CytomegalovirusPhase 2NCT01646645
Primary Transplant Donor Derived CMVpp65 Specific T-cells for The Treatment of CMV Infection or Persistent CMV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation
A Phase 2 study testing CMV-pp65 CTLs in people with Cytomegalovirus, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Cytomegalovirus
- What is being tested?
- CMV-pp65 CTLs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jul 2012to 11 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Each patient must satisfy at least one of the following criteria:
- The patient must have a clinically documented condition associated with CMV (e.g. interstitial pneumonia, hepatitis, retinitis, colitis) Or
- 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:
- 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
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- 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
- Stable blood pressure and circulation, not requiring pressor support
- Evidence of adequate cardiac function as demonstrated by EKG and/or echocardiography.
- A life expectancy of at least 3 weeks, even if requiring artificial ventilation.
- There are no age restrictions
Who cannot join
- 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:
- Donors must satisfy the criteria specified in FDA 21 CFR 1271.
- Donors must be typed for HLA-A, B, C and DR
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- Donors must have a hemoglobin value > 10g/dl
- 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
- HTLV/HIV(+) or Hepatitis B or C antigen(+) donors
- Donors who are known CMV seronegative
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065-0009
About this study
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
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.
- Conditions
- Cytomegalovirus
- Being tested
- CMV-pp65 CTLs
- Keywords
- CMVpp65 specific T-cells, Stem Cell Transplantation, 12-086
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMV-pp65 CTLsBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: CMV-pp65 CTLs |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Number of Participants With Toxicities
For the evaluation of toxicities, the NCI Standard Toxicity Scale 4.0 will be employed.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2012 (estimated)
- Study start13 Jul 2012
- Primary completion11 Dec 2019
- Study completion11 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CytomegalovirusStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Atara Biotherapeutics
- Responsible party
- Sponsor
- Investigators
- Susan Prockop, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01646645
- Sponsor's protocol ID
- 12-086
- Status last verified
- Oct 2020
- First submitted
- 18 Jul 2012
- Last updated
- 16 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01646645
- Acronym / sponsor ID
- 12-086
- Conditions
- Cytomegalovirus
- Keywords
- CMVpp65 specific T-cells, Stem Cell Transplantation, 12-086
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Atara Biotherapeutics
- Study start
- 13 Jul 2012 (actual)
- Primary completion
- 11 Dec 2019 (actual)
- Study completion
- 11 Dec 2019 (actual)
- First posted
- 20 Jul 2012 (estimated)
- Results
- Posted 16 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group I | Experimental | Biological: CMV-pp65 CTLsThis 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Each patient must 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
Key exclusion criteria (11 listed)
- 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:
- Donors must satisfy the criteria specified in FDA 21 CFR 1271.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CMV-pp65 CTLsPatients 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. | Biological | Group I |
Primary outcome
Number of Participants With a Complete Response
Time frame: 3 years
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.
Number of Participants With Toxicities
Time frame: 3 years
For the evaluation of toxicities, the NCI Standard Toxicity Scale 4.0 will be employed.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan Prockop, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CMV-pp65 CTLs in people with Cytomegalovirus, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With a Complete Response (time frame: 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2020.