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| Name | Class |
|---|---|
| Atara Biotherapeutics | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group I | Experimental | This is a single-arm non-randomized single institution phase 2 trial, designed to evaluate the therapeutic activity of CMVpp65-CTLs generated from seropositive HSCT donors when adoptively transferred into transplant recipients with persistent CMV infection or viremia. Patients eligible for this trial will be consenting recipients of related or unrelated HSCT who have an active CMV infection or persistent CMV viremia for ≥ 2 weeks despite treatment with anti-viral agents or who cannot be maintained on anti-viral therapy due to treatment related toxicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CMV-pp65 CTLs | Biological | Patients will be treated with CMVpp65-CTLs derived from their transplant donor. These will be patients with CMV seropositive transplant donors who have previously provided leukocytes for generation of CMVpp65-CTL and for whom such CMVpp65-CTL are available. The T-cells to be infused will be selected based on criteria mentioned in section 4.0 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 106 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With a Complete Response | The endpoint of this study is complete response, defined as the clearance of the CMV infection 3-7 weeks following completion of the last cycle of CMV CTLs. The evaluation of treatment efficacy will be assessed separately for patients receiving CMV specific T cells from their transplant donor. | 3 years |
| Number of Participants With Toxicities | For the evaluation of toxicities, the NCI Standard Toxicity Scale 4.0 will be employed. | 3 years |
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Inclusion Criteria:
Each patient must satisfy at least one of the following criteria:
Patient must also satisfy at least one of the following criteria:
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
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
Exclusion Criteria:
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:
6.1.4 Donor Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Susan Prockop, MD | Memorial Sloan Kettering Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065-0009 | United States |
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| Label | URL |
|---|---|
| Memorial Sloan Kettering Cancer Center | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Group I | This is a single-arm non-randomized single institution phase 2 trial, designed to evaluate the therapeutic activity of CMVpp65-CTLs generated from seropositive HSCT donors when adoptively transferred into transplant recipients with persistent CMV infection or viremia. Patients eligible for this trial will be consenting recipients of related or unrelated HSCT who have an active CMV infection or persistent CMV viremia for ≥ 2 weeks despite treatment with anti-viral agents or who cannot be maintained on anti-viral therapy due to treatment related toxicity. CMV-pp65 CTLs: Patients will be treated with CMVpp65-CTLs derived from their transplant donor. These will be patients with CMV seropositive transplant donors who have previously provided leukocytes for generation of CMVpp65-CTL and for whom such CMVpp65-CTL are available. The T-cells to be infused will be selected based on criteria mentioned in section 4.0 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 106 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 22, 2019 |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Group I | This is a single-arm non-randomized single institution phase 2 trial, designed to evaluate the therapeutic activity of CMVpp65-CTLs generated from seropositive HSCT donors when adoptively transferred into transplant recipients with persistent CMV infection or viremia. Patients eligible for this trial will be consenting recipients of related or unrelated HSCT who have an active CMV infection or persistent CMV viremia for ≥ 2 weeks despite treatment with anti-viral agents or who cannot be maintained on anti-viral therapy due to treatment related toxicity. CMV-pp65 CTLs: Patients will be treated with CMVpp65-CTLs derived from their transplant donor. These will be patients with CMV seropositive transplant donors who have previously provided leukocytes for generation of CMVpp65-CTL and for whom such CMVpp65-CTL are available. The T-cells to be infused will be selected based on criteria mentioned in section 4.0 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 106 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. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With a Complete Response | The endpoint of this study is complete response, defined as the clearance of the CMV infection 3-7 weeks following completion of the last cycle of CMV CTLs. The evaluation of treatment efficacy will be assessed separately for patients receiving CMV specific T cells from their transplant donor. | Posted | Count of Participants | Participants | 3 years |
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| Primary | Number of Participants With Toxicities | For the evaluation of toxicities, the NCI Standard Toxicity Scale 4.0 will be employed. | Posted | Number | participants | 3 years |
|
3 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group I | This is a single-arm non-randomized single institution phase 2 trial, designed to evaluate the therapeutic activity of CMVpp65-CTLs generated from seropositive HSCT donors when adoptively transferred into transplant recipients with persistent CMV infection or viremia. Patients eligible for this trial will be consenting recipients of related or unrelated HSCT who have an active CMV infection or persistent CMV viremia for ≥ 2 weeks despite treatment with anti-viral agents or who cannot be maintained on anti-viral therapy due to treatment related toxicity. CMV-pp65 CTLs: Patients will be treated with CMVpp65-CTLs derived from their transplant donor. These will be patients with CMV seropositive transplant donors who have previously provided leukocytes for generation of CMVpp65-CTL and for whom such CMVpp65-CTL are available. The T-cells to be infused will be selected based on criteria mentioned in section 4.0 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 106 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. | 18 | 58 | 11 | 58 | 28 | 58 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acidosis | Metabolism and nutrition disorders | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
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| Catheter related infection | Infections and infestations | Systematic Assessment |
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| Death NOS | General disorders | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
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| Hepatobiliary disorders - Other, specify | Hepatobiliary disorders | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Neutrophil count decreased | Investigations | Systematic Assessment |
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| Renal and urinary disorders - Other, specify | Renal and urinary disorders | Systematic Assessment |
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| Thromboembolic event | Vascular disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Platelet count decreased | Investigations | Systematic Assessment |
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| Lymphocyte count decreased | Investigations | Systematic Assessment |
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| Hypophosphatemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Neutrophil count decreased | Investigations | Systematic Assessment |
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| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
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| White blood cell decreased | Investigations | Systematic Assessment |
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| Hypermagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
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| Blood bilirubin increased | Investigations | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
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| Alkaline phosphatase increased | Investigations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Susan Prockop | Memorial Sloan Kettering Cancer Center | 212-639-6715 | prockops@mskcc.org |
| Oct 8, 2020 |
| Prot_SAP_000.pdf |
| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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