Cytomegalovirus - Immunoprophylactic Adoptive Cellular Therapy Study (CMV-IMPACT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Cell Medica Ltd
Sponsor:
Collaborators:
Wellcome Trust
EMAS Medical Ltd
Commitum AB
BioAnaLab
Information provided by (Responsible Party):
Cell Medica Ltd
ClinicalTrials.gov Identifier:
NCT01077908
First received: February 26, 2010
Last updated: May 14, 2014
Last verified: May 2014

February 26, 2010
May 14, 2014
July 2008
August 2014   (final data collection date for primary outcome measure)
CMV reactivations [ Time Frame: Six months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01077908 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Cytomegalovirus - Immunoprophylactic Adoptive Cellular Therapy Study
A Phase III Randomised Study to Investigate the Use of Adoptive Cellular Therapy (ACT) in Combination With Conventional Antiviral Drug Therapy for the Treatment of CMV Reactivation Episodes in Patients Following Allogeneic Haematopoietic Stem Cell Transplant

The purpose of this study is to evaluate the potential clinical benefit of prophylactic cytomegalovirus (CMV)-specific adoptive cellular therapy following T cell depleted allogeneic hematopoietic stem cell transplantation (HSCT) for reducing recurrent CMV reactivation.

As with other herpes viruses, CMV infection is thought to result most frequently from reactivation of latent virus. Transmission of the virus can also occur from donor marrow infusion or from allogeneic red cell, leukocyte or platelet transfusions. In an allogeneic haematopoietic stem cell (bone marrow) transplant patient who is CMV seropositive or receiving a transplant from a donor who is CMV seropositive, CMV frequently reactivates and disease resulting from the progression of infection is a major cause of infectious morbidity and mortality. CMV infection is a consequence both of the immunosuppression these patients receive and may also reflect delayed immune reconstitution in these patients following transplant.

Existing evidence suggests that adoptive cellular therapy can be an effective approach for treating viral reactivation following allo HSCT, with a minimal risk of inducing GVHD. The major advantage to the patient is likely to be avoidance of extended periods of therapy with antiviral medications that have significant associated morbidities, and sometimes require inpatient care. A proof of efficacy in the sibling donor setting would strengthen the case for extending the therapy to the unrelated donor setting, where both potential risks and benefits are greater. From a pharmacoeconomic viewpoint, the avoidance of the costs associated with these treatment episodes could offset the costs of adoptive cellular therapy. A number of issues remain unresolved. These include the relative contributions of transferred CD4+ and CD8+ T cell populations (which may have direct relevance to the best approach for selection), the issue of whether adoptive cellular therapy improves outcomes in a randomised setting, and equally importantly, the issue of whether such immunotherapies can be delivered outside of the setting of a few academic institutions on a multicentre basis.

These considerations emphasise the importance of undertaking a randomised phase III study of prophylactic adoptive cellular therapy for CMV following T cell depleted allogeneic HSCT from a sibling donor (CMV~IMPACT). There are multiple methods for T cell depletion available, and differences between them will likely have an effect on immune reconstitution. In order to avoid this confounding influence the study will be restricted to patients receiving alemtuzumab-containing conditioning protocols.

In summary, this study is a multicentre, prospective, controlled, open-label 3 arm randomized study comparing 'best-available' standard anti-viral monitoring and therapy alone, with 'best available'anti-viral monitoring and therapy plus prophylactic adoptive cellular therapy (ACT) with cells selected by either the Gamma Catch or Multimer Selection techniques. Patients will be randomised to:

A. Standard best available antiviral drug therapy alone B. Immunoprophylactic (Day 27) ACT prepared using Gamma Catch Selection in combination with standard best available antiviral drug therapy C. Immunoprophylactic (Day 27) ACT prepared using Multimer Selection in combination with standard best available antiviral drug therapy

The study will test the hypothesis that CMV-specific ACT based upon a prescribed T-cell dose/kg recipient body weight, can augment the impaired CMV immune function post-transplant and reduce the number of recurrent reactivations in patients following a primary reactivation event (and thereby reduce the requirement for antiviral drug therapy) without causing an increase in GVHD.

Individual groups will be compared for duration of antiviral therapy and number of reactivation episodes, plus GVHD incidence. Similar analyses will be performed for adoptive cellular therapy versus no therapy (i.e. (B+C) versus A)

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Cytomegalovirus Infection
  • Biological: Adoptive Cellular Therapy
    CMV-specific T-cells, single infusion at 27 days post-HSCT
  • Drug: Best available antiviral drug therapy
    1. Intravenous ganciclovir 5mg/kg twice daily
    2. Oral valganciclovir 900mg twice daily
    3. Intravenous foscarnet 90 mg/kg twice daily
  • Experimental: ACT plus standard therapy
    Adoptive Cellular Therapy (ACT) prepared using Multimer or Gamma Catch Selection in combination with standard best available antiviral drug therapy
    Interventions:
    • Biological: Adoptive Cellular Therapy
    • Drug: Best available antiviral drug therapy
  • Active Comparator: Best available antiviral drug therapy
    Intervention: Drug: Best available antiviral drug therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
91
September 2014
August 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Suitable participants will be selected from patients already scheduled to undergo a T cell depleted sibling donor HSCT. The criteria will include:
  • Age 18 years or older
  • Negative markers of Infectious Disease screen
  • Recipient of allogeneic HSCT (that incorporates T cell depletion with alemtuzumab) who is CMV seropositive with a CMV seropositive sibling donor
  • Informed consent from both donor and patient and to be assessed prior to CMV-specific T cell infusion (confirmed prior to product release):
  • Donor engraftment (neutrophils > 0.5x109/l)

Exclusion Criteria:

  • Pregnant or lactating women
  • Co-existing medical problems that would place the patient at significant risk of death due to GVHD or its sequelae
  • HIV infection and to be assessed prior to CMV-specific T cell infusion (confirmed prior to product release):
  • Active acute GVHD > Grade I
  • Concurrent use of systemic corticosteroids
  • Organ dysfunction as measured by

    1. creatinine > 200 uM/l
    2. bilirubin > 50 uM/l
    3. ALT > 3x upper limit of normal
Both
18 Years and older
No
Contact: Karen L Hodgkin +44 207 554 4070 karen.hodgkin@cellmedica.co.uk
United Kingdom
 
NCT01077908
CM-2008-01, 08/H0720/15, 74928896
Yes
Cell Medica Ltd
Cell Medica Ltd
  • Wellcome Trust
  • EMAS Medical Ltd
  • Commitum AB
  • BioAnaLab
Study Chair: Karl S Peggs University College London Hospitals
Cell Medica Ltd
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP