Adenovirus, AdV Infection, AdV Reactivation, CMV, Cytomegalovirus Infections
Conditions
Keywords
CMV infection, ADV Infection, cytomegalovirus, adenovirus
Brief summary
Patients with refractory ADV or CMV infection post allogeneic stem cell transplant will be randomized to either Family donor-derived viral specific cytotoxic T lymphocytes (CTLs) plus standard of care (SOC) vs SOC alone.
Detailed description
We hypothesize that Family donor-derived viral specific cytotoxic T lymphocytes (CTLs) manufactured by direct selection utilizing the CliniMACS Prodigy® and Cytokine Capture System® plus standard of care (SOC) vs SOC alone in children, adolescents and young adults (CAYA) following allogeneic hematopoietic stem cell transplantation (HSCT) with medically refractory viral infection/viremia and/or intolerant or resistant to anti-viral antibiotic therapy will be associated with a significantly improved probability of Day +100 (time of onset on study) viral progression free survival (VPFS).
Interventions
DRUGStandard of Care Antiviral medications
Standard of Care medications will be selected by the treating physician for either ADV (Cohort 1) or CMV (cohort 2)
BIOLOGICALViral CTLs
ADV or CMV family matched CTLs will be administered with SOC medications one every 2 weeks as needed up to 5 infusions
Sponsors
New York Medical College
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is a prospective, open-label, randomized trial allocating patients to CTLs+SOC and SOC only at a 2:1 ratio. Patients will be enrolled to two cohorts, Cohort 1, ADV and Cohort 2, CMV. For patients with progressive viremia/disease (PD) in the SOC arm, crossover will be allowed to receive CTLs from an eligible family related donor that has screened positive to the specific viral PepTivator.
Eligibility
Sex/Gender
ALL
Age
1 Days to 30 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Viral PCR to determine resolution of disease | Day 100 | Patients will be monitored weekly by peripheral blood qtPCR values to monitor viral levels for resolution confirmation. |
Countries
United States
Contacts
CONTACTMitchell Cairo, MD
CONTACTLauren Harrison, RN
PRINCIPAL_INVESTIGATORMitchell Cairo, MD
New York Medical College
Outcome results
None listed