Clinical trial NCT01646645: Primary Transplant Donor Derived CMVpp65 Specific T-cells for The Treatment of CMV Infection or Persistent CMV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation
Official title: A Phase II Trial of Primary Transplant Donor Derived CMVpp65 Specific T-cells for The Treatment of CMV Infection or Persistent CMV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cytomegalovirus
Keywords: CMVpp65 specific T-cells
Stem Cell Transplantation
12-086
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Atara Biotherapeutics
First posted: 2012-07-20
Enrollment: 58
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see how well transfusions of T-cells work in treating CMV. T-cells 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.


Eligibility criteria: 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 c. 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 \[corrected creatinine clearance ≤ 60 ml/min/1.73 m2 or serum creatinine \> 2 mg/dl\]) Patient has CMV specific T-cells from the donor of his/her HSCT available. 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

Exclusion Criteria:

* Patients requiring high doses of glucocorticosteroids (≥ 0.3 mg/kg prednisone or its equivalent) 2. Patients who are moribund 3. 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.

3.4. Patients who are pregnant 6.1.3 Donor Inclusion Criteria 6.1.3a Donors in Group 1 (Historical Donors) Donors in Group 1 (Section 5.1) would have already been determined to be eligible and will have donated blood or leukocytes to establish CMV-specific T-cells under IRB # 05-065, 07-055, 95-024, or 11-130. There are no additional eligibility requirements for these donors.

6.1.3b Donors in Groups 2 \& 3 (Prospective and Volunteer Donors)

Transplant donors and healthy HLA typed volunteers who agree to provide T-cells for Third-party donation (section 5.1, Groups 2 and 3) will need to meet the following eligibility requirements prior to donation:

1. Donors must satisfy the criteria specified in FDA 21 CFR 1271.
2. Donors must be typed for HLA-A, B, C and DR
3. Donors must have a hemoglobin value \> 10g/dl
4. Donors must be capable of undergoing, at least, a single standard 2 blood volume leukapheresis or a donation of one unit of whole blood

6.1.4 Donor Exclusion Criteria

1. HTLV/HIV(+) or Hepatitis B or C antigen(+) donors
2. Donors who are known CMV seronegative

Primary outcomes:
measure: Number of Participants With a Complete Response
timeFrame: 3 years
measure: Number of Participants With Toxicities
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Susan Prockop, MD
role: PRINCIPAL_INVESTIGATOR
References: