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Donor CMV Specific CTLs in Treating CMV Reactivation or Infection in Participants Who Have Undergone Stem Cell Transplant or Solid Organ Transplant

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ClinicalTrials.gov Identifier: NCT03665675
Recruitment Status : Recruiting
First Posted : September 11, 2018
Last Update Posted : January 30, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sumithira Vasu, Ohio State University Comprehensive Cancer Center

Brief Summary:
This trial studies the side effects and how well allogeneic cytomegalovirus-specific cytotoxic T lymphocytes (donor cytomegalovirus [CMV] specific cytotoxic T-lymphocytes [CTLs]) works in treating CMV reactivation or infection in participants who have undergone stem cell transplant or solid organ transplant. White blood cells from donors may be able to kill cancer cells in patients with cytomegalovirus that has come back after a stem cell or solid organ transplant.

Condition or disease Intervention/treatment Phase
Allogeneic Hematopoietic Stem Cell Transplantation Recipient Cytomegalovirus Donor Solid Organ Transplantation Recipient Biological: Allogeneic Cytomegalovirus-Specific Cytotoxic T lymphocytes Early Phase 1

Detailed Description:

PRIMARY OBJECTIVE I. Assess the safety and feasibility of administering high-throughput antigen stimulation/interferon gamma capture system (Miltenyi Biotec, CliniMACS Prodigy System) generated CMV specific- CTLs from haploidentical donors in transplant patients both solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT) with CMV infection despite standard therapy.

OUTLINE:

Participants receive allogeneic cytomegalovirus-specific cytotoxic T lymphocytes intravenously (IV). Participants with partial response, may receive up to 2 additional doses at monthly intervals.

After completion of study treatment, participants are followed up at 1 year.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Haploidentical Donor Cytomegalovirus (CMV) Specific Cytotoxic T-Lymphocytes (CTL) to Treat CMV Reactivation or Infection After Solid Organ and Hematopoietic Stem Cell Transplantation (HCT)
Actual Study Start Date : January 24, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Arm Intervention/treatment
Experimental: Treatment (CMV-specific CTLs)
Participants receive allogeneic cytomegalovirus-specific cytotoxic T lymphocytes IV. Participants with partial response, may receive up to 2 additional doses at monthly intervals.
Biological: Allogeneic Cytomegalovirus-Specific Cytotoxic T lymphocytes
Given intravenously




Primary Outcome Measures :
  1. Incidence of adverse events defined by the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 [ Time Frame: Up to 30 days post infusion ]
    Measured as the proportion of patients with acute (a) graft versus host disease (GvHD) grades III-IV or graft rejection/failure within 30 days of the last dose of cytotoxic T-lymphocytes (CTLs) or grades 3-5 infusion-related adverse events within 7 days of the last does of CTLs or grades 4-5 non-hematological adverse events within 30 days of the last dose of CTLs and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities. Will be calculated by dividing by all evaluable patients and the corresponding 95% confidence intervals will be calculated.

  2. Feasibility defined as identifying a suitable donor within 4 weeks and meeting minimum T cell doses in the final product [ Time Frame: Up to 1 year ]

Secondary Outcome Measures :
  1. Antiviral activity defined as response to viral load [ Time Frame: At day 28 ]
    Complete response, partial response, stable disease or progression will be defined and proportion of each outcome will be calculated.

  2. Persistence of infused CTLs as measured by T cell gene rearrangement and effects on clinical signs of viral infection [ Time Frame: Up to 1 year ]
  3. Overall survival [ Time Frame: From last CTL infusion till death, assessed at 6 and 12 months ]
    Kaplan-Meier survival function will be used to estimate the survival probability.

  4. Risk for chronic GVHD [ Time Frame: At 6 and 12 months post CTL infusion ]
    Survival analysis method will be applied. Time to chronic GVHD will be defined from time of the last CTL infusion to the onset of chronic GVHD, or the last clinical assessment date if no chronic GVHD. Cumulative incidence of chronic GVHD at 6 and 12 months will be estimated.

  5. Systemic infections [ Time Frame: Within 6 months of CTL infusion ]
    Will be reported by etiologic agent, site of disease, date of onset, and severity.

  6. Secondary graft failure [ Time Frame: 30 days post-CTL infusion ]
    Proportion of secondary graft failure for both populations will be assessed at 30 days post CTL infusion will be calculated and 95% confidence intervals will be estimated accordingly.

