CMV Infection, Persistent CMV Viremia
Conditions
Keywords
CMVpp65 Specific T-cells, Allogeneic Hematopoietic Stem Cell Transplantation, 14-070
Brief summary
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.
Interventions
BIOLOGICALCMVpp65 Specific T-cells
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response | 2 years | defined as the clearance of the CMV infection 3-7 weeks following completion of the last cycle of CMV CTLs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With SAE's Possibly Related to Study Treatment | 2 years | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
CMVpp65 Specific T-cells | 77 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not Treated | 8 |
Baseline characteristics
| Characteristic | CMVpp65-CTL T-cells |
|---|---|
| Age, Continuous | 43 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 51 Participants |
| Region of Enrollment United States | 77 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 77 |
| other Total, other adverse events | 9 / 77 |
| serious Total, serious adverse events | 22 / 77 |
Outcome results
Primary
Complete Response
defined as the clearance of the CMV infection 3-7 weeks following completion of the last cycle of CMV CTLs.
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CMVpp65-CTL T-cells | Complete Response | Participants with Complete Response | 20 Participants |
| CMVpp65-CTL T-cells | Complete Response | Participants without Complete Response | 57 Participants |
Secondary
Number of Participants With SAE's Possibly Related to Study Treatment
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.
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CMVpp65-CTL T-cells | Number of Participants With SAE's Possibly Related to Study Treatment | Participants with possibly related SAE | 6 Participants |
| CMVpp65-CTL T-cells | Number of Participants With SAE's Possibly Related to Study Treatment | Participants without possibly related SAE | 71 Participants |