Primary Transplant or Third Party Donor Derived CMVpp65 Specific T-cells for The Treatment of CMV Infection or Persistent CMV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation

This study is currently recruiting participants.
Verified November 2013 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01646645
First received: July 18, 2012
Last updated: November 12, 2013
Last verified: November 2013

July 18, 2012
November 12, 2013
July 2012
July 2015   (final data collection date for primary outcome measure)
  • efficacy CMV specific T cells [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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 1) patients receiving CMV specific T cells from their transplant donor and 2) patients receiving CMV specific T cells from a matched third party donor.
  • safety of CMV specific T cells [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    For the evaluation of toxicities, the NCI Standard Toxicity Scale 4.0 will be employed.
Same as current
Complete list of historical versions of study NCT01646645 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Primary Transplant or Third Party Donor Derived CMVpp65 Specific T-cells for The Treatment of CMV Infection or Persistent CMV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation
A Phase II Trial of Primary Transplant or Third Party 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.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Cytomegalovirus
Genetic: CMV-pp65 CTLs

In this phase II trial, patients in group I and group II will be treated at dose of 1 x 106 CMVpp65- CTL/kg/dose/week for 3 weeks (+/- 20% variability of total dose). 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.

If the planned dose of CