Donor-Derived Anti-viral CTLs for Treatment of Viral Infections After Allogeneic Stem Cell Transplant

Anti-viral Treatment Following Bone Marrow Transplant

Sponsors

Lead sponsor: Children's Hospital Medical Center, Cincinnati

Collaborator: Hoxworth Blood Center

Source Children's Hospital Medical Center, Cincinnati
Brief Summary

In this research study, we want to learn more about the use of donor-derived cytotoxic T-cells (CTLs) to treat viral infections that occur after allogeneic stem cell transplant. A cytotoxic T cell is a T lymphocyte (a type of white blood cell) that kills cells that are infected (particularly with viruses). Allogeneic means the stem cells come from another person. These CTLs are cells specially designed to fight the virus infections that can happen after a bone marrow transplant.

We are asking people who have undergone or will undergo an allogeneic stem cell transplant to enroll in this research study, because viral infections are a common problem after allogeneic stem cell transplant and can cause significant complications including death.

Stem cell transplant reduces a person's ability to fight infections. There is an increased risk of getting new viral infections or reactivation of viral infections that the patient has had in the past, such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus (ADV), and BK virus (BKV). There are anti-viral medicines available to treat CMV, EBV, ADV, and BK infections, though not all patients will respond to the standard treatments. Moreover, treatment of viral infections is expensive and time consuming, with families often administering prolonged treatments with intravenous anti-viral medications, or patients requiring prolonged admissions to the hospital. The medicines can also have side effects like damage to the kidneys or reduction in the blood counts, so in this study we are trying to find an easier way to treat these infections.

Detailed Description

The stem cell matched donor will be asked to give us a blood donation for the CTLs generation. In the laboratory, we will treat this blood sample to select out the cells that will help fight viruses. The cells will be grown with peptides (protein fragments that represent parts of the virus that will encourage the donor immune cells to grow). We will then grow the cells in the laboratory so that we will have a stock of virus fighting cells for the patient to use in the future. We will freeze the cells and store them in a freezer in the laboratory.

If the patient has signs of virus in their blood after the transplant we will give the cells to help fight the infection. If there are signs that the cells are helping fight the infection, we may give more cells. The patient may get the cells up to 5 times, with one month between each treatment. If the patient does not show signs of a virus, the cells will stay in the freezer.

Following CTL infusion, (s)he will be monitored with physical exams daily while inpatient and weekly while outpatient as well as blood tests weekly until 30 days after the last infusion of cells. The patient will have 3 teaspoons (15 mL) of blood drawn before each cell infusion and then once a week after each infusion for 4 weeks and then once a month if possible for 1 year after the last infusion, all to monitor for the viral response.

Overall Status Recruiting
Start Date February 5, 2014
Completion Date March 2024
Primary Completion Date March 2023
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Toxicity Patients will be monitored weekly for new onset grades 2-4 GVHD within 30 days of CTL infusion.
Secondary Outcome
Measure Time Frame
Efficacy Patients will receive physical examinations daily while inpatient. Following discharge, physical examination will be performed at least weekly until 30 days after last CTL infusion.
Enrollment 450
Condition
Intervention

Intervention type: Biological

Intervention name: Viral specific CTL Infusion

Description: CTL's will be infused into stem cell transplant recipients who have evidence of viral infection or reactivation defined as any of the following: Blood adenovirus PCR ≥ 1,000 Blood CMV PCR ≥ 500 Blood EBV PCR ≥ 9,000 Plasma BKV PCR >1,000 Evidence of invasive adenovirus infection or disease, defined as the presence of adenoviral positivity in one or more sites. Evidence of invasive CMV infection, eg pneumonitis, retinitis, colitis Evidence of EBV-associated lymphoproliferation (EBV-LPD) defined as an elevated EBV DNA level in the blood associated with clinical symptoms (adenopathy or fever or masses on imaging) but without biopsy confirmation. Evidence of symptomatic BK virus infection, which may include symptomatic hemorrhagic cystitis.

Arm group label: Viral Specific CTL Infusion

Eligibility

Criteria:

Inclusion Criteria:

- Recipient must be at least 28 days after stem cell infusion

- Clinical status must allow tapering of steroids to 0.5mg/kg prednisone or other steroid equivalent

- Recipient must have achieved engraftment with ANC ≥ 500

Exclusion Criteria:

- Active acute GVHD grades II-IV

- Uncontrolled bacterial or fungal infection

- Uncontrolled relapse of malignancy

- Infusion of ATG or alemtuzumab within 2 weeks of CTL infusion

Gender: All

Minimum age: N/A

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Michael Grimley, MD Principal Investigator Children's Hospital Medical Center, Cincinnati
Overall Contact

Last name: Jamie Wilhelm, BS

Phone: (513) 803-1102

Email: [email protected]

Location
facility status contact investigator
Cincinnati Children's Hospital Medical Center Recruiting Jamie Wilhelm 513-803-1102 Michael Grimley, MD Principal Investigator
Location Countries

United States

Verification Date

January 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Viral Specific CTL Infusion

Arm group type: Experimental

Description: Viral reactivation or infection. CTL Reinfusion required.

Acronym CTLs
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov