Using virus-specific T-cells to treat CMV infections in young patients

A Pilot Study in the Treatment of Refractory Cytomegalovirus (CMV) Infections With Related Donor CMV Specific Cytotoxic T-cells (CTLs) in Children, Adolescents and Young Adult Recipients

This study is testing a new treatment using special immune cells to help children and young adults with stubborn CMV infections after organ transplants when regular medicines haven’t worked.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 1 Month to 79 Years
• Sex: All
• Sponsor: New York Medical College (other)
• Drugs / interventions: Alemtuzumab, prednisone
• Locations: 9 sites (Los Angeles, California and 8 other locations)
• Trial ID: NCT03266640 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to administer cytotoxic T-lymphocytes (CTLs) specifically targeting cytomegalovirus (CMV) to children, adolescents, and young adults suffering from refractory CMV infections following allogeneic hematopoietic stem cell transplantation or solid organ transplantation. The CTLs are manufactured using the Miltenyi CliniMACS Prodigy Cytokine Capture System and are intended for patients who have not responded to standard antiviral therapies. The study will evaluate the safety and efficacy of this innovative treatment approach in a vulnerable patient population with primary immune deficiencies.

Who should consider this trial

Good fit: Ideal candidates for this study are children, adolescents, and young adults with refractory CMV infections post-transplant who have not responded to antiviral therapies.

Not a fit: Patients who do not have refractory CMV infections or those who are not post-transplant may not receive any benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with refractory CMV infections, potentially improving their health outcomes and quality of life.

How similar studies have performed: Other studies have shown promise in using virus-specific T-cells for treating viral infections, suggesting that this approach may be effective.

Eligibility criteria

1\. Patients with refractory CMV infection post allogeneic HSCT, with primary immunodeficiencies or post solid organ transplant with either

* Increasing or persistent quantitative qRT-PCR DNA copies despite two weeks of appropriate anti-viral therapy AND/OR
* Medical intolerance to anti-viral therapies including:
* ANC \< 500/mm2 secondary to ganciclovir

  * 2 renal toxicity with foscarnet And/or
* known resistance to ganciclovir and/or foscarnet

Consent: Written informed consent given (by patient or legal representative) prior to any study-related procedures.

Performance Status \> 30% (Lansky \< 16 yrs and Karnofsky \> 16 yrs) Age: 0.1 to 79.99 years Females of childbearing potential with a negative urine pregnancy test

Donor Eligibility Related donor available with a T-cell response to the CMV MACS® GMP PepTivator antigen(s).

a. Third Party Allogeneic Donor: If original donor is not available or does not have a T-cell response: third party related allogeneic donor (family donor \> 1 HLA A, B, DR match to recipient) with IgG positive to CMV and/or a T-cell response to the CMV MACS® GMP PepTivator .

AND Allogeneic donor disease screening is complete similar to hematopoietic stem cell donors (Appendix 1).

AND Obtained informed consents by donor or donor legally authorized representative prior to donor collection.

3 Patient exclusion criteria:

A patient meeting any of the following criteria is not eligible for the present study:

Patient with acute GVHD \> grade 2 or extensive chronic GVHD at the time of CMV CTL infusion Patient receiving steroids (\>0.5 mg/kg prednisone equivalent) at the time of CMV CTL infusion Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CMV CTL infusion Thymoglobulin (ATG), Alemtuzumab or T cell immunosuppressive monoclonal antibodies within 30 days Patient with poor performance status determined by Karnofsky (patients \>16 years) or Lansky (patients ≤16 years) score ≤30% CMV retinitis Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory CMV infection.

Any medical condition which could compromise participation in the study according to the investigator's assessment Known HIV infection Female patient of childbearing age who is pregnant or breast-feeding or not willing to use an effective method of birth control during study treatment.

Known hypersensitivity to iron dextran Patients unwilling or unable to comply with the protocol or unable to give informed consent.

Known human anti-mouse antibodies CMV retinitis, meningitis, encephalitis, and/or cerebritis

Where this trial is running

Los Angeles, California and 8 other locations

• Children's Hospital Los Angeles — Los Angeles, California, United States (RECRUITING)
• University of California San Francisco — San Francisco, California, United States (RECRUITING)
• Indiana University — Indianapolis, Indiana, United States (RECRUITING)
• Johns Hopkins — Baltimore, Maryland, United States (RECRUITING)
• Washington University — St Louis, Missouri, United States (RECRUITING)
• New York Medical College — Valhalla, New York, United States (RECRUITING)
• Nationwide Children's Hosptial — Columbus, Ohio, United States (RECRUITING)
• Children's Hospital of Pennsylvania — Philadelphia, Pennsylvania, United States (RECRUITING)
• Medical College of Wisconsin/Children's Hospital of Wisconsin — Milwaukee, Wisconsin, United States (RECRUITING)

Study contacts

• Principal investigator: Mitchell S Cairo, MD — New York Medical College
• Study coordinator: Mitchell S Cairo, MD

Conditions: Cytomegalovirus Infections, Primary Immune Deficiency Disorder, Cytomegalovirus, CMV, cytotoxic t-lymphocytes