Phase I trial in Acute Myeloid Leukemia (IPH 2101-101 and IPH 2101-102)

IPH 2101-101 was a Phase I trial evaluating the safety, tolerability and pharmacological profile of single dose IPH 2101 in elderly AML patients in complete remission after first induction and consolidation treatment. The trial featured a dose-escalation protocol with seven dose levels (from 0.0003 to 3 mg/kg with 3 patients per dose level). The objective was to determine a safe and pharmacologically active dose. Patients from the Phase I trial who have not relapsed at the end of their treatment cycle can enter an extension study with repeated administrations (IPH 2101-102).

Twenty-three patients were enrolled in the study. Data revealed good tolerance at all tested doses of IPH 2101, with rare, transient and moderate adverse events. Drug-related adverse events were mostly fever, rash and pruritus. The Maximum Tolerated Dose has not been reached.

A clear relationship between dose/ blood concentration/ receptor occupancy was observed, in accordance with preclinical models and with low inter-patient variability. The full receptor occupancy objective was met.

These results were reported in an oral presentation by Dr. Vey (MD, Institut Paoli Calmettes, Marseille), lead investigator of the trial, at the 2009 ASH meeting.

IPH 2101-102 has been extended with an additional cohort of 12 patients who will receive repeated administration of IPH 2101 at a dose of 1mg/kg dose. The objective of this trial extension is to confirm on a larger AML patient population the safety and the pharmacodynamic properties of repeated doses of IPH 2101. The trial could also provide activity data on remission duration.
 

About acute myeloid leukemia (“AML”)

Acute myeloid leukemia is one of the most common types of leukemia in adults in the United States and Europe. 13,290 new cases of AML were diagnosed in the United States in 2008, accounting for less than 1% of all cancers but more than 30% of all leukemias (source: American Cancer Society). The incidence of AML is low below the age of 40 but increases progressively with age, from approximately 1 per 100,000 at 40 to more than 15 per 100,000 at 75 and over. Most patients are diagnosed with AML after the age of 65 (Source: SEER Cancer Statistics Review, 2003).

In elderly patients, the prognosis for AML is very unfavorable, with a 5-year survival rate of about 5%. Although the complete treatment response rate is 50 to 60%, most patients relapse rapidly.
At present, the usual induction therapy (aimed at reducing the leukemic cell burden) is chemotherapy. One of the post-remission therapies is stem cell transplantation.

Successful treatment is far less frequent in elderly AML patients than in younger patients. Therefore, there is a need for an efficient drug with a better safety profile than existing AML treatment regimens - especially for elderly patients.