Imatinib in combination with cytarabine as compared to Imatinib alone in patients with first chronic phase chronic myeloid leukemia. A prospective randomized phase III study.

ISRCTN	ISRCTN51564734
DOI	https://doi.org/10.1186/ISRCTN51564734
Protocol serial number	HO78, NL615, NTR674
Sponsor	Dutch Haemato-oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON)
Funders	Roche Nederland BV, Dutch Cancer Society, Amgen, Johnson and Johnson-Orthobiotech, Novartis Pharma B.V.

Submission date: 07/06/2006
Registration date: 07/06/2006
Last edited: 08/01/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof J.J. Cornelissen
Scientific

Erasmus Medical Center
Daniel den Hoed Cancer Center
Department of Hematology
P.O. Box 5201
Rotterdam
3008 AE
Netherlands

Phone	+31 (0)10 4391598 or +31 (0)10 4391367
Email	j.cornelissen@erasmusmc.nl

Study information

Primary study design	Interventional
Study design	A prospective randomized, parallel group, phase III study
Secondary study design	Randomised controlled trial
Scientific title	Imatinib in combination with cytarabine as compared to Imatinib alone in patients with first chronic phase chronic myeloid leukemia. A prospective randomized phase III study.
Study acronym	HOVON 78 CML
Study objectives	The hypothesis to be tested is that the outcome in arm B is better than in arm A.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Chronic myeloid leukemia
Intervention	Patients meeting all eligibility criteria will be randomized between: Arm A: imatinib given orally at a total dose of 800 mg daily until progression Arm B: imatinib given orally at a total dose of 800 mg daily, combined with 2 successive cycles of intravenous ( i.v.) cytarabine 200 mg/m^2, at day 1-7, in cycles I and II, followed by imatinib monotherapy (800 mg daily) until progression
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Imatinib, cytarabine
Primary outcome measure(s)	Rate of major molecular response at 12 months from randomization
Key secondary outcome measure(s)	1. Rate and duration of major and complete molecular response 2. Rate and duration of major and complete cytogenetic response 3. Rate and duration of complete hematological response 4. Progression-free survival (i.e. time from registration to progression or death from any cause, whichever occurs first) 5. Overall survival measured from the time of registration. Patients still alive or lost to follow-up are censored at the date they were last known to be alive. 6. Toxicity 7. Actual dose-intensity of imatinib delivered 8. Incidence of mutations of abl-kinase domain
Completion date	08/05/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	65 Years
Sex	All
Target sample size at registration	330
Total final enrolment	109
Key inclusion criteria	1. Newly diagnosed patients with chronic myeloid leukemia (CML) in first chronic phase </= 2 months 2. Presence of Philadelphia chromosome or bcr-abl rearrangement 3. Age 18-65 years inclusive 4. World Health Organization (WHO) performance status </= 2 5. Written informed consent
Key exclusion criteria	1. CML in accelerated phase or blastic crisis as defined by the WHO criteria 2. Hepatic dysfunction (serum bilirubin >/= 2 x upper limit of normal [ULN], and/or alanine aminotransferase [ALAT] >/= 4 x ULN, and/or aspartate aminotransferase [ASAT >/= 4 x ULN) 3. Renal dysfunction (creatinine >/= 200 µmol/l or 2.3 mg/dl) 4. Severe cardiac dysfunction (New York Heart Association [NYHA] classification II-IV) 5. Severe pulmonary or neurological disease 6. Pregnant or lactating females 7. Patients with a history of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma 8. Patients known to be human immunodeficiency virus (HIV)-positive 9. Patients with active, uncontrolled infections 10. Previous treatment other than hydroxyurea for </= 2 months or imatinib for </= 1 month 11. Male and female patients of reproductive potential who are not practicing effective means of contraceptio
Date of first enrolment	08/05/2006
Date of final enrolment	08/05/2011

Locations

Countries of recruitment

Netherlands

Study participating centre

Erasmus Medical Center

Rotterdam
3008 AE
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/08/2013	08/01/2021	Yes	No
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

08/01/2021: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
3. The NTR numbers have been added.