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

This study has been completed.
Sponsor:
Collaborators:
Wellcome Trust
EMAS Pharma
Commitum AB
BioAnaLab
Information provided by (Responsible Party):
Cell Medica Ltd
ClinicalTrials.gov Identifier:
NCT01077908
First received: February 26, 2010
Last updated: October 29, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Cytomegalovirus Infection
Biological: Adoptive Cellular Therapy
Drug: Best available antiviral drug therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Cell Medica Ltd:

Primary Outcome Measures:
  • CMV reactivations [ Time Frame: Six months ] [ Designated as safety issue: No ]

Estimated Enrollment: 91
Study Start Date: July 2008
Study Completion Date: October 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
Active Comparator: Best available antiviral drug therapy 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

Detailed Description:

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)

  Eligibility

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

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
  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: NCT01077908

Locations
United Kingdom
Birmingham Heartlands Hospital
Birmingham, West Midlands, United Kingdom
St James's University Hospital
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Queen Elizabeth Hospital
Birmingham, United Kingdom
Bristol Royal Hospital for Children
Bristol, United Kingdom, BS2 8BJ
Addenbrookes Hospital
Cambridge, United Kingdom, CB2 0QQ
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
Royal Liverpool Hospital
Liverpool, United Kingdom
University College Hospital
London, United Kingdom, WC1E 6BT
Kings College Hospital
London, United Kingdom
Royal Free Hospital
London, United Kingdom
Christie Hospital
Manchester, United Kingdom
Manchester Royal Infirmary
Manchester, United Kingdom
City Hospital
Nottingham, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
Sponsors and Collaborators
Cell Medica Ltd
Wellcome Trust
EMAS Pharma
Commitum AB
BioAnaLab
Investigators
Study Chair: Karl S Peggs University College London Hospitals
  More Information

No publications provided

Responsible Party: Cell Medica Ltd
ClinicalTrials.gov Identifier: NCT01077908     History of Changes
Obsolete Identifiers: NCT01115816
Other Study ID Numbers: CM-2008-01, 08/H0720/15, 74928896
Study First Received: February 26, 2010
Last Updated: October 29, 2014
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Cell Medica Ltd:
Adoptive cellular therapy
Hematopoietic Stem Cell Transplantation

Additional relevant MeSH terms:
Cytomegalovirus Infections
DNA Virus Infections
Herpesviridae Infections
Virus Diseases
Antiviral Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014