Rejto L, Kiss A, Batár P, Reményi G, Szász R, Ujj ZÁ, 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. Review. Hungarian. — View Citation

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 — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)	Yes
Primary	Overall survival(OS) and Disease free survival rate (DFS)		Within 5 years after randomization	Yes
Secondary	Induction remission rate		Within one month after induction therapy	Yes