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

NCT03594981 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CHEERS
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Viral Infection

Outcome Measures

Primary Outcomes (1)

• Number of participants with investigational product-related adverse events as assessed by CTCAE v4.03

  The study will determine the optimal dose of intravenous injection of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, Adenovirus and BK virus( BKV) given to patients with or at risk for CMV, EBV, BK virus and adenovirus infection after cord blood transplant. The safety will be assessed by investigational product-related adverse events as per CTCAE v4.03.

  45 days for toxicity

Secondary Outcomes (1)

• Impact of CMV/AdV /EBV/BKV specific T cells will be measured by existence of cells in the system.

  12 months

Study Arms (1)

CMV/AdV /EBV/BKV specific T cells

EXPERIMENTAL

CMV/AdV /EBV/BKV specific T cells will be thawed and transferred to a syringe given by slow intravenous injection over 1-2 minutes. Three dose levels will be explored. The lowest dose level will be 1x107cells/m2 and the highest will be 5x107/m2.

Biological: CMV/AdV /EBV/BKV specific T cells

Interventions

CMV/AdV /EBV/BKV specific T cells BIOLOGICAL

Each cohort of 2 patients will be treated and observed for 45 days for toxicity, dose escalation, and GvHD. The algorithm of sequentially adaptive EffTox trade-off-based design of Thall et al 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.

CMV/AdV /EBV/BKV specific T cells

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Catherine Bollard: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (2)

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

RECRUITING

M.D. Anderson Cancer Center (MDACC)

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Virus Diseases

Condition Hierarchy (Ancestors)

Infections

Central Study Contacts

Allistair Abraham, MD

CONTACT

202-476-5772; AAbraham@childrensnational.org

Fahmida Hoq, MBBS, MS

CONTACT

202-476-334; fhoq@childrensnational.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Center for Cancer and Immunology/ Center for Emerging Technologies in Immune Cell Therapies (CETI)

Study Record Dates

• First Submitted: May 14, 2018
• First Posted: July 23, 2018
• Study Start: January 24, 2018
• Primary Completion: July 1, 2025
• Study Completion: November 1, 2025
• Last Updated: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)