  7. Effects of cytomegalovirus (CMV) specific-CTL on viral loads assessed by weekly reverse transcriptase-polymerase chain reaction [ Time Frame: Up to 1 year ]
  8. Viral reactivations [ Time Frame: Up to 6 months ]
    Proportion of viral reactivations within 6 months will be calculated and 95% confidence intervals will be estimated accordingly.

  9. Clinical response to CTL infusions [ Time Frame: At 6 weeks and 3 months ]
  10. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0". [ Time Frame: Up to 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients must have solid organ transplant or have received allogeneic hematopoietic stem cell transplant and be greater than 30 days post-transplant at the time of registration.
  • Persistent CMV viremia after standard therapy for >= 7 days with or without proven, probable or possible CMV specific organ involvement.
  • Receipt of an allogeneic HCT using bone marrow, peripheral blood, or umbilical cord stem cells.
  • SOT recipients including but not limited to renal, heart, lung, liver, pancreas, small bowel, and multi-visceral transplants.
  • Treatment of reactivation or infection with CMV: Reactivation is defined as detection of CMV by quantitative polymerase chain reaction (PCR) from the blood. If any patient develops CMV deoxyribonucleic acid (DNA)emia or has clinical evidence of CMV infection (defined as the demonstration of CMV by biopsy specimen from visceral sites by culture or histology) either pre or after CTL infusions, standard treatment with ganciclovir, valganciclovir, cidofovir and/or foscarnet will be initiated per physician discretion. Patients may receive CMV CTLs alone for elevated blood viral loads without evidence of visceral infection.
  • Administration of less than or equal to 0.5 mg/kg/day of prednisone or steroid equivalent.
  • Serum creatinine less than 2 x (upper level of normal (ULN).
  • Available CMV seropositive haploidentical donor who is without evidence infection that would otherwise preclude donation.
  • Negative pregnancy test in female patients if applicable (childbearing potential who have received a reduced intensity conditioning regimen).
  • Written informed consent and/or signed assent line from patient, parent or guardian.
  • DONOR: Donors will be deemed eligible if they are haploidentical matched to the patient and are CMV seropositive, defined as detection of serum CMV IgG. Donor will be screened and determined if acceptable as determined by the full donor evaluation and transplant physician evaluation.

Exclusion Criteria:

  • Receipt of anti-thymocyte globulin (ATG), alemtuzumab, or other T-cell depleting agents within 28 days of screening for enrollment.
  • Receiving > 0.5mg/kg/day of prednisone or steroid equivalent at the time of enrollment.
  • Evidence of uncontrolled infection as follows:

    • Bacterial infections - patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment.
    • Fungal infections - patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment.
    • Patients with hemodynamic instability attributable to bacterial sepsis or new symptoms, worsening physical signs or radiographic findings attributable to concomitant bacterial or fungal infection are excluded. Patients who require ventilator support for CMV pneumonitis are not excluded. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
  • Receipt of donor lymphocyte infusion (DLI) within 28 days.
  • Patients with active acute graft versus host disease (GvHD) grades II-IV requiring > 0.5 mg/kg/day of prednisone or steroid equivalent or T-cell depleting immunosuppression.
  • Acute graft rejection in solid organ transplantation requiring augmented immunosuppression with T-cell depleting agents or steroids as mentioned above.
  • Active and uncontrolled relapse of malignancy.

Information from the National Library of Medicine

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): NCT03665675


Contacts
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Contact: The Ohio State University Comprehensive Cancer Center 800-293-5066 OSUCCCClinicaltrials@osumc.edu
Contact: Nicole Szuminski 614-688-9796 Nicole.Szuminski@osumc.edu

Locations
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United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Sumithira Vasu, MBBS    614-293-3196    Sumithira.Vasu@osumc.edu   
Principal Investigator: Sumithira Vasu, MBBS         
Sponsors and Collaborators
Sumithira Vasu
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Sumithira Vasu, MBBS Ohio State University Comprehensive Cancer Center

Additional Information:
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Responsible Party: Sumithira Vasu, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03665675     History of Changes
Other Study ID Numbers: OSU-17199
NCI-2018-01412 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
OSU-17199 ( Other Identifier: Ohio State University Comprehensive Cancer Center )
P30CA016058 ( U.S. NIH Grant/Contract )
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: January 30, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No