Idarubicin Versus High Dose Daunorubicin in Acute Myelogenous Leukemia (AML)

2014-08-27 03:12:50 | BioPortfolio


The purpose of this non-inferiority study is to compare the effectiveness of two induction chemotherapy regimens (cytarabine plus idarubicin [AI] versus cytarabine plus high-dose daunorubicin [AD]) in AML. The effectiveness will be evaluated in terms of complete remission (CR) rate.



- For patients randomized to receive Idarubicin (Arm I, AI regimen) will be given Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 7 days (D 1-7) along with Idarubicin 12 mg/m2/day iv daily for 3 days (D 1-3).

- For patients randomized to receive Daunorubicin (Arm II, AD regimen) will be given Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 7 days (D 1-7) along with Daunorubicin 90 mg/m2/day iv daily for 3 days (D 1-3).


- Bone marrow aspiration and biopsy will be done between 14 to 21 days after start of induction chemotherapy.

- If the bone marrow is hypoplastic and contains no more than 5% blast cells, further chemotherapy will be deferred and the marrow examination will be repeated at the time of neutrophils over 1,000/mcL and platelets over 100,000/mcL in the peripheral blood for the evaluation of complete remission.

- If more than 5% blast cells persist at interim or later repeated bone marrow examination, a course of re-induction chemotherapy will be given.


-Reinduction chemotherapy

- Arm I (AI regimen) : Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 5 days (D 1-5) plus idarubicin 8 mg/m2/day iv daily for 2 days (D 1-2)

- Arm II (AD regimen) : Cytarabine 200 mg/m2/day by continuous iv infusion over 24 hours daily for 5 days (D 1-5) plus Daunorubicin 45 mg/m2/day iv daily for 2 days (D 1-2) .Reinduction chemotherapy should be delayed if there is a significant infection or other co-morbid medical condition.

- Patients who do not have a complete remission after a second course of induction chemotherapy will be removed from the study

4. POSTREMISSION CHEMOTHERAPY .The same postremission therapy will be given to the patients in both arms. .For patients with good- or intermediate-risk cytogenetic features or unknown cytogenetics (see appendix II), 4 courses of high-dose cytarabine will be given as post-remission therapy. Cytarabine 3 g/m2 will be administered in a 3-hour iv infusion every 12 hours on days 1, 3, and 5 (a total of six doses per course).

.For patients with high-risk cytogenetic features (see appendix II), 4 courses of intermediate-dose Cytarabine plus Etoposide will be given as post-remission therapy. Cytarabine 1 g/m2 will be given in a 1-hour iv infusion on days 1 to 6 (a total of six doses per course) and Etoposide 150 mg/m2/day will be administered in a 5-hour iv infusion on days 1 to 3 (a total of three doses per course).

.Sequential courses of postremission therapy will be given no sooner than every 28 days or 1 week after adequate marrow recovery.

.Postremission chemotherapy should be delayed if there is a significant infection or other co-morbid medical condition.

.One or two doses of Cytarabine can be omitted according to the attending physician's decision for the followings: .Marrow recovery requires more than 28 days.

- A confluent maculopapular eruption or drug-induced desquamation

- Photophobia or conjunctivitis unrelieved within 24 hours by ophthalmic steroid drops

- More than 4 episodes of watery diarrhea per day

- A fourfold increase in a previously normal serum aminotransferase or alkaline phosphatase level or a total bilirubin level exceeding 3.0 mg/dL .Treatment with high-dose cytarabine will be discontinued in patients with severe cerebellar ataxia, confusion, or other central nervous system signs thought to be unrelated to antiemetic medication.

5. EVALUATION DURING TREATMENT .During induction and consolidation chemotherapy: CBC with differentials (daily), chemical battery with electrolyte (twice a week), coagulation battery (once a week), chest x-ray (once a week).

.Bone marrow examination will be repeated on day 15 of induction chemotherapy (for the evaluation of hypocellular marrow) and at the time of ANC ≥ 1,000/μl and platelets ≥ 100,000/μl in the peripheral blood (for the evaluation of complete remission). Chromosomal analysis will be repeated at the time of the evaluation of complete remission.


.After the completion of postremission treatment (i.e. following consolidation chemotherapy or HCT): CBC with differentials (monthly for the first 12 months, then every 2-3 months for the next 4 years), other studies such as MRD monitoring (as indicated)


- Complete remission (CR): Bone marrow blasts < 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count > 1,000/mcL; platelet count > 100,000/mcL; independence of red cell transfusion (Döhner H et al, 2010).

- All criteria need to be fulfilled; marrow evaluation should be based on a count of 200 nucleated cells in an aspirate with spicules; if ambiguous, consider repeat exam after 5 to 7 days; flow cytometric evaluation may help to distinguish between persistent leukemia and regenerating normal marrow; a marrow biopsy should be performed in cases of dry tap, or if no spicules are obtained; no minimum duration of response required.

- CR with incomplete recovery (CRi): All CR criteria except for residual neutropenia (< 1,000/mcL) or thrombocytopenia (< 100,000/mcL).

- Cause of treatment failure

- Resistant disease (RD): Failure to achieve CR or CRi; only includes patients surviving ≥ 7 days following completion of initial treatment, with evidence of persistent leukemia by blood and/or bone marrow examination.

- Death in aplasia: Deaths occurring ≥ 7 days following completion of initial treatment while cytopenic; with an aplastic or hypoplastic bone marrow obtained within 7 days of death, without evidence of persistent leukemia.

- Death from indeterminate cause: Deaths occurring before completion of therapy, or < 7 days following its completion; or deaths occurring ≥ 7 days following completion of initial therapy with no blasts in the blood, but no bone marrow examination available.

- Relapse: Bone marrow blasts ≥ 5%; or reappearance of blasts in the blood; or development of extramedullary disease.

- In cases with low blast percentages (5-10%), a repeat marrow should be performed to confirm relapse. Appearance of new dysplastic changes should be closely monitored for emerging relapse. In a patient who has been recently treated, dysplasia or a transient increase in blasts may reflect a chemotherapy effect and recovery of hematopoiesis. Cytogenetics should be tested to distinguish true relapse from therapy-related MDS/AML.

Study Design

Allocation: Randomized, Control: Dose Comparison, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Acute Myelogenous Leukemia


Cytarabine plus Daunorubicin [Arm II (AD regimen)]


Asan Medical Center
Korea, Republic of




Cooperative Study Group A for Hematology

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:12:50-0400

Clinical Trials [2691 Associated Clinical Trials listed on BioPortfolio]

Study of Plerixafor Combined With Cytarabine and Daunorubicin in Patients With De Novo Acute Myeloid Leukemia

The purpose of this research study is to determine if Plerixafor can release cells into the blood and make them more sensitive to killing by Cytarabine and Daunorubicin, an anti-cancer dru...

Daunorubicin and Cytarabine With or Without Oblimersen in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

RATIONALE: Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may increase t...

Venetoclax in Combination With Intensive Induction and Consolidation Chemotherapy in Treatment Naïve AML

This research study is studying the combination of venetoclax and chemotherapy as a possible treatment for acute myelogenous leukemia (AML). The drugs involved in this study are: ...

A Study of Clofarabine and Cytarabine for Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)(CLASSIC I)

Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed acute lymphoblastic leukemia (ALL) who...

High Dose Daunorubicin Vs. Standard Dose Daunorubicin in Induction Treatment of AML

Determine the effects of escalated dose of daunorubicin in induction treatment of adult patients with acute myelogenous leukemia who are younger than 60 years of age.

PubMed Articles [7037 Associated PubMed Articles listed on BioPortfolio]

Final results of a randomized multicenter phase II study of alvocidib, cytarabine, and mitoxantrone versus cytarabine and daunorubicin (7 + 3) in newly diagnosed high-risk acute myeloid leukemia (AML).

CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia.

Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. ...

Improved Survival by Adding Lomustine to Conventional Chemotherapy for Elderly Patients With AML Without Unfavorable Cytogenetics: Results of the LAM-SA 2007 FILO Trial.

Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemot...

Novel benzobfurans with anti-microtubule activity upregulate expression of apoptotic genes and arrest leukemia cells in G2/M phase.

Novel derivatives of benzo[b]furan were found to be highly toxic towards human chronic myelogenous (K562), acute myelogenous (HL-60) and acute lymphoblastic (MOLT-4) leukemia cells.

RUNX1 Mutations Can Lead to Aberrant Expression of CD79a and PAX5 in Acute Myelogenous Leukemias: A Potential Diagnostic Pitfall.

RUNX1 is a crucial transcription factor for hematological stem cells and well-known for its association with acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML). Besides the transl...

Medical and Biotech [MESH] Definitions

A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)

A rare acute myeloid leukemia characterized by abnormal EOSINOPHILS in the bone marrow.

An acute myeloid leukemia in which abnormal PROMYELOCYTES predominate. It is frequently associated with DISSEMINATED INTRAVASCULAR COAGULATION.

An acute leukemia exhibiting cell features characteristic of both the myeloid and lymphoid lineages and probably arising from MULTIPOTENT STEM CELLS.

Congener of CYTARABINE that is metabolized to cytarabine and thereby maintains a more constant antineoplastic action.

More From BioPortfolio on "Idarubicin Versus High Dose Daunorubicin in Acute Myelogenous Leukemia (AML)"

Quick Search


Relevant Topics

Osteoporosis is a disease in which the bones become extremely porous, are subject to fracture, and heal slowly, occurring especially in women following menopause and often leading to curvature of the spine from vertebral collapse. Follow and track&n...

Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...

Searches Linking to this Trial