Phase 3 Randomized Trial for Refractory ADV or CMV Infection With Family Matched CTLs and Standard of Care (SOC) vs SOC Alone
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Standard of Care Antiviral medications, Viral CTLs.
- Who it may be relevant to
- Registry conditions: CMV, AdV Infection, AdV Reactivation, Adenovirus. Basic parameters: 1 Day — 30 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
An Open-Label Prospective Randomized Trial of Family Donor-Derived ADV or CMV CTLs Plus Standard of Care (SOC) vs SOC Alone in Children, Adolescents and Young Adults Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) With Refractory ADV or CMV Infection/Viremia
Overview
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
- Drug Standard of Care Antiviral medications
Standard of Care medications will be selected by the treating physician for either ADV (Cohort 1) or CMV (cohort 2) - Biological Viral CTLs
ADV or CMV family matched CTLs will be administered with SOC medications one every 2 weeks as needed up to 5 infusions
Primary outcome measures
- Viral PCR to determine resolution of disease [Time frame: Day 100]
Eligibility criteria
Patient Eligibility Cohort 1 (ADV) -Patients with ADV infections (Cohort 1) (pneumonitis, hepatitis, cystitis, and/or colitis) 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 infections (pneumonitis, hepatitis, colitis) 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)
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Crossover
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Center list to be confirmed — check the primary protocol.
Identifiers
NCT: NCT07225972 · NYMC 622