Cellerant Therapeutics Inc., a biotechnology company developing novel hematopoietic stem cell-based cellular and antibody therapies for blood disorders and cancer, announced the initiation of a Phase I/II clinical trial of CLT-008 in patients receiving intensive post-remission chemotherapy for high-risk leukemia or myelodysplasia. CLT-008, a first-in-class, allogeneic cell-based therapy, is under development to provide hematopoietic support following high-dose chemotherapy or radiation exposure, by shortening the time to neutrophil recovery and decreasing the risks of febrile neutropenia and infection.
The open-label, multi-center, dose escalation trial will evaluate the safety and tolerability of CLT-008 in the setting of chemotherapy-induced neutropenia in approximately 30 evaluable patients with high-risk acute myelogenous leukemia, acute lymphoblastic leukemia (ALL/AML), chronic myelogenous leukemia (CML) or myelodysplasia (MDS). The secondary objectives include efficacy-related endpoints such as time to neutrophil recovery, duration of severe neutropenia and thrombocytopenia, days of fever and incidence of infections and incidence and duration of hospitalization.
"The advancement of CLT-008 in a second clinical trial represents an important milestone for Cellerant and for patients receiving high-dose chemotherapy to treat their hematological malignancies," said Ram Mandalam, Ph.D., President and Chief Executive Officer of Cellerant Therapeutics. "These patients often suffer significant complications from the intensive chemotherapy that limit the dose of chemotherapy administered. With CLT-008, these patients could have a better chance for survival by allowing them to receive their full course of intensive chemotherapy regimen needed to treat their life-threatening cancers."
Febrile neutropenia is a significant dose-limiting toxicity of chemotherapy which requires hospitalization and treatment with broad-spectrum antibiotics. Occurrence of neutropenia typically requires dose reductions for chemotherapy regimens which can impact subsequent disease control and survival, especially in the treatment of acute leukemia and high-risk MDS, where dose-intensive, myelosuppressive induction and consolidation chemotherapy have demonstrated significant clinical benefit. Current treatment options include the administration of colony-stimulating factors to increase the production of neutrophils. However, in dose-intensive chemotherapy settings as required for more advanced-stage solid-tumor cancers and hematological malignancies, the risk and incidence of neutropenia is greater due to loss of the myeloid progenitor cells necessary to mature into neutrophils. CLT-008, a human Myeloid Progenitor Cell product, would provide the critical myeloid progenitor cellular support to rapidly produce neutrophils and to shorten the duration of severe neutropenia following such chemotherapy regimens.
Cellerant is also developing CLT-008 for the treatment of Acute Radiation Syndrome (ARS) under a United States Government contract awarded on September 1, 2010 and valued up to $153 million over five years with the Biomedical Advanced Research and Development Authority (BARDA) in the Office of the Assistant Secretary for Preparedness and Response of the Department of Health and Human Services.
In ARS applications, CLT-008 is intended to provide hematopoietic cellular support after exposure to ionizing radiation from a nuclear or radiological weapon, or from a nuclear accident. Cellerant has conducted various preclinical studies to indicate that a single administration of CLT-008 could provide effective treatment for ARS in an emergency situation, and could be administered up to five days post-exposure to radiation. CLT-008 is being developed under the U.S. Food and Drug Administration's Animal Rule for ARS. This approval pathway is available when human efficacy studies are neither ethical nor feasible and requires demonstration of efficacy in representative and well-characterized animal models along with safety and pharmacokinetic testing in human clinical trials. There is currently no FDA-approved medical countermeasure to treat ARS. If licensed by the FDA, the federal government could purchase CLT-008 for the Strategic National Stockpile under Project Bioshield. Project Bioshield is designed to accelerate the research, development, purchase and availability of effective medical countermeasures for the Strategic National Stockpile.