ARMS - Rapidly Generated Multivirus-Specific CTLs for Prophylaxis & Treatment of EBV, CMV, Adenovirus, HHV6 & BK Virus
ARMS
ARMS - Administration Of Rapidly Generated Multivirus-Specific Cytotoxic T-Lymphocytes For The Prophylaxis And Treatment Of EBV, CMV, Adenovirus, HHV6, And BK Virus Infections Post Allogeneic Stem Cell Transplant
1 other identifier
interventional
21
1 country
2
Brief Summary
The subjects eligible for this trial have a type of blood cell cancer, other blood disease or a genetic disease for which they will receive a stem cell transplant. The donor of the stem cells will be either the subject's brother or sister, or another relative, or a closely matched unrelated donor. The Investigators are asking subjects to participate in this study which tests if blood cells from the subject's donor that have been grown in a special way, can prevent or be a effective treatment for early infection by five viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV), adenovirus, BK virus (BKV) and human herpes virus 6 (HHV6). The Investigators have grown T cells from the subject's stem cell donor in the laboratory in a way that will train them to recognize the viruses and control them when the T cells are given after a transplant. This treatment with specially trained T cells (also called cytotoxic T cells or "CTLs") has had activity against three of these viruses (CMV, EBV and Adenovirus) in previous studies. In this study the Investigators want to see if they increase the number of viruses that can be targeted to include BKV and HHV6 using a simple and fast approach to make the cells. The Investigators want to see if they can use a kind of white blood cell called T lymphocytes (or T cells) to prevent and treat adenovirus, CMV, EBV, BKV and HHV6 in the early stages of reactivation or infection.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Sep 2012
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 27, 2012
CompletedFirst Posted
Study publicly available on registry
April 4, 2012
CompletedStudy Start
First participant enrolled
September 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2017
CompletedResults Posted
Study results publicly available
May 30, 2019
CompletedMay 30, 2019
April 1, 2019
3.9 years
March 27, 2012
December 3, 2018
May 9, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants With a DLT
DLT is defined as acute GvHD grades III-IV within 42 days of the last dose of CTLs, # of patients with Grade 3-5 infusion-related adverse events within 30 days of the last dose of CTLs, and # of patients with Grade 4-5 non-hematological adverse events within 30 days of the last dose of CTLs. GVHD grade III-IV scoring is based on the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) GVHD scoring stamp or equivalent. Grade 3-5 infusion-related adverse events and Grade 4-5 non-hematological adverse events are graded by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.X.
42 days
Secondary Outcomes (3)
Percentage of Patients Who Have a Response in Anti-viral Activity
42 days
Percentage Change of Viral Load From Baseline to Follow-up
3 months
Median Peak Frequency of Specific T Cells Post-infusion
3 months
Study Arms (6)
Multivirus-specific T cells 5*10^6 mCTLs/m2 for Prophylaxis
EXPERIMENTALCohort 1 prophylaxis: Participants were administrated 5\*10\^6 mCTLs/m multivirusspecific T cells intravenously for prophylaxis of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant.
Multivirus-specific T cells 5*10^6 mCTLs/m2 for Treatment
EXPERIMENTALCohort 1 treatment: Participants were administrated 5\*10\^6 mCTLs/m multivirusspecific T cells intravenously for treatment of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant.
Multivirus-specific T cells 1*10^7 mCTLs/m2 for Prophylaxis
EXPERIMENTALCohort 2 prophylaxis: Participants were administrated 1\*10\^7 mCTLs/m multivirusspecific T cells intravenously for prophylaxis of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant.
Multivirus-specific T cells 1*10^7 mCTLs/m2 for Treatment
EXPERIMENTALCohort 2 treatment: Participants were administrated 1\*10\^7 mCTLs/m multivirusspecific T cells intravenously for treatment of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant.
Multivirus-specific T Cells 2*10^7 mCTLs/m2 for Prophylaxis
EXPERIMENTALCohort 3 prophylaxis: Participants were administrated 2\*10\^7 mCTLs/m multivirusspecific T cells intravenously for prophylaxis of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant.
Multivirus-specific T Cells 2*10^7 mCTLs/m2 for Treatment
EXPERIMENTALCohort 3 treatment: Participants were administrated 2\*10\^7 mCTLs/m multivirusspecific T cells intravenously for treatment of EBV, CMV, Adenovirus, HHV6 and BK virus infections post allogeneic stem cell transplant.
Interventions
The feasibility and safety of 3 different dose levels will be evaluated and will determine the maximum tolerated dose (MTD) level. Dose Level One: 5x10\^6 mCTLs/m2 There may be an option of administering 2 additional doses (at the same level the patient was receiving), 28 days after the first dose, in subjects that have a partial response after one dose or who receive other therapy that may affect the persistence or function of the infused CTL.
The feasibility and safety of 3 different dose levels will be evaluated and will determine the maximum tolerated dose (MTD) level. Dose Level Two: 1x10\^7 mCTLs/m2 There may be an option of administering 2 additional doses (at the same level the patient was receiving), 28 days after the first dose, in subjects that have a partial response after one dose or who receive other therapy that may affect the persistence or function of the infused CTL
The feasibility and safety of 3 different dose levels will be evaluated and will determine the maximum tolerated dose (MTD) level. Dose Level Three: 2x10\^7 mCTLs/m2 There may be an option of administering 2 additional doses (at the same level the patient was receiving), 28 days after the first dose, in subjects that have a partial response after one dose or who receive other therapy that may affect the persistence or function of the infused CTL
Eligibility Criteria
You may qualify if:
- Patients will be eligible following any type of allogeneic transplant to receive CTLs as prevention or for early reactivations as defined below.
- Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cells within 12 months.
- Prevention for patients at risk of CMV, adenovirus, EBV, BK virus, or HHV6 infection
- Treatment of reactivation or infection which is defined for each virus as below
- CMV- CMV antigenemia is monitored at least weekly post transplant. Reactivation is defined at CMV antigenemia with \<10 leukocytes positive or elevated PCR. If any patient develops CMV antigenemia with \>10 leukocytes positive or clinical evidence of CMV infection (defined as the demonstration of CMV by biopsy specimen from visceral sites (by culture or histology) either pre or after CTL infusions, standard treatment with Ganciclovir, and/or Foscarnet and Immunoglobulins will be initiated. Patients may receive CTLs for antigenemia or elevated PCR without visceral infection.
- Adenovirus- Adenovirus infection will be defined as the presence of adenoviral positivity as detected by PCR or culture from ONE site such as stool or blood or urine or nasopharynx.
- Adenovirus disease will be defined as the presence of adenoviral positivity as detected by culture from more than two sites such as stool or blood or urine or nasopharynx.
- In patients who meet the criteria for disease Cidofovir may be added unless the subject could not tolerate this agent due to nephrotoxicity. Patients may receive CTLs for elevated PCR in blood or stool.
- EBV- EBV-LPD is defined according to recent guidelines as proven EBV-LPD defined by biopsy or probable EBV-LPD defined as an elevated EBV DNA level associated with clinical symptoms (adenopathy or fever or masses on imaging) but without biopsy confirmation. Patients with EBV DNA reactivation only may receive CTLs on study. Patients with proven or probable EBV-LPD should also receive Rituxan
- BK virus- Patients post transplant may develop asymptomatic BKV viruria or viremia. BK reactivation will be defined as detection of elevated BK levels by PCR in blood or urine while disease will be defined as detection in multiple sites or in one site with symptoms. Cidofovir has been administered intravenously in a low dose (i.e. up to 1 mg/kg 3 times weekly, without probenecid) or a high dose (ie, 5 mg/kg per week with probenecid) to HSCT patients with BK infections but no randomized trials are available proving its clinical efficacy. In patients who meet the criteria for disease Cidofovir may be added unless the subject could not tolerate this agent due to nephrotoxicity.
- HHV6- HHV6 reactivation will be defined as detection of elevated HHV6 levels by PCR in blood while disease will be defined as detection in multiple sites or in one site with symptoms. Ganciclovir, Cidofovir, and foscarnet have variable in vitro activity against HHV-6, and may have a role in treating HHV-6-associated disease - hence one or more of these agents will be added in patients with disease.
- Treatment may be given to eligible patients with a single or multiple infections. Patients with multiple infections with one or more reactivation and one or more controlled infection are eligible to enroll.
- Clinical status at enrollment to allow tapering of steroids to less than 0.5 mg/kg/day prednisone.
- Karnofsky/Lansky score of ≥ 50
- ANC greater than 500/µL.
- +8 more criteria
You may not qualify if:
- Patients receiving ATG, or Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment.
- Patients with other uncontrolled infections. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment.
- Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- Patients who have received donor lymphocyte infusion (DLI) within 28 days.
- Patients with active acute GVHD grades II-IV.
- Active and uncontrolled relapse of malignancy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AlloVirlead
- Baylor College of Medicinecollaborator
- The Methodist Hospital Research Institutecollaborator
- Center for Cell and Gene Therapy, Baylor College of Medicinecollaborator
Study Sites (2)
Houston Methodist Hospital
Houston, Texas, 77030, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Related Publications (1)
Papadopoulou A, Gerdemann U, Katari UL, Tzannou I, Liu H, Martinez C, Leung K, Carrum G, Gee AP, Vera JF, Krance RA, Brenner MK, Rooney CM, Heslop HE, Leen AM. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med. 2014 Jun 25;6(242):242ra83. doi: 10.1126/scitranslmed.3008825.
PMID: 24964991DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Helen Heslop
- Organization
- Center for Cell and Gene Therapy
Study Officials
- PRINCIPAL INVESTIGATOR
Helen Heslop, MD
Baylor College of Medicine
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 27, 2012
First Posted
April 4, 2012
Study Start
September 1, 2012
Primary Completion
August 1, 2016
Study Completion
September 1, 2017
Last Updated
May 30, 2019
Results First Posted
May 30, 2019
Record last verified: 2019-04