Autologous Cytomegalovirus (CMV) Specific CD8+ T Cells as Treatment for CMV Reactivation

Sponsor

Imperial College London (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01326273

Collaborator

(none)

Enrollment

Location

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators will assess whether the infusion of autologous CMV-specific T-cells at the time of CMV reactivation posttransplant will prevent worsening of CMV virus reactivation posttransplant to a level that warrants therapy with antiviral drugs (objectively assessed by looking at CMV virus copy number).

Condition or Disease	Intervention/Treatment	Phase
CMV Reactivation Allogeneic Stem Cell Transplantation Autologous CMV Specific CD8+ T Cells	Procedure: Lymphopheresis Procedure: CMV specific lymphocyte infusion Procedure: Peripheral blood for CMV DNA PCR Procedure: Haematology/Blood chemistry	Phase 1/Phase 2

Detailed Description

Allogeneic Hematopoietic Stem Cell transplantation (allo-SCT) remains the only curative approach for a number of patients with hematological malignancies. However, the use of allo-SCT can expose patients to prolonged periods of immunosupression during which time viral infections can be a significant cause of morbidity and mortality.

Human cytomegalovirus (CMV) infection and reactivation still represents one of the most important and lifethreatening complications in immunocompromised patients. Prophylaxis or early treatment with antiviral drugs after CMV reactivation have reduced the mortality related to this complication. However, the antiviral drugs have many side-effects and are costly. Furthermore, CMV infection refractory to antiviral treatment after alloSCT is associated with a high mortality. A number of studies have shown the efficacy of selecting Tcells against the virus from the donor and infusing them into the recipient (adoptive transfer of immunity) to prevent or treat CMV reactivation. However this approach relies on the donor having preexisitng immunity to CMV (50% of the healthy population is CMV seronegative and therefore have no preexisting immunity against CMV). We propose an alternative approach to collect CMV specific Tcells from the seropositive recipient prior to transplantation; the autologous CMV specific T cells will then be infused back into the recipient at the time of CMV reactivation post-transplant.

This approach is especially relevant where the donor is CMV seronegative or unavailable or following the use of cord blood transplant where there is no memory T cell response to CMV.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Adoptive Transfer of Autologous CMV Specific CD8+ T Cells After Allogeneic Stem Cell Transplantationas Treatment for CMV Reactivation: A Phase I/II Clinical Trial.

Study Start Date :

Apr 1, 2011

Anticipated Primary Completion Date :

Jun 1, 2014

Anticipated Study Completion Date :

Jun 1, 2014

Outcome Measures

Primary Outcome Measures

Response to adoptive transfer of autologous CMV-specific CD8+ T-cells [Up to three years]
Response to CMV-specific CD8+ T-cells administration will be measured and defined as a CMV DNA PCR< 50 copies.

Secondary Outcome Measures

The occurrence of subsequent CMV reactivations [Up to three years]
The occurrence of subsequent CMV reactivations.
Rate of complete response [Up to three years]
The rate of complete response will be analyzed and compared to patients treated with anti-viral drugs only.
Rate of early complete response [Up to three years]
The rate of early complete response will be analyzed and compared to patients treated with anti-viral drugs only.
Rate of subsequent CMV reactivation [Up to three years]
The rate of subsequent CMV reactivation will be analyzed and compared to patients treated with anti-viral drugs only.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have received an allogeneic stem cell transplant from any donor, as treatment for a haematological malignancy.
HLAA0201 positive at one allele
CMV seropositive
The patient must be willing and capable of donating lymphocytes for CMVspecific CD8+ T cell selection using apheresis techniques
The patient must be in complete remission with no evidence of circulating blasts or other malignant cells
Patient must be fit to undergo leukapheresis
Patients must have signed an informed consent form before undergoing LP prior to alloSCT

Indications for infusion of autologous CMV specific CD8+ Tcells:

Therapeutic: CMV disease following allogeneic stem cell transplantation
Preemptive: CMV reactivation (by CMV DNA PCR)
autologous CMV specific CD8+ T-cells must be infused into the patient no later than 72 following CMV reactivation.
Steroids should be withdrawn at least 1 week before the infusion of CMVspecific CD8+ T-cell
Patients must have signed an informed consent form before the infusion of autologous CMV specific CD8+ T-cells

Exclusion Criteria:

Patient CMV seronegative
No informed consent
Patient positive at the time of LP for one of the following infectious agents: HIV, HBV, HCV,Syphilis, HTLV 1 and 2
Patient with circulating leukemic blasts at the time of LP