Emergency Use of Donor Lymphocytes in Treating Patients Who Have Undergone Donor Stem Cell Transplant and Have Cytomegalovirus Infections

Cancer Clinical Trial

Official title:

Emergency Access to C.V. pp65 / IE-1 Specific Cytotoxic T Lymphocytes for Recipients of Allogeneic Stem Cell Transplants With Persistant or Therapy Refractory Infections

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00769613
• Other study ID #: CDR0000615167
• Secondary ID: PSCI-PSHCI-08-05
• Status: Active, not recruiting
• Phase: Phase 1
• First received: October 8, 2008
• Last updated: December 17, 2013
• Start date: August 2008

Study information

• Verified date: August 2010
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: White blood cells that have been treated in the laboratory may kill cells that are infected with cytomegalovirus.

PURPOSE: This phase I trial is studying how well cytotoxic T cells work in treating patients who have undergone donor stem cell transplant and have cytomegalovirus infections.

Description:

OBJECTIVES:

Primary

• To provide access to cytomegalovirus (CMV) pp65- and IE-1-specific cytotoxic T lymphocytes (CTL) in patients with persistent CMV infections after allogeneic stem cell transplantation.

Secondary

• To characterize CMV pp65- and IE-1-specific immune responses in terms of cytotoxicity and cytokine production pre-infusion and then periodically thereafter.

• To characterize the levels of CMV DNA in recipients of CMV pp65- and IE-1-specific CTL and observe whether the CTL infusion has any impact on level of virus.

• To determine the feasibility of CMV CTL culture from CMV-seronegative donors who have received a CMV vaccine.

OUTLINE: This is a multicenter study.

Patients receive allogeneic cytomegalovirus (CMV) pp65- and IE-1-specific cytotoxic T-cell lymphocytes infusion over 5 minutes on day 1. Patients may receive up to 2 more doses at least 2 weeks after previous dose.

Blood samples are collected and analyzed by quantitative CMV PCR, chromium-release assays for CMV pp65- and IE-1-specific cytotoxicity, and immunophenotype for CD3, CD4, CD8, CD56, CD19, and CD45RA/RO. Intracellular cytofluorometry is used to assess IL-2, IL-4, IL-10, and IFN-γ production by CD4 and CD8 CMV-specific effector cells.

After completion of study therapy, patients are followed periodically for up to 1 year.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Recipient of an allogeneic stem cell transplantation

• Cytomegalovirus (CMV)-seropositive and meeting 1 of the following criteria:

• Patient has a history of CMV antigenemia for = 2 weeks

• CMV DNA levels = 600 copies/mcg of DNA despite antiviral therapy targeting CMV (e.g., ganciclovir or foscarnet)

• No ongoing graft-vs-host disease

• Has donor available for peripheral blood mononuclear cell collection (for cytotoxic T lymphocytes production), meeting either of the following criteria:

• CMV-seropositive donor (= 2 years of age)

• CMV-seronegative related donor (= 18 years of age) who consents to receive the CMV vaccine

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-3 OR Lansky PS 50-100% (for patients < 16 years of age)

• Bilirubin < 2.0 mg/dL

• AST and ALT < 2.5 times normal

• Creatinine clearance = 30 mL/min

• Pulse oximetry = 94% on no more than 40% oxygen by face mask

• Not moribund

• No patients expected to survive = 1 month after the T-cell infusion due to cardiac, pulmonary, renal, hepatic, or neurologic dysfunction

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Must be on = 1 mg/kg/day of prednisone or its equivalent at the time of study CTL infusion

Study Design

Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Cancer
• Cytomegalovirus Infections

Intervention

Biological:
• cytomegalovirus IE-1-specific cytotoxic T lymphocytes

• cytomegalovirus pp65-specific cytotoxic T lymphocytes

• therapeutic allogeneic lymphocytes

Genetic:
• polymerase chain reaction

Other:
• flow cytometry

• immunological diagnostic method

• laboratory biomarker analysis

Locations

Country	Name	City	State
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety			Yes
Primary	Toxicity			Yes
Secondary	Time to development of cytomegalovirus (CMV)-specific immune reconstitution			No
Secondary	CMV DNA levels			No
Secondary	Time during post-infusion follow-up at which the dominant CMV pp65- and IE-1 epitopes for the donor is recognized by the cytotoxic T-cell lymphocytes (CTL)			No
Secondary	Feasibility of CMV pp65- and IE-1 CTL culture after CMV vaccination of seronegative donors			No