Safety Study of IL-7 in Recipients of a Hemopoietic Stem Cell Transplant Peripheral Blood Stem Cell Transplant
|ClinicalTrials.gov Identifier: NCT00684008|
Recruitment Status : Completed
First Posted : May 26, 2008
Last Update Posted : July 26, 2012
This is a phase I inter-patient dose escalation open labeled study assessing multiple doses of CYT107 in patients of at least 15 years of age, who are recipients of HLA matched ex vivo T cell depleted bone marrow or peripheral blood stem transplants.
The dose escalation design is aimed at establishing the absence of significant toxicity and to define a biologically active dose in this patient population.
At each dose level, eligible patients will receive 3 doses of CYT107 injected subcutaneously (under the skin of the arm, legs, or stomach) once a week for 3 weeks.
Groups of three patients will be entered at each dose level of CYT107. Three dose levels are planned: 10 mcg/kg/week, 20 mcg/kg/week and 30 mcg/kg/week. Three patients must complete day 42 of the study at a dose level without a dose limiting toxicity (DLT) before there is escalation to the next dose level.
|Condition or disease||Intervention/treatment||Phase|
|AML CML MDS||Drug: CYT107 - Recombinant glycosylated human interleukin 7. Drug: rhIL-7 (CYT107)||Phase 1|
Rationale: Delayed and deficient reconstitution of T cells and their functions are a major obstacle to the success of a hematopoietic stem cell transplant (HSCT). CYT-107 may have potential clinical use after allogeneic HSCT to enhance lymphoid reconstitution which could have a number of beneficial effects including decreased morbidity and mortality from post-transplant infections. Our preliminary data with a previous generation IL-7, CYT 99 007, raise the possibility that IL-7 could have, in some cases, an anti-GVHD effect while keeping the anti-tumor effect of the allograft intact.
- To determine the safety and a recommended dose of CYT107 (r-hIL-7) in recipients of an HLA-matched related or unrelated ex vivo T-cell-depleted bone marrow (BM) or peripheral blood stem cell (PBSC) transplant after initial engraftment and hematopoietic reconstitution.
- If toxicities are encountered, to establish the maximum tolerated dose (MTD) and dose limiting toxicities (DLT).
- To define the pharmacokinetics of escalating doses of CYT107 in recipients of allogeneic transplants.
To achieve preliminary characterization:
- Of the effects of CYT107 treatment on engraftment and GVHD.
- Of the effects of CYT107 on the recovery of T, NK and B cell populations and their functions in vitro.
- Of a tolerable biologically active range of doses for CYT107 in recipients of allogeneic transplants.
- Whether and to what degree administration of CYT107 might influence the risk of developing an EBV-lymphoproliferative disorder.
- Of the effects of CYT107 treatment on leukemia relapse.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official 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|
|Study Start Date :||March 2008|
|Study Completion Date :||April 2011|
Single arm dose escalation study. Three successive cohorts of 3 patients each. Doses to be evaluated: 10, 20, and 30 mcg/kg/dose for 3 consecutive doses.
CYT107 is a recombinant protein belonging to the class of growth factors known as cytokines.
CYT107 is a heavily glycosylated and sialylated form of recombinant human Interleukin-7.
CYT107 is supplied as a sterile colorless liquid at a concentration of 4 mg/ml.
Drug: CYT107 - Recombinant glycosylated human interleukin 7.
Patients will be treated with CYT107 60 to 210 days post transplantation, in 3 successive cohorts of 3 patients. Escalating doses of CYT107 will be given to successive cohorts. Patients will receive 1 dose of CYT107 by the subcutaneous route, once a week for 3 weeks. Dose level 1: 10 mcg/kg/dose for 3 doses; Dose level II: 20 mcg/kg/dose for 3 doses; Dose level III: 30 mcg/kg/dose for 3 doses. Only 1 treatment course for this initial study.
Other Name: rhIL-7Drug: rhIL-7 (CYT107)
10, 20, or 30 mcg/kg once a week for 3 consecutive weeks via the subcutaneous route.
Other Name: interleukin-7
- Toxicity of CYT107 in post-transplant patients with AML, CML and MDS using the NCI Common Toxicity Criteria version 3.0 with the BMT specific adverse event grading system. [ Time Frame: Visits: 2 week screening period; treatment visits on days 0, 7, and 14; non-treatment visits on Days 1, 21, 28, 42, 56, and 77. ]
- Pharmacokinetics and Pharmacodynamics [ Time Frame: Study days 0, 1, 7, 14, 21, 28, 42, and 77. ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00684008
|United States, New York|
|Memorial Sloan-Kettering Cancer Institute|
|New York, New York, United States, 10065|
|Principal Investigator:||Marcel van den Brink, MD, PhD||Memorial Sloan Kettering Cancer Center|