Phase 2
N=4
ARMS - Rapidly Generated Multivirus-Specific CTLs for Prophylaxis & Treatment of EBV, CMV, Adenovirus, HHV6 & BK Virus
Viral Infection
Bottom Line
View on ClinicalTrials.gov: NCT01570283 ↗Enrolled (actual)
4
Serious AEs
23.8%
Results posted
May 2019
Primary outcome: Primary: Number of Participants With a DLT — 0; 0; 0; 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Multivirus-specific T cells Dose Level 1 (Biological); Multivirus-specific T cells Dose Level 2 (Biological); Multivirus-specific T cells Dose Level 3 (Biological)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- AlloVir
- Primary completion
- Aug 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With a DLT |
0; 0; 0; 3; 4; 13 | — |
| SECONDARY Percentage of Patients Who Have a Response in Anti-viral Activity |
66.7; 100; 83.3 | — |
| SECONDARY Percentage Change of Viral Load From Baseline to Follow-up |
100; 100; 100; 99.2; 100; 100 | — |
| SECONDARY Median Peak Frequency of Specific T Cells Post-infusion |
224.0; 42.3; 271.3; 28.5; 1023.0; 884.5 | — |
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.
Eligibility Criteria
Inclusion Criteria
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 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.
- Bilirubin 8.0
- Pulse oximetry of > 90% on room air
- Available multivirus-specific CTLs
- Negative pregnancy test in female patients if applicable (childbearing potential who have received a reduced intensity conditioning regimen).
- Written informed consent and/or signed assent line from patient, parent or guardian.
Exclusion Criteria
- 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
Data sourced from ClinicalTrials.gov (NCT01570283). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.