Trial of Third Party Donor Derived CMVpp65 Specific T-cells for The Treatment of CMV Infection or Persistent CMV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation

A Phase II Trial of Third Party Donor Derived CMVpp65 Specific T-cells for The Treatment of CMV Infection or Persistent CMV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation

The purpose of this study is to see how well transfusions of T-cells work in treating CMV. Tcells are a type of white blood cell that helps protect the body from infection. A transfusion is the process by which blood from one person is transferred to the blood of another. In this case, the T-cells are made from the blood of donors who are immune to CMV. The T-cells are then grown and taught to attack the CMV virus in a lab.

Study Overview

• Status: Recruiting
• Conditions: CMV Infection; Persistent CMV Viremia
• Intervention / Treatment: Biological: CMVpp65 Specific T-cells

• Study Type: Interventional
• Enrollment (Estimated): 41
• Phase: Phase 2

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Susan Prockop, MD; Phone Number: 212-639-6715
• Study Contact Backup: Name: Aisha Hasan, MD; Phone Number: 212-639-3267

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Susan Prockop, MD; Phone Number: 212-639-6715
      • Contact: Aisha Hasan, MD; Phone Number: 212-639-3267
      • Principal Investigator: Susan Prockop, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Each patient must satisfy at least one of the following criteria:

  1. The patient must have a clinically documented condition associated with CMV (e.g. interstitial pneumonia, hepatitis, retinitis, colitis) Or
  2. The patient must have microbiological evidence of CMV viremia or tissue invasion as attested by viral culture, or detection of levels of CMV DNA in the blood or body fluids consistent with CMV infection.

• Patient must also satisfy at least one of the following criteria:

  1. The patient's CMV infection is clinically progressing or CMV viremia is persistent or increasing (as evidenced by quantitation of CMV DNA in the blood) despite two weeks induction therapy with antiviral drugs.

     Or

  2. The patient has developed CMV viremia as attested by viral culture, or detection of levels of CMV DNA in blood or body fluids while receiving prophylactic doses of antiviral drugs to prevent CMV infection post transplant.

     Or

  3. The patient is unable to sustain treatment with antiviral drugs due to drug associated toxicities (e.g. myelosuppression [ANC< 1000μl/ml without GCSF support] or nephrotoxicity [corrected creatinine clearance ≤ 60 ml/min/1.73 m^2 or serum creatinine > 2 mg/dl]) CMV infections are life threatening, and may involve multiple organ systems such as the lungs, liver, gastrointestinal tract, hematopoietic and central nervous systems. Antiviral drugs used for treatment may also compromise renal and hematopoietic function. Therefore, dysfunctions of these organs will not affect eligibility for this protocol.

• Patients must meet the following clinical criteria to receive CMVpp65-CTL infusions

  1. Stable blood pressure and circulation, not requiring pressor support
  2. Evidence of adequate cardiac function as demonstrated by EKG and/or echocardiography.
  3. A life expectancy of at least 3 weeks, even if requiring artificial ventilation.
  4. There are no age restrictions

• Patient must also satisfy at least one of the following criteria:

  1. The patient's HCT donor has not been previously infected by or sensitized to CMV (e.g. a cord blood transplant or a marrow or PBSC transplant from a seronegative donor).
  2. The patient's HCT donor, if seropositive, is either not available or not willing to provide leukocytes for generation of CMV-specific T-cells.
  3. There are CMVpp65-specific T-cells available in appropriate doses in the MSKCC Adoptive Immune T-cell Therapy Bank that are matched with the patient for 1 HLA allele and that exhibit CMVpp65-specific cytotoxic activity that is restricted by an HLA allele shared by the patient

Exclusion Criteria:

• Patients requiring high doses of glucocorticosteroids (≥ 0.3 mg/kg prednisone or its equivalent)
• Patients who are moribund
• Patients with other conditions not related to CMV infection (e.g. uncontrolled bacterial sepsis or invasive fungal infection) which are also life-threatening and which would preclude evaluation of the effects of a T-cell infusion.
• Patients who are pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CMVpp65-CTL T-cells; The T-cells to be infused will be selected from our bank of GMP grade CMVpp65-CTL. T-cells will be administered by bolus intravenous infusion. In this phase II trial, patients will be treated at doses of 1 x 10^6 CMVpp65-CTL/kg/dose/week for 3 weeks. Patients will be observed for the following 3 weeks. Additional 3 week courses of CMVpp65-CTL may be administered if levels of CMV DNA in blood are still detectable despite disease stabilization or improvement.

Biological: CMVpp65 Specific T-cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete response	defined as the clearance of the CMV infection 3-7 weeks following completion of the last cycle of CMV CTLs.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	Will be capturing and tracking Grade 3-5 toxicities which occur within 30 days following an infusion of CMVpp65-specific. For the evaluation of toxicities, the NCI Standard Toxicity Scale 4.0 will be employed.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Susan Prockop, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: May 9, 2014
• First Submitted That Met QC Criteria: May 9, 2014
• First Posted (Estimated): May 13, 2014

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Allogeneic Hematopoietic Stem Cell Transplantation; CMVpp65 Specific T-cells; 14-070
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; DNA Virus Infections; Sepsis; Herpesviridae Infections; Infections; Communicable Diseases; Viremia; Cytomegalovirus Infections
• Other Study ID Numbers: 14-070

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No