Onrigin™ (laromustine), formerly Cloretazine® (VNP40101M) is a novel alkylating agent that is being evaluated for the treatment of acute myeloid leukemia (AML) in a pivotal Phase 2 trial in elderly de novo poor-risk AML. In addition, three clinical trials of Onrigin™ (laromustine) are underway in: (i) elderly AML and myelodysplastic syndromes in combination with cytarabine; (ii) brain tumors in combination with temozolomide; and (iii) advanced hematologic malignancies in combination with hematopoietic cell transplantation.
Q. What is Onrigin™ (laromustine) and how does it work?
A: Onrigin™ (laromustine) is a small molecule that works by damaging DNA. Onrigin™ (laromustine) releases the DNA chloroethylating agent 90CE after entering the blood stream. 90CE chloroethylates the O6 position of guanine residues, ultimately resulting in an interstrand DNA cross-link. Interstrand DNA cross-links are difficult to repair and are toxic to cells. Onrigin™ (laromustine) demonstrated a broad spectrum of anticancer activity in preclinical studies, including activity in selected cell lines resistant to other alkylating agents such as BCNU, cyclophosphamide and melphalan. In preclinical studies, Onrigin™ (laromustine) has been combined with other anticancer agents such as cytarabine (Ara-C). In addition, Onrigin™ (laromustine) or its metabolite, has been shown to be capable of crossing the blood brain barrier in preclinical models.
Q. In what clinical trials is Onrigin™ (laromustine) being evaluated?
A: Onrigin™ (laromustine) is being evaluated for the treatment of acute myeloid leukemia (AML) in a pivotal Phase 2 trial in elderly de novo poor-risk AML. In addition, four clinical trials of Onrigin™ (laromustine) are underway in: (i) AML and myelodysplastic syndrome (MDS) in combination with cytarabine; (ii) AML and MDS in combination with standard remission-induction therapy; (iii) brain tumors in combination with temozolomide; and (iv) advanced hematologic malignancies in combination with hematopoietic cell transplantation.
Below is a table with a list of all completed, closed and ongoing Onrigin™ (laromustine) clinical trials.
|
Trial |
Indication |
Sponsor |
Commencement Date |
Status |
|
Phase III trial with standard remission-induction therapy |
AML and MDS |
Investigator |
December 2008 |
Ongoing |
|
Phase III trial in combination with Ara-C |
AML, relapsed |
Vion |
March 2005 |
Clinical hold lifted by FDA; New Phase III trial in development |
|
Phase II single agent trial |
AML, elderly poor-risk |
Vion |
May 2006 |
Ongoing |
|
Phase II single agent trial |
Small cell lung cancer |
Vion |
September 2005 |
Closed |
|
Phase II single agent trial |
Brain tumors, adult |
Investigator |
June 2004 |
Completed |
|
Phase II single agent trial |
AML and high-risk myelodysplastic syndromes, elderly; AML, relapsed |
Vion |
March 2004 |
Completed |
|
Phase I/II trial in combination with cytarabine |
Elderly AML and MDS |
Investigator |
May 2008 |
Ongoing |
|
Phase I/II trial in combination with temozolomide |
Brain tumors, adult |
Investigator |
September 2007 |
Ongoing |
|
Phase I/II single agent trial |
Chronic lymphocytic leukemia |
Vion |
July 2005 |
Closed |
|
Phase I trial in combination with stem cell transplantation |
Hematologic malignancies |
Investigator |
November 2007 |
Ongoing |
|
Phase I trial |
Brain tumors, pediatric |
Investigator |
April 2005 |
Completed |
|
Phase I trial in combination with temozolomide |
Hematologic malignancies |
Vion |
October 2004 |
Completed |
|
Phase I trial in combination with Ara-C |
Hematologic malignancies |
Vion |
July 2003 |
Completed |
|
Phase I single agent trial |
Solid tumors |
Vion |
February 2003 |
Completed |
|
Phase I single agent trial |
Hematologic malignancies |
Vion |
August 2002 |
Completed |
|
Phase I single agent trial |
Solid tumors |
Vion |
June 2001 |
Completed |