Family-donor viral CTLs plus standard care vs standard care alone for refractory ADV or CMV infection after stem cell transplant

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a phase 3 randomized trial enrolling patients who have ongoing or resistant CMV or adenovirus infections after allogeneic hematopoietic stem cell transplantation. Participants are assigned to receive either family donor–derived viral-specific cytotoxic T lymphocytes (CTLs) plus standard antiviral care or standard antiviral care alone. CTLs are manufactured using direct selection with the CliniMACS Prodigy and Cytokine Capture System. The primary outcome is Day 100 viral progression-free survival, reflecting the ability to control viremia without viral progression. The study targets children, adolescents, and young adults and is conducted at two academic centers in the United States.

Why it matters

Who can join: the full rules

Patient Eligibility Cohort 1 (ADV) -Patients with ADV viremia (Cohort 1) post AlloHSCT with one or more of the following: Increasing or persistent ADV RT-PCR DNA (\> 1000 ADV PCR copies) after 7 days of appropriate anti-viral therapy AND/OR Medical intolerance to anti-viral therapies including one or more of the following: \> grade 2 renal insufficiency secondary to cidofovir and/or other \> grade 2 toxicities secondary to cidofovir AND/OR Known resistance to cidofovir

Patient Eligibility (Cohort 2) (CMV)

-Patients with CMV viremia with one or more of the following: Increasing or persistent CMV RT-PCR DNA (\>1000 copies) after 7 days of appropriate anti-viral therapy AND/OR Medical intolerance to anti-CMV antibiotic therapies: ANC \< 500/mm3 secondary to ganciclovir AND/OR \> grade 2 renal toxicity secondary to either foscarnet or cidofovir 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 years (BOTH COHORTS)
* Age: 0.01 to 30.00 years (BOTH COHORTS)
* Females of childbearing potential with a negative urine pregnancy test at study entry only (BOTH COHORTS)
* Family related donor (\> 3 HLA match) that screens positive for ADV5 MACS Peptivator (Cohort 1) or PP65CMV MACS Peptivator (Cohort 2)

Donor Eligibility

* Related donor available with a T-cell response to the ADV MACS PepTivators (Cohort 1) or CMV MACS PepTivator (Cohort 2). As defined in Appendix II, B, 8.2, the donor is considered suitable if the percentage of IFN+ T-cells is \>0.01% after stimulation with ADV PepTivators (Cohort 1) or CMV PepTivators (Cohort 2).
* Third-party related allogeneic donor: If original donor is not available or does not have a T-cell response to ADV MCAS PepTivator (Cohort 1) or CMV PepTivator (Cohort 2), third party allogeneic donor (family donor \> 3 HLA A, B, DR match to recipient) with a T-cell response at least to the ADV MCAS PepTivator (Cohort 1) or CMV PepTivator (Cohort 2) 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

Patient Exclusion Criteria (Both Cohorts)

* Patient with acute GVHD \> grade 2 or moderate or extensive chronic GVHD at the time of CTL infusion.
* Patient receiving steroids (\>0.5 mg/kg prednisone equivalent) at the time of CTL infusion.
* Patient treated with donor lymphocyte infusion (DLI) within 4 weeks prior to CTL infusion.
* Patient with poor performance status determined by Karnofksy (patients \> 16 yrs) or Lansky (patients \< 16 years) score \< 30%.
* Concomitant enrollment in another experimental clinical trial investigating the treatment of refractory ADV or CMV infections.
* Any known medical condition which cold compromise participation in the study according to investigators assessment.
* Known AIDS or uncontrolled HIV infection
* Known hypersensitivity to iron dextran
* Encephalitis and/or retinitis

Where it's running

• New York Medical College
  Valhalla, New York, United States Recruiting
• Medical College of Wisconsin
  Milwaukee, Wisconsin, United States Not yet recruiting

Study contacts

• Principal investigator: Mitchell Cairo, MD — New York Medical College
• Study coordinator: Mitchell Cairo, MD
• Email: mitchell_cairo@nymc.edu
• Phone: 914-594-2150

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.