Adoptive Cord Blood Immunotherapy for EBV, CMV, BKV and Adenovirus Reactivation/Infection or Prophylaxis
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|ClinicalTrials.gov Identifier: NCT03594981|
Recruitment Status : Recruiting
First Posted : July 23, 2018
Last Update Posted : February 3, 2023
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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.
|Condition or disease||Intervention/treatment||Phase|
|Viral Infection||Biological: CMV/AdV /EBV/BKV specific T cells||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Adoptive Cord Blood ImmunotHerapy Using Expanded Cord Blood T Cells for EBV, CMV, BKV and Adenovirus Reactivation/Infection or ProphylaxiS|
|Actual Study Start Date :||January 24, 2018|
|Estimated Primary Completion Date :||July 2024|
|Estimated Study Completion Date :||November 2025|
Experimental: CMV/AdV /EBV/BKV specific T cells
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
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.
- Number of participants with investigational product-related adverse events as assessed by CTCAE v4.03 [ Time Frame: 45 days for toxicity ]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.
- Impact of CMV/AdV /EBV/BKV specific T cells will be measured by existence of cells in the system. [ Time Frame: 12 months ]To evaluate the impact of CTLs on CMV/AdV /EBV/BKV -specific T-lymphocyte immune reconstitution. The impact will be evaluated by the number of months/years of cell survival.
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|Ages Eligible for Study:||Child, Adult, Older Adult|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03594981
|Contact: Allistair Abraham, MD||202-476-5772||AAbraham@childrensnational.org|
|Contact: Fahmida Hoq, MBBS, MSemail@example.com|
|United States, District of Columbia|
|Children's National Health System||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: Fahmida Hoq, MBBS, MS 202-476-3634 firstname.lastname@example.org|
|Principal Investigator: Allistair Abraham, MD|
|United States, Texas|
|M.D. Anderson Cancer Center (MDACC)||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Amanda Olson, MD|
|Principal Investigator: Amanda Olson, MD|
|Responsible Party:||Catherine Bollard, Director, Center for Cancer and Immunology/ Center for Emerging Technologies in Immune Cell Therapies (CETI), Children's National Research Institute|
|Other Study ID Numbers:||
|First Posted:||July 23, 2018 Key Record Dates|
|Last Update Posted:||February 3, 2023|
|Last Verified:||February 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|