Adoptive Cord Blood Immunotherapy for EBV, CMV, BKV and Adenovirus Reactivation/Infection or Prophylaxis

STATUS

Recruiting
End date

Nov 15, 2025
participants needed

36
sponsor

Catherine Bollard

Updated on 5 March 2022

See if I qualify

absolute neutrophil count

nephropathy

cmv infection

Summary

This Phase I-II dose-finding trial to determine the optimal dose of intravenous (IV) injection dose of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, BKV and Adenovirus. A maximum of 36 patients will be treated in up to 18 cohorts each of size 2, with the first cohort treated at the lowest dose level 1, all successive doses chosen by the EffTox method, and no untried dose level skipped when escalating.

The scientific goal of the trial is to determine an optimal IV-CTL cell dose level among the three doses 1.0x107cells/m2, 2 x107cells/m2 and 5x107cells/m2., hereafter dose levels 1, 2, 3. Dose-finding will be done using the sequentially adaptive EffTox trade-off-based design of Thall et al.

Description

CMV/AdV /EBV/BKV specific T cells will be thawed and given or thawed and diluted into a total volume of 10 mL of Plasmalyte A by slow intravenous injection over 1-2 minutes. This is a traditional Phase I dose escalation study of a single infusion of CMV/AdV/EBV/BKV-specific CTLs to patients at risk for CMV and EBV reactivation and Adenoviral and BK virus infection after umbilical cord blood transplantation. Three dose levels will be explored. The lowest dose level will be 1x107cells/m2 and the highest will be 5x107/m2. There will be 2-6 patients at each dose level (depending on toxicity) following the scheme below. The decision on whether it is safe to escalate to next dose level or not will be made after at least two patients in each dose level have finished their 45-days toxicity follow up. If the first two patients have not finished their 45 days follow-up, up to 2 additional incoming patients can be enrolled at the current dose level. In addition, we will give the option of administering 2 additional doses (at the same dose level), 28 days after the first infusion of the same dose, in subjects who have a partial response after one dose or who have received other therapy that may affect the persistence or function of the infused CTL in vivo. If there are no toxicities and immunological efficacy is not seen at any dose, then the doses will be further escalated after additional local and federal approval.

Dose Levels and Dosing Schedule

Dose Level CTL Dose Given from Day +30 post SCT

1x107/m2
2.0x107/m2
5x107/m2

Escalation of Multi-virus-specific CTL infusions

CMV/AdV/EBV/BKV CTL will be given from day +30 either as prophylaxis or treatment for CMV, EBV, BK and/or adenovirus infection. If the patient has viral reactivation or evidence of CMV/EBV/AdV/BKV disease (e.g. pneumonitis, gastroenteritis and/or retinitis or Post Transplant Lymphoproliferative Disorder (PTLD) or hemorrhagic cystitis the CTL can be given with concurrent antiviral pharmacotherapy.

A dose escalation scheme utilizing cohorts of two patients will be used

Each cohort of 2 patients will be treated and observed for 45 days for toxicity, dose escalation, and GvHD. The algorithm described in Section 9 will be used to determine the dose for each cohort. If 1x107CTL/m2 results in unacceptable toxicity or efficacy, the study will be closed to accrual.

The Optimal Dose of Infused CMV/AdV/EBV/BKV-Specific CTL

After all patients in the trial have been evaluated, the optimal dose of infused CMV/AdV/EBV-specific CTL will be determined by the algorithm using the sequentially adaptive EffTox trade-off-based design of Thall et al.

Details

Condition	Viral Infection
Treatment	CMV/AdV /EBV/BKV specific T cells
Clinical Study Identifier	NCT03594981
Sponsor	Catherine Bollard
Last Modified on	5 March 2022

How understandable was the trial content above?

Hard to understand

Easy to understand

Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Inclusion Criteria at the Time of Procurement
	Pediatric and adult patients (there are no lower and upper age limits for patients) with malignant or nonmalignant diseases who are candidates for transplant
	Patients must have a CB unit (or units) matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. The unit selected for CTL expansion must be either
	be cryopreserved in two fractions, with a minimum of 2.5x107 total nucleated cells (TNC) per kg pre-thaw in the fraction which will be used for the primary transplant. The remaining fraction will be used to generate the CTLs to give at day 30 or beyond as described below. OR
	be cryopreserved with a cell dose that totals > 3x10e7 TNC per kg pre thaw. On thaw, 20% of the total volume will be used for CTL manufacture to give at day 30 or beyond and the remaining 80% will be used for the primary transplant
	For recipients of double CBT, if possible both CB units should be cryopreserved in two fractions and T-cells will be made from both units if possible
	Inclusion Criteria at the Time of CTL Infusion
	Recipients of at least one unmanipulated cord blood unit as described above (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with CMV/Adenoviral/BKV and/or EBV infection or reactivation
	Lansky/Karnofsky scores 60
	Absolute neutrophil count (ANC) greater than 500/u
	No evidence of GVHD > Grade II at time of enrollment
	Life expectancy > 30 days
	Absence of severe renal disease (Creatinine < 3x normal for age)
	Absence of severe hepatic disease. Direct bilirubin must be < 3 mg/dl and AST < 5x upper limit of normal
	Patient must be at least 30 days post transplant to be eligible to receive CTL
	Written informed consent and/or signed assent line from patient, parent or guardian
Exclusion Criteria
	Exclusion Criteria at the Time of Procurement
	Pregnant or lactating
	Patients with active central nervous system disease
	Patients with Karnofsky performance status <70%
	Patients with grade 3 or 4 or primary myelofibrosis
	Patients with suitable related donors Exclusion Criteria at the Time of CTL Infusion
	Pregnant or lactating
	Patient on Fi02 of >60%
	Unable to wean steroids to 0.5 mg/kg/day prednisone or equivalent
	Patients with Grade 3 hyperbilirubinemia
	Patients with other uncontrolled infections (except CMV and/or adenovirus and/or EBVemia and/or BK viruria/viremia). For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection
	Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease
	Patients who have received investigational (IND) product within 28 days of screening for CTL infusion under this study

How to participate?

Step 1 Connect with a study center

Select a site
Send a message

You have contacted , on

Your message has been sent to the study team at ,

A copy of the message has been sent to your email

What happens next?

You can expect the study team to contact you via email or phone in the next few days.
Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Primary Contact

0/250

By sending a message, I agree that my data will be sent to a representative for the selected site and processed in accordance with this website's Privacy Policy (see link in footer).

Step 2 Get screened

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

Step 3 Enroll in the clinical study

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Step 4 Get your study results

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Browse trials for

absolute neutrophil count

nephropathy

cmv infection

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Edit Delete

Added by •

•

Private

Edit Delete

Reply by • • Private

Edit Delete

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

Enter the passcode

The passcode will expire in None.

Adoptive Cord Blood Immunotherapy for EBV, CMV, BKV and Adenovirus Reactivation/Infection or Prophylaxis