Cytomegalovirus Infections Clinical Trial
Official title:
Administration of Rapidly Generated Multivirus-specific Cytotoxic T-Lymphocytes for the Prophylaxis and Treatment of EBV, CMV, and Adenovirus Infection Post Allogeneic Stem Cell Transplant (VIRAGE)
Patient's on this protocol have a type of blood cell cancer, other blood disease or a
genetic disease and have received a stem cell transplant. The donor of the stem cells was
either a brother or sister, another relative, or a closely matched unrelated donor. The
patient is being asked to participate in this study which tests if blood cells from the
donor that have been grown in a special way, can prevent or be an effective treatment for
early infection by three viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV) and
adenovirus.
Adenovirus is a virus that usually causes symptoms of a common cold, but can cause serious
life-threatening infections in patients who have weak immune systems. It can affect the
lungs and cause very serious pneumonia, and can also damage the gut, liver, pancreas and
eyes.CMV can also cause serious infections in patients with weak or suppressed immune
systems. It usually affects the lungs, causing a very serious pneumonia, but it can also
affect the gut, the liver and the eyes. Approximately 2/3 of normal people harbor this virus
in their body. In healthy people CMV rarely causes any problems because the immune system
can keep it under control, but after a transplant, the risk of developing CMV disease is
much higher because the immune system is so weak. EBV is the virus that causes glandular
fever. It is also a life long infection like CMV that is normally controlled by the immune
system. When immunity is weak, the virus can become active and cause fevers, enlarged lymph
nodes and sometimes a type of cancer called lymphoma.
Investigators want to see if a kind of white blood cell called T lymphocytes (T cells)can be
used to prevent and treat adenovirus, CMV and EBV in the early stages of reactivation or
infection. T cells have been grown from the patient's stem cell donor in the laboratory in a
way that will train them to recognize the virus and control it when they are given after a
transplant. This treatment with specially trained T cells (also called CTLs) has had
activity against these viruses in previous studies and in this study investigators want to
see if they still have activity when they are made in a simpler and faster way. These
donor-derived multivirus-specific special cell lines are an investigational product not
approved by the Food and Drug Administration.
The purpose of this study is to evaluate whether donor-derived multivirus-specific special
cell lines are safe and can control three viruses: EBV, CMV and adenovirus.
Status | Completed |
Enrollment | 10 |
Est. completion date | April 2014 |
Est. primary completion date | May 2013 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | N/A and older |
Eligibility |
INCLUSION CRITERIA: Patients will be eligible following any type of allogeneic transplant to receive CTLs as prophylaxis or for early reactivations as defined below. 1. Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cells. 2. Prophylaxis for patients at risk of CMV, adenovirus or EBV infection (for Phase 2 portion only). In the phase 1 portion patients must meet criteria in 3 below. 3. Early treatment of reactivation or infection which is defined for each virus as below: 1. CMV: CMV antigenemia is monitored at least weekly post transplant. Early reactivation is defined at CMV antigenemia with less than 10 leucocytes positive. If any patient develops CMV antigenemia (with greater than 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. 2. 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. 3. 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 defined as EBV DNA levels > 1000 copies/ug may also receive CTLs on study. Patients with proven or probable EBV-LPD should also receive Rituxan 4. Early treatment may be given to eligible patients with a single or multiple infections. Patients with multiple infections with one reactivation and one controlled infection are eligible to enroll. 5. Patient with a CMV seronegative donor may only receive CTLs for a CMV reactivation in the dose escalation phase if the line has activity against CMV. 6. Clinical status at enrollment to allow tapering of steroids to less than 0.5 mg/kg/day prednisone. 7. Karnofsky/Lansky score of 50 or greater 8. ANC greater than 500/µL. 9. Bilirubin 2x upper limit normal or less 10. AST 3 x normal or less 11. Serum creatinine 2 x upper limit normal or less 12. HgB >8.0 13. Pulse oximetry of > 90% on room air 14. Available multi-virus-specific cytotoxic T lymphocytes 15. Negative pregnancy test in female patients if applicable (childbearing potential who have received a reduced intensity conditioning regimen). 16. Written informed consent and/or signed assent line from patient, parent or guardian. DONOR ELIGIBILITY: The donor for the CTL product will be the same donor who donated the allogeneic product for the patient's transplant. These donors for allogeneic (i.e. HLA matched or mismatched related or unrelated) stem cell transplants will have fulfilled eligibility for and consented to stem cell donation as per the stem cell transplant program's standard operating procedures. EXCLUSION CRITERIA: Exclusion Criteria for initial CTL and for subsequent infusions: 1. Patients receiving ATG, or Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment. 2. 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. 3. Patients who have received donor lymphocyte infusion (DLI) within 28 days. 4. Patients with active acute GVHD grades II-IV. 5. Active and uncontrolled relapse of malignancy. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | Houston Methodist Hospital | Houston | Texas |
United States | Texas Children's Hospital | Houston | Texas |
Lead Sponsor | Collaborator |
---|---|
Baylor College of Medicine | Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, The Methodist Hospital System |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Assessment of dose limiting toxicity in subjects receiving rapidly-generated donor-derived multivirus-specific CTLs | Safety and toxicity outcomes including DLTs, GvHD, clinical signs of viral infections, secondary graft failure and laboratory measurements will be summarized using descriptive statistics for each dose level (frequency table, means, standard deviations, medians and ranges). | 42 days | Yes |
Primary | Determine the effect of rCTL infusion on viral load | Primary endpoint for the phase II portion of the study is antiviral efficacy, and is whether the institution of additional antiviral therapy post rCTL is needed. | 1 year | No |
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