Risk adapted treatment of acute myelocytic leukemia (AML).

• Register: Netherlands Trial Register
• Last refreshed on: 28 April 2013
• Main ID: NTR291
• Date of registration: 09/09/2005
• Primary sponsor: Erasmus Medical Center, Daniel den Hoed Cancer Center
• Public title: Risk adapted treatment of acute myelocytic leukemia (AML).
• Scientific title: Risk adapted treatment of acute myelocytic leukemia (AML). - HOVON 29 AML/SAKK 30/95
• Date of first enrolment: 30/3/1995
• Target sample size: 1105
• Recruitment status: complete
• URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=291
• Study type: intervention
• Study design: Randomised: Yes; Masking: None; Control: Active; Group: Parallel; Type: 2 or more arms, randomized

Countries of recruitment

The Netherlands

Contacts

• Name: B. Löwenberg

• Name: B. Löwenberg

Key inclusion & exclusion criteria

Inclusion criteria: First randomization:

1. Patients with newly diagnosed de novo AML (including all cytological subtypes M0-M7);

2. Age 15-60 yrs inclusive;

3. Patients have given informed consent;

4. Leucocytosis (WBC >30 x 109/l) is not an exclusion criterium, but it will require postponement of G-CSF administration until WBC have declined to 20 x 10^9/l on chemotherapy.





Patients after completion of CYCLE II and peripheral blood stem cell collection are eligible for second randomization if:

5. Complete remission continues (marrow cytology and blood evaluation);

6. Poor risk status according to criteria of Appendix III;

7. Not eligible for genotypically HLA matched allogeneic BMT;

8. Absence of congestive heart failure or pulmonary disease;

9. Serum bilirubin as parameter of liver function abnormalities not elevated above 3 x normal value;

10. Number of blood cells collected ("transplant"; PBSCT) being at least 2 x 108 nucleated cells/kg or 10 x 10^4 CFU-GM per kg or 2 x 10^6 CD34-positive cells per kg. In case of no or insufficient PBSCT, an adequate autologous marrow graft must have been collected;

11. Performance status of WHO grade 0, 1 or 2 at time of randomization;

12. Informed consent.
Exclusion criteria: First randomization:

1. Patients with a concurrent active malignancy, except stage I cervix carcinoma and basocellular carcinoma;

2. Patients previously treated with chemotherapy;

3. Leukemia following from a documented myelodysplasia with a duration of more than 6 months;

4. Blastic crisis of chronic myeloid leukemia or leukemia developing from myeloproliferative diseases (e.g. polycythemia vera, myelofibrosis);

5. Renal or liver function abnormalities, i.e., creatinine and bilirubin of more than 3 x normal value, except if directly attributable to the leukemia (high serum lysosymes, hyperuricemia, leukemic cell infiltration);

6. HIV positive serology;

7. Patients with severe cardiac, pulmonary or neurologic disease;

8. Pregnancy.

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Acute Myeloid Leukemia (AML)

Intervention(s)

Patients (except AML-M3 or t(15;17)) will be randomized on entry between:

Arm A:

Cycle I: idarubicin + cytarabin
Cycle II: amsacrin + cytarabin




Arm B:

Cycle I: idarubicin + cytarabin + G-CSF

Cycle II: amsacrin + cytarabin + G-CSF





Patients with AML-M3 or t(15;17) will receive arm A treatment.

Patients in CR with good risk will proceed to Cycle III: Mitoxantrone + VP-16.

Patients in CR with poor risk and a HLA matched donor will proceed to Allo BMT.

Patients in CR with poor risk without a HLA matched donor will be randomized between :

Cycle III chemotherapy and
Busulfan/Cyclophosphamide marrow ablative treatment and PBSCT.

Primary Outcome(s)

CR rate.

Secondary Outcome(s)

1. Disease-free survival;

2. Overall survival.

Secondary ID(s)

HO29

ISRCTN76815071

Source(s) of Monetary Support

Amgen, CKTO, Johnson & Johnson, Roche Nederland BV, Novartis Pharma B.V.

Secondary Sponsor(s)

VU University Medical Center, Dutch haemato-oncology association (Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)