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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01326273
First received: March 22, 2011
Last updated: March 22, 2012
Last verified: March 2012
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Response to adoptive transfer of autologous CMV-specific CD8+ T-cells [ Time Frame: Up to three years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to three years ] [ Designated as safety issue: Yes ]
    The occurrence of subsequent CMV reactivations.

  • Rate of complete response [ Time Frame: Up to three years ] [ Designated as safety issue: Yes ]
    The rate of complete response will be analyzed and compared to patients treated with anti-viral drugs only.

  • Rate of early complete response [ Time Frame: Up to three years ] [ Designated as safety issue: Yes ]
    The rate of early complete response will be analyzed and compared to patients treated with anti-viral drugs only.

  • Rate of subsequent CMV reactivation [ Time Frame: Up to three years ] [ Designated as safety issue: Yes ]
    The rate of subsequent CMV reactivation will be analyzed and compared to patients treated with anti-viral drugs only.


Enrollment: 0
Study Start Date: April 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Lymphopheresis
    Lymphopheresis
    Procedure: CMV specific lymphocyte infusion
    CMV specific lymphocyte infusion
    Procedure: Peripheral blood for CMV DNA PCR
    Peripheral blood for CMV DNA PCR
    Procedure: Haematology/Blood chemistry
    Haematology/Blood chemistry analysis, Collection of blood for ancillary laboratory tests.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01326273

Locations
United Kingdom
Hammersmith Hospital
London, United Kingdom, W12 0HS
Sponsors and Collaborators
Imperial College London
Investigators
Principal Investigator: Katy Rezvani, MD Imperial College Healthcare NHS Trust
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01326273     History of Changes
Other Study ID Numbers: JROHH0202
Study First Received: March 22, 2011
Last Updated: March 22, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Imperial College London:
CMV
cytomegalovirus
autologous
leukemia
hematological malignancies
stem cell transplantation
CMV reactivation
adoptive therapy

ClinicalTrials.gov processed this record on August 28, 2014