Allogeneic Virus-Specific Cytotoxic T-Lymphocytes(CTL), Persistent/Recurrent Viral Infection Post-HSCT (EAP CHALLAH)

NCT01945619 | Unknown

• 2 other identifiers: H-31634, EAP CHALLAHEAP CHALLAH
• Study Type: expanded_access
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Subjects have a type of blood cell cancer, other blood disease or a genetic disease for which they received a stem cell transplant. After transplant while the immune system grows back the subjects have an infection with one or more of three viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV) or adenovirus - that has persisted or come back despite standard therapy. Adenovirus is a virus that causes symptoms of a common cold normally but can cause serious life-threatening infections in patients who have weak immune systems. It usually affects the lungs and can cause a very serious pneumonia, but it can also affect the gut, the liver, the pancreas and the eyes. CMV is a virus that can also cause serious infections in patients with suppressed immune systems. It usually affects the lungs and can cause a very serious pneumonia, but it can also affect the intestinal tract, 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. If the subject and/or the subject's donor are positive for CMV, s/he is at risk of developing CMV disease while his/her immune system is weak post transplant. EBV is the virus that causes glandular fever or kissing disease. It is also normally controlled by a healthy immune system, but when the immune system is weak, it can cause fevers, enlarged lymph nodes and sometimes develop into a type of cancer called lymphoma. This treatment with specially trained T cells (called CTLs) has had activity against these viruses when the cells are made from the transplant donor. However, as it takes 2-3 months to make the cells, that approach is not practical when the subject already has an infection. We want to find out if we can use CTLs which have already been made from another donor that match the subject and his/her donor as closely as possible and if the CTLs will last in the body and have activity against these viruses. In a recent study these cells were given to 50 patients with viral infections post transplant and over 70% had a complete or partial response. The purpose of this study is to make CTL lines leftover from that previous study available to patients with viral infections that have not responded to standard treatments. These virus-specific CTLs are an investigational product not approved by the FDA.

Conditions

EBV Infection; CMV Infection; Adenoviral Infection

Keywords

CMV; Adenovirus; EBV; Stem cell transplant; cytotoxic T-lymphocytes

Interventions

Trivirus-Specific CTLs BIOLOGICAL

Patients will receive up to 2 x 10\^7 CHM-CTL/m2 as a single infusion and may receive up to 4 additional infusions at intervals of at least 2 weeks.

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or single or double umbilical cord blood.
• CMV, adenovirus or EBV infection persistent despite standard therapy
• For CMV infection
• Patients with CMV disease: defined as the demonstration of CMV by biopsy specimen from visceral sites (by culture or histology) or the detection of CMV by culture or direct fluorescent antibody stain in bronchoalveolar lavage fluid in the presence of new or changing pulmonary infiltrates OR
• Failure of antiviral therapy: defined as the continued presence of pp65 antigenemia (\>1+ cell/100,000 cells) or DNAemia (as defined by reference lab performing PCR assay but usually \>400 copies/ml) after at least 7 days of antiviral therapy OR
• Relapse after antiviral therapy defined as recurrence of either pp65 antigenemia or DNAemia after at least 2 weeks of antiviral therapy
• For CMV infection, standard therapy is defined as 7 days therapy with Ganciclovir, Foscarnet or Cidofovir for patients with disease or recurrence after 14 days therapy
• For EBV infection
• EBV infection is defined as:
• Biopsy proven lymphoma with EBV genomes detected in tumor cells by immunocytochemistry or in situ PCR OR
• Or clinical or imaging findings consistent with EBV lymphoma and elevated EBV viral load in peripheral blood.
• For EBV infection, standard therapy is defined as rituximab given at 375mg/m2 in patients for 1-4 doses with a CD20+ve tumor
• Failure is defined as
• There was an increase or less than 50% response at sites of disease for EBV lymphoma OR
• There was a rise or a fall of less than 50% in EBV viral load in peripheral blood or any site of disease

You may not qualify if:

• Received ATG, or Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment.
• 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.
• Received donor lymphocyte infusion (DLI) within 28 days.
• Active acute GVHD grades II-IV.
• Active and uncontrolled relapse of malignancy
• Pregnant or lactating in female patients, if applicable (childbearing potential who have received a reduced intensity conditioning regimen).

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator
• Children's Hospital Los Angeles: collaborator
• Duke University: collaborator
• Hackensack Meridian Health: collaborator
• New York Medical College: collaborator
• University of Texas Southwestern Medical Center: collaborator
• Children's National Research Institute: collaborator
• Johns Hopkins All Children's Hospital: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Epstein-Barr Virus Infections; Cytomegalovirus Infections; Adenoviridae Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Study Officials

• Helen E Heslop, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: expanded access
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 16, 2013
• First Posted: September 18, 2013
• Last Updated: January 21, 2016

Record last verified: 2016-01

Locations

US (2)