Phase I/II Trial of Early Infusion of Rapidly-generated Multivirus Specific T Cells (MVST) to Prevent Post Transplant Viral Infections
NCT ID: NCT02231853
Last Updated: 2019-12-17
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
TERMINATED
PHASE1
12 participants
INTERVENTIONAL
2014-09-03
2017-12-29
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The aim of this study is to determine the safety and efficacy of very early infusion of MVST directed against the four most common viruses causing complications after T-depleted SCT. GMP-grade allogeneic MVST from the stem cell donor will be generated using monocyte-derived donor dendritic cells (DCs) pulsed with overlapping peptide libraries of immunodominant antigens from CMV, EBV, Ad, and BKV and expanded in IL-7 and IL-15 followed by IL-2 for 10-14 days. A fraction of the routine donor leukapheresis for lymphocytes obtained prior to stem cell mobilization will be used to generate the MVST cells. MVST passing release criteria will be cryopreserved ready for infusion post SCT.
Eligible subjects on NHLBI protocol 13-H-0144 will receive a single early infusion of MVST within 30 days (target day +14, range 0-30 days) post SCT. Phase I safety monitoring will continue for 6 weeks. Viral reactivation (CMV, EBV, Ad, BK) will be monitored by PCR by serial blood sampling. The only antiviral prophylaxis given will be acyclovir to prevent herpes simplex and varicella zoster reactivation. Subjects with rising PCR exceeding threshold for treatment, or those with clinically overt viral disease will receive conventional antiviral treatment. Patients developing acute GVHD will receive standard treatment with systemic steroids. These patients are eligible for reinfusion of MVST when steroids are tapered.
The clinical trial is designed as a single institution, open label, non-randomized Phase I/II trial of MVST in transplant recipients, designed as 3-cohort dose escalation Phase I followed by a 20 subject extension Phase II at the maximum tolerated dose of cells. Safety will be monitored continuously for a period of 6 weeks post T cell transfer. The primary safety endpoint will be the occurrence of dose limiting toxicity, defined as the occurrence of Grade IV GVHD or any other SAE that is deemed to be at least probably or definitely related to the investigational product. The primary efficacy endpoint for the phase II will be the proportion of CMV reactivation requiring treatment at day 100 post transplant. Secondary endpoints are technical feasibility of MSVT manufacture, patterns of virus reactivation by PCR, and clinical disease from EBV, Ad, BK, day 100 non-relapse mortality.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The aim of this study is to determine the safety and efficacy of very early infusion of MVSTr cells directed against the four most common viruses causing complications after T-depleted SCT. GMP-grade allogeneic MVSTr from the stem cell donor will be generated using or peripheral blood mononuclear cells (PBMCs) pulsed with overlapping peptide libraries of immunodominant antigens from CMV, EBV, Ad, and BKV and expanded in IL-7 and IL-15 followed by IL-2 for 14 days. A fraction of the routine donor leukapheresis for lymphocytes obtained prior to stem cell mobilization will be used to generate the MVST cells. MVST passing release criteria will be cryopreserved ready for infusion post SCT.
Eligible subjects on NHLBI protocol 13-H-0144 will receive a single early infusion of MVSTr on day +7 post transplant range 0-14 days) post SCT. Phase I safety monitoring will continue for 6 weeks after infusion. Viral reactivation (CMV, EBV, Ad, BK) will be monitored by PCR by serial blood sampling. The only antiviral prophylaxis given will be acyclovir to prevent herpes simplex and varicella zoster reactivation. Subjects with rising PCR exceeding threshold for treatment, or those with clinically overt viral disease will receive conventional antiviral treatment. Patients developing acute GVHD will receive standard treatment with systemic steroids. These patients are eligible for reinfusion of MVST when steroids are tapered.
The clinical trial is designed as a single institution, open label, non-randomized Phase I trial of MVSTr in transplant recipients, designed as a single cohort Phase I study. Safety will be monitored continuously for a period of 6 weeks post MVSTr transfer. The primary safety endpoint will be the occurrence of dose limiting toxicity (DLT), defined as the occurrence of Grade IV GVHD, Grade III cytokine release syndrome (CRS), Grade III autoimmunity or any other SAE that is deemed to be at least probably or definitely related to the investigational product.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SINGLE_GROUP
PREVENTION
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
-1
1x10e4 MVST/kg infusion
MVST
MVST Infusion
1
1x10e5 MVST/kg infusion
MVST
MVST Infusion
2
5x10e5 MVST/kg infusion
MVST
MVST Infusion
3
1x10e6 MVST/kg infusion
MVST
MVST Infusion
3B
1x10e6 MVSTr/kg infusion
MVSTr
PBMCs will be collected by apheresis prior to mobilization for Hematopoietic stem cells collection, donor apheresis will be used partially to prepare DLIs per PI specification and remaining will be further processed by elutriation.
Monocytes and Lymphocytes are cryopreserved for further manufacture of MVSTr.
4
5x10e6 MVSTr/kg infusion
MVSTr
PBMCs will be collected by apheresis prior to mobilization for Hematopoietic stem cells collection, donor apheresis will be used partially to prepare DLIs per PI specification and remaining will be further processed by elutriation.
Monocytes and Lymphocytes are cryopreserved for further manufacture of MVSTr.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
MVST
MVST Infusion
MVSTr
PBMCs will be collected by apheresis prior to mobilization for Hematopoietic stem cells collection, donor apheresis will be used partially to prepare DLIs per PI specification and remaining will be further processed by elutriation.
Monocytes and Lymphocytes are cryopreserved for further manufacture of MVSTr.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patients with hematologic malignancies who have signed consent for NHLBI transplant protocol 13-H-0144.
* Susceptible to CMV reactivation post transplant (either donor or recipient need to be seropositive for CMV at any time prior to transplant).
* Ability to comprehend the investigational nature of the study and provide informed consent.
Exclusion Criteria
* DLCO adjusted for Hb and ventilation \< 50% predicted prior to SCT
* Left ventricular ejection fraction \< 40% (evaluated by ECHO) or \< 30% (evaluated by MUGA) prior to SCT
* AST/SGOT \> 10 times ULN (\>grade 3, CTCAE)
* Bilirubin \> 5 times ULN (\>grade 3, CTCAE)
* Estimated GFR \< 15 mL/min
* Receiving Ganciclovir, Foscarnet or Cidofovir
* Receiving corticosteroids at the dose equivalent to 0.5 mg/kg/day of methylprednisolone
* Evidence of active autoimmune process
18 Years
75 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Heart, Lung, and Blood Institute (NHLBI)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Minocher M Battiwalla, M.D.
Role: PRINCIPAL_INVESTIGATOR
National Heart, Lung, and Blood Institute (NHLBI)
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Gerdemann U, Keirnan JM, Katari UL, Yanagisawa R, Christin AS, Huye LE, Perna SK, Ennamuri S, Gottschalk S, Brenner MK, Heslop HE, Rooney CM, Leen AM. Rapidly generated multivirus-specific cytotoxic T lymphocytes for the prophylaxis and treatment of viral infections. Mol Ther. 2012 Aug;20(8):1622-32. doi: 10.1038/mt.2012.130. Epub 2012 Jul 17.
Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, Riddell SR. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med. 1995 Oct 19;333(16):1038-44. doi: 10.1056/NEJM199510193331603.
Blyth E, Clancy L, Simms R, Ma CK, Burgess J, Deo S, Byth K, Dubosq MC, Shaw PJ, Micklethwaite KP, Gottlieb DJ. Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation. Blood. 2013 May 2;121(18):3745-58. doi: 10.1182/blood-2012-08-448977. Epub 2013 Feb 22.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
14-H-0182
Identifier Type: -
Identifier Source: secondary_id
140182
Identifier Type: -
Identifier Source: org_study_id