Report of an international expanded access program of imatinib in adults with Philadelphia chromosome positive leukemias.
BACKGROUND
Imatinib is a selective inhibitor of the BCR/ABL tyrosine kinase. The remarkable initial results of the first phase I clinical trial published in 1999 prompted the rapid initiation of large phase II trials. They also generated intense media coverage and significant interest from patients and clinicians and demand for access to imatinib before marketing approval. In response, a worldwide expanded access program (EAP) for imatinib was implemented in May 2000.


METHODS
In total, 7380 patients with chronic myeloid leukemia (CML) and acute lymphoblastic leukemia failing prior therapies were enrolled in 106 centers in 34 countries.


RESULTS
Time to progression and overall survival, as well as the safety profile, were similar to those observed in published phase II studies. At the end of the program, patients benefiting from treatment were continued on imatinib therapy by transferring to national health care systems or patient assistance programs.


CONCLUSIONS
The imatinib EAP successfully provided therapy to patients with CML before marketing approval. The program provides an efficient framework for the development of global EAPs for innovative investigational anticancer agents in patients without a satisfactory therapeutic alternative.
Capdeville
R
R
Clinical Development, Novartis Oncology, Basel, Switzerland. Electronic address: renaud.capdeville@novartis.com.
Krahnke
T
T
Clinical Development, Novartis Oncology, Basel, Switzerland.
Hatfield
A
A
Clinical Development, Novartis Oncology, Basel, Switzerland.
Ford
J M
JM
Clinical Development, Novartis Oncology, Basel, Switzerland.
Van Hoomissen
I
I
PPD, Brussels, Belgium.
Gathmann
I
I
Clinical Development, Novartis Oncology, Basel, Switzerland.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D002648:Child; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007391:International Cooperation; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000628:therapy*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D016730:Program Development; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate