Vion Pharmaceuticals Inc. said it is moving ahead to fully enroll a pivotal Phase II study of Cloretazine in elderly acute myelogenous leukemia patients after recording at least nine responses in the first 42 patients accrued.

The trial, initiated in May and designated CLI-043, is expected to involve a total of 85 elderly patients with previously untreated de novo poor-risk AML to receive Cloretazine (VNP40101M) as a single agent. The trial population is limited to either patients over the age of 60 who have de novo AML plus one of the risk factors, such as unfavorable cytogenetics, and ECOG performance status of two or greater or a co-morbid condition that precludes them from receiving cytotoxic therapy with cytarabine and an anthracycline, or patients over the age of 70 with de novo AML who have unfavorable cytogenetics.

It's a population for which few treatment options are available, Vion's CEO Alan Kessman said in a press release. The company could not be reached for further comment.

The trial's primary endpoint is to determine to the complete response rate, while secondary endpoints will look at overall survival, disease-free survival and progression-free survival.

It is running concurrently with Vion's ongoing pivotal Phase III study of Cloretazine in combination with cytarabine in 420 patients with relapsed acute AML. That trial, which began in 2005 under a special protocol assessment with the FDA, reached the midpoint accrual of 210 patients in November, and expects interim data in March or April. The company expects full patient enrollment in the Phase III study to be completed by late this year or early 2008. (See BioWorld Today, Feb. 11, 2005.)

Competing against Vion's Cloretazine is Cambridge, Mass.-based Genzyme Corp.'s Clolar and Minneapolis-based MGI Pharma Inc.'s Dacogen. Clolar (clofarabine), a next-generation purine nucleoside analogue approved for pediatric acute lymphoblastic leukemia, is in a Phase III study in older AML patients. Dacogen (decitabine), which was approved last year to treat myelodysplastic syndromes, also is in pivotal Phase III testing in AML.

Other products in development include Xanafide, an ATP-independent tropiosomerase 2 inhibitor from Cambridge, Mass.-based Xanthus Pharmaceuticals Inc., which is in Phase II study in secondary AML patients and a Phase II-stage GVAX immunotherapy product from San Francisco-based Cell Genesys Inc.

Cloretazine is a small-molecule alkylating agent that is designed to work by damaging DNA by releasing the chloroethylating agent 90CE into the blood stream, which ultimately creates an intrastrand DNA cross-link that can kill cells. Preclinical data reported by Vion indicated that the drug had broad anticancer activity and worked even against cell lines resistant to other types of alkylating agents.

Vion also is testing the product in relapsed or refractory small-cell lung cancer.

In its preclinical pipeline, the New Haven, Conn.-based firm is evaluating a second cancer product, VNP40541, a hypoxia-selective compound, and TAPET, a modified Salmonella vector designed to delivery cancer agents directly to tumors. Vion said it is seeking development partners for TAPET.

The company's shares (NASDAQ:VION) closed at $1.53.