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

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Allogeneic Stem Cell Transplantation; CMV Reactivation; Autologous CMV Specific CD8+ T Cells
• Intervention / Treatment: Procedure: Lymphopheresis; Procedure: CMV specific lymphocyte infusion; Procedure: Peripheral blood for CMV DNA PCR; Procedure: Haematology/Blood chemistry

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 Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have received an allogeneic stem cell transplant from any donor, as treatment for a haematological malignancy.
2. HLAA0201 positive at one allele
3. CMV seropositive
4. The patient must be willing and capable of donating lymphocytes for CMVspecific CD8+ T cell selection using apheresis techniques
5. The patient must be in complete remission with no evidence of circulating blasts or other malignant cells
6. Patient must be fit to undergo leukapheresis
7. 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:

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

Exclusion criteria for infusion of autologous CMV specific CD8+ T cells:

Severe GvHD (grade IIII-V) requiring full dose immunosuppressive treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Imperial College London

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Anticipated): June 1, 2014
• Study Completion (Anticipated): June 1, 2014

Study Registration Dates

• First Submitted: March 22, 2011
• First Submitted That Met QC Criteria: March 29, 2011
• First Posted (Estimate): March 30, 2011

Study Record Updates

• Last Update Posted (Estimate): June 8, 2015
• Last Update Submitted That Met QC Criteria: June 3, 2015
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: stem cell transplantation; cytomegalovirus; CMV; autologous; hematological malignancies; leukemia; CMV reactivation; adoptive therapy
• Other Study ID Numbers: JROHH0202