Trial of Donor T Cells Sensitized With Pentadecapeptides of the CMV-PP65 Protein for the Treatment of Cytomegalovirus (CMV) Infections Following Allogeneic Hematopoietic Stem Cell Transplants
|First Received Date ICMJE||May 6, 2008|
|Last Updated Date||February 3, 2016|
|Start Date ICMJE||August 2007|
|Estimated Primary Completion Date||August 2016 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||To assess the safety or toxicities of escalating doses of donor-derived CMV-pp65 peptide-specific T cells. [ Time Frame: conclusion of the study ] [ Designated as safety issue: Yes ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00674648 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||To quantitate alterations in the level of CMV antigenemia in the blood of patients with either active infection or persistent antigenemia following adoptive transfer of CMV-pp65 peptide-specific T cells. [ Time Frame: conclusion of the study ] [ Designated as safety issue: Yes ]|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Trial of Donor T Cells Sensitized With Pentadecapeptides of the CMV-PP65 Protein for the Treatment of Cytomegalovirus (CMV) Infections Following Allogeneic Hematopoietic Stem Cell Transplants|
|Official Title ICMJE||A Phase I Dose Escalation Trial of Donor T Cells Sensitized With Pentadecapeptides of the CMV-PP65 Protein for the Treatment of CMV Infections Following Allogeneic Hematopoietic Stem Cell Transplants|
The purpose of this study is to test the safety of a transfusion of specialized white cells from your transplant donor's blood, called T-cells, that have been grown and immunized against the CMV virus in the test tube. If the transplant donor is immune to CMV (ie: the donor has antibody to CMV in the blood), the T-cells will be selected and grown from the blood of the transplant donor. However, if the transplant donor is not immune to CMV, or if T-cells from the donor are not readily available, CMV-immune T-cells grown from the blood of another normal donor who is partially matched to the patients tissue type can be used. The transplant physician will explain which of these treatments is available to the patient.
This trial is called a phase I trial because phase I trials are designed to test the safety of different doses of an experimental treatment. We want to find out what effects, good and/or bad, a dose/doses of these immune T-cells will have on the patient and on the CMV infection.
Specifically, we wish to test CMV immune T-cells grown from your blood using a new method developed at our center. In this method, fragments of an important CMV protein, called CMVpp65, are chemically synthesized and then used to immunize T-cells in the test tube.
|Detailed Description||Not Provided|
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||Cytomegalovirus Infections|
|Intervention ICMJE||Biological: CMV-Peptide-Specific T cells
In this phase I trial, five escalating dose levels will be tested. Each dose will be administered to groups of at least 3 and up to 6 patients. Dose escalation will be based on the dose limiting toxicity (DLT) observed in each treatment group (Confer Biostatistics).
The patient groups and donors are outlined as follows: Group I will receive a single dose of 5 x 105 T cells/kg body weight/dose; Group II will receive a single dose of 1 x 106 T cells/kg/dose; and group III will receive a single dose of 2 x 106 T cells/kg/dose; group IV will receive 3 weekly doses of 1 x 106 T cells/kg/dose; group V will receive 3 weekly doses of 2 x 106 T cells/kg/dose.
|Study Arm (s)||Experimental: 1
This is a non-randomized single institution phase I dose escalation trial, designed to evaluate the toxicity and anti-viral activity of CMV-pp65 peptide-specific T cell lines, generated in vitro from CMV seropositive normal HSCT and 3rd party donors, when adoptively transferred to treat recipients of these transplants who have a CMV infection or persistent CMV antigenemia and are therefore at high risk of a life-threatening CMV infection.
Intervention: Biological: CMV-Peptide-Specific T cells
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Estimated Completion Date||August 2016|
|Estimated Primary Completion Date||August 2016 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Prior to receiving treatment, some patients may undergo diagnostic and/or other testing of their tissue, if available, to determine if their CMV infected cells are likely to respond to treatment with CMV specific T cells. Alternatively, blood samples may be required for research tests to ascertain that the CMV-specific T-cells do not contain any cells that could react against the patient. These patients will sign a separate pre-treatment consent. If it is determined that a patient will qualify for and might benefit from infusions of CMV CTLs, he/she will go on to sign the standard treatment consent for MSKCC IRB # 05-065 and be enrolled and treated on trial, if all other eligibility criteria are met.
However, to be eligible, the patients should meet the following clinical criteria:
Donor Eligibility for Donation of Blood Lymphocytes for Generation of
Donor-Derived CMV-Specific T cells:
Adequate health for donation as determined by institutional (related donor) or NMDP (unrelated donor) guidelines. Normal donors will be evaluated for evidence of prior sensitization to CMV by CMV serology. They will also be typed for HLA A, B, C and DR. For allogeneic hematopoietic progenitor cell transplant (HSCT) recipients, the marrow transplant donor will constitute the donor of choice, since those T-cells will grow and persist in a patient who has already engrafted with a transplant from that donor. However, if the HSCT donor is CMV seronegative or not available (e.g. a cord blood transplant or an unrelated donor who has not already donated T-cells for adoptive therapy), CMV-specific T-cells generated from a seropositive donor matched for at least 2 HLA alleles shared by the patient may be used.
Normal donors fulfilling these criteria who consent to donate blood for the generation of CMV-specific T-cells for adoptive therapeutic purposes will receive a detailed clinical evaluation, including a medical history, physical examination, and serologic testing for transmissible diseases within 1 week of donation including hepBs Ag and hepatitis C antibody, HIV-1 and 2, HTLV-1 and 2, CMV (only if previously negative), VDRL, WNV, and Chagas An HIV+ donor will be rejected on medical grounds. Donors must have Hgb value > 10 gm/dl and must be capable of undergoing a single 3-6 unit leukapheresis (preferable) or a single unit of blood for T cells (for pediatric donors, no more than 5 ml/kg at any one blood draw).
A prospective donor will be informed of the purposes of this study, and its requirements. If he/she consents, the donor will be requested to provide two blood samples:
i. An initial donation of 25ml blood anticoagulated with heparin or ACD. This blood is used to establish a B cell line transformed with the B95.8 laboratory strain of EBV. This EBV+ B cell line/ (EBVBLCL) will be used as an antigen-presenting cell. When loaded with the pool of CMVpp65 pentadecapeptides, the EBVBLCL efficiently sensitize T cells from the same donors against CMV as well as EBV.
Because the establishment and testing of an EBV transformed B cell line suitable for use or as an antigen-presenting cell require 4-5 weeks of in vitro culture, it is important that this sample be obtained as early as possible for patients at risk for a CMV infection. Because patients receiving HSCT from unrelated or HLA disparate donors are particularly at risk for severe CMV infections in the first 2-3 months after transplant, this blood sample should be obtained from the donor prior to donation of the hematopoietic progenitor cell transplant whenever possible.
ii. A donation of either a single standard 2 blood volume leukapheresis collected in standard ACD anticoagulant. If it is impossible to collect a leukapheresis from some of the donors, a unit of whole blood will be acceptable. However, the AICTF (Adoptive Immune Cell Therapy Facility manufacturing the clinical grade cell products under GMP conditions in MSKCC) may only be able to generate a limited number of T cells from a unit of blood. This blood is required for isolation of the T cells to be sensitized with the pool of CMVpp65 15-mers loaded on the autologous EBVBLCL, and propagated in vitro. In addition, it is required to provide autologous feeder cells essential to sustain T-cell growth without the risk of stimulating the growth of alloreactive T-cells capable of inducing GVHD.
This donation of a leukapheresis or a unit of blood will be obtained from unrelated HSCT donors at least 2 weeks after their donation of an HSCT, or as soon as possible thereafter.
In order to limit the number of blood or leukapheresis donations that would be required of any donor, each donor will be informed of the following potential applications of the blood cells donated. The white cells contained in one leukapheresis are sufficient to grow enough T- cells to treat the three conditions below in a transplant patient:
In addition to these prospectively accrued donors, we have, since the initiation of this protocol, generated over 100 CMV-specific T-cells for patients at high risk for infection, of which far fewer patients have required treatment. Since these patients are now beyond the period of risk for CMV infection, their donors will be approached with a separate consent to allow for the use of their T cells in recipients other than the primary patients for whom they initially donated cells.
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00674648|
|Other Study ID Numbers ICMJE||05-065|
|Has Data Monitoring Committee||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||Memorial Sloan Kettering Cancer Center|
|Study Sponsor ICMJE||Memorial Sloan Kettering Cancer Center|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Memorial Sloan Kettering Cancer Center|
|Verification Date||February 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP