Trial Outcomes & Findings for Primary Transplant Donor Derived CMVpp65 Specific T-cells for The Treatment of CMV Infection or Persistent CMV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation (NCT NCT01646645)
NCT ID: NCT01646645
Last Updated: 2020-12-16
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
58 participants
Primary outcome timeframe
3 years
Results posted on
2020-12-16
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
58
|
|
Overall Study
COMPLETED
|
28
|
|
Overall Study
NOT COMPLETED
|
30
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
No Treated
|
1
|
|
Overall Study
Inevaluable Donor
|
29
|
Baseline Characteristics
Primary Transplant Donor Derived CMVpp65 Specific T-cells for The Treatment of CMV Infection or Persistent CMV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation
Baseline characteristics by cohort
| Measure |
Group I
n=58 Participants
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.
|
|---|---|
|
Age, Continuous
|
49 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
43 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
40 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
58 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 yearsThe 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.
Outcome measures
| Measure |
Group I
n=58 Participants
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.
|
|---|---|
|
Number of Participants With a Complete Response
Participants With Complete Response
|
8 Participants
|
|
Number of Participants With a Complete Response
Participants Without Complete Response
|
50 Participants
|
PRIMARY outcome
Timeframe: 3 yearsFor the evaluation of toxicities, the NCI Standard Toxicity Scale 4.0 will be employed.
Outcome measures
| Measure |
Group I
n=58 Participants
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.
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|---|---|
|
Number of Participants With Toxicities
|
58 participants
|
Adverse Events
Group I
Serious events: 11 serious events
Other events: 28 other events
Deaths: 18 deaths
Serious adverse events
| Measure |
Group I
n=58 participants at risk
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.
|
|---|---|
|
Metabolism and nutrition disorders
Acidosis
|
1.7%
1/58 • 3 years
|
|
Investigations
Alanine aminotransferase increased
|
1.7%
1/58 • 3 years
|
|
Investigations
Aspartate aminotransferase increased
|
1.7%
1/58 • 3 years
|
|
Infections and infestations
Catheter related infection
|
3.4%
2/58 • 3 years
|
|
General disorders
Death NOS
|
10.3%
6/58 • 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
1.7%
1/58 • 3 years
|
|
Injury, poisoning and procedural complications
Fall
|
1.7%
1/58 • 3 years
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify
|
1.7%
1/58 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
12.1%
7/58 • 3 years
|
|
Investigations
Neutrophil count decreased
|
1.7%
1/58 • 3 years
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, specify
|
1.7%
1/58 • 3 years
|
|
Vascular disorders
Thromboembolic event
|
1.7%
1/58 • 3 years
|
Other adverse events
| Measure |
Group I
n=58 participants at risk
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.
|
|---|---|
|
Investigations
Platelet count decreased
|
34.5%
20/58 • 3 years
|
|
Investigations
Lymphocyte count decreased
|
31.0%
18/58 • 3 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
25.9%
15/58 • 3 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
22.4%
13/58 • 3 years
|
|
Investigations
Neutrophil count decreased
|
22.4%
13/58 • 3 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
20.7%
12/58 • 3 years
|
|
Investigations
White blood cell decreased
|
17.2%
10/58 • 3 years
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
13.8%
8/58 • 3 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
12.1%
7/58 • 3 years
|
|
Investigations
Aspartate aminotransferase increased
|
10.3%
6/58 • 3 years
|
|
Investigations
Blood bilirubin increased
|
10.3%
6/58 • 3 years
|
|
Investigations
Alanine aminotransferase increased
|
8.6%
5/58 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
8.6%
5/58 • 3 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
6.9%
4/58 • 3 years
|
|
Investigations
Alkaline phosphatase increased
|
5.2%
3/58 • 3 years
|
Additional Information
Dr. Susan Prockop
Memorial Sloan Kettering Cancer Center
Phone: 212-639-6715
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place