Trial Number: CLI-107-04
Title: A Phase I Study of Subcutaneous “Cyt107” (Glycosylated Recombinant Human Interleukin-7) in Patients with Refractory Metastatic Melanoma or Advanced Renal Cell Carcinoma
Countries: United States
Start Date: April 2007
Status: Ongoing
Link to Clinical Trial: Clinical Trials.Gov
About the Oncology Study
The oncology trial (CLI-107-04) targets patients with metastatic melanoma or advanced renal cell carcinoma. This dose escalation study, to include 18 to 30 patients both lymphopenic and non-lymphopenic, is being conducted at the US National Cancer Institute (NCI) in Bethesda, Maryland, in collaboration with Steven A. Rosenberg, MD, PhD, (principal investigator).
Dr. Rosenberg is Chief of Surgery at NCI and a Professor of Surgery at the Uniformed Services University of Health Sciences and at the George Washington University School of Medicine and Health Sciences in Washington, D.C. He is recognized as a pioneer in the development of immunotherapy that has resulted in the first effective immunotherapies for selected patients with advanced cancer. Most recent clinical data demonstrate how critical the immunological status of cancer patients is for their clinical outcome. CYT107 is expected to boost patient immune responses against their tumor. This will be important in the treatment of post-chemotherapy residual diseases and/or to support efficacy of various cancer vaccine approaches.
Dr. Rosenberg has previously reported (J Immunother (1997) 2006; 29(3): 313-319) the promising results of a Phase I clinical trial of Cytheris’ IL-7 in cancer patients, concluding that the study “demonstrates that IL-7 is a potent lymphopoietic factor in humans and has substantial potential for use in the treatment of patients developing lymphopenia from HIV infection or from chemotherapy used in cancer treatment. The selective increase in non–T-regulatory CD4+ T cells represents a significant advantage of the use of this cytokine”.
Trial Number: CLI-107-08
Title: A Phase I Study of CYT107 (Recombinant Glycosylated Human IL-7) in Recipients of HLA Matched Ex Vivo T cell Depleted Bone Marrow or Peripheral Blood Stem Cell Transplant
Countries: United States
Start Date: March 2008
Status: Ongoing
Link to Clinical Trial: Clinical Trials.Gov
About the Oncology Study
The primary objective of the investigation is to determine the safety and a recommended dose of CYT107 in recipients of an HLA-matched related or unrelated ex vivo T-cell-depleted bone marrow or peripheral blood stem cell transplant after initial engraftment and hematopoietic reconstitution. If toxicities are encountered, the study will also seek to establish the maximum tolerated dose (MTD) and dose limiting toxicities (DLT). The initial study site will be at the Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City, where Marcel R.M. van den Brink, M.D., Ph.D., Head, Division of Hematologic Oncology, and Miguel-Angel Perales, M.D., Assistant Attending Physician in the Bone Marrow Transplant Service, will serve as Principal Investigator and co-Principal Investigator, respectively. Additional study sites are expected to open in the United States later in 2008.
Delayed and deficient reconstitution of T-cell populations and their functions constitute a major obstacle to the success of a hematopoietic stem cell allograft. Experimental studies demonstrate that IL-7 can promote recovery of thymopoiesis, peripheral lymphoid populations and their functions in murine recipients of allogeneic hematopoietic stem cell transplantation (HSCT) without augmenting Graft versus Host Disease (GVHD). Patients admitted to the study must have histologically confirmed non-lymphoid hematological malignancy such as acute myeloid leukemia (AML), high-risk AML, chronic myeloid leukemia (CML), myelodysplastic syndrome (MDS), a history of an opportunistic infection (including but not limited to CMV viremia requiring anti-viral therapy), PCP pneumonia, mycobacterial infection, herpes zoster, or viral respiratory infection (influenza, RSV, para-influenza), and have a CD4+ T-cell count < 100 at 6 months post-transplant.
Dr. van den Brink and his colleagues have published extensively in the field of allogeneic (donor provided) blood stem cell transplantation, including two key papers on the administration of IL-7 in immune reconstitution following transplantation:
Alpdogan O, Muriglan SJ, Eng J, Willis LM, Greenberg AS, van den Brink MRM. Interleukin-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation. Journal of Clinical Investigation 2003 Oct; 112(7):1095-1107. View Abstract on Pubmed.
Alpdogan O, Schmaltz C, Muriglan SJ, Kappel BJ, Perales MA, Rotolo JA, Halm JA, Rich BE, van den Brink MRM. Administration of Interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host-disease. Blood 2001Oct 1; 98(7):2256-2265. View Abstract on Pubmed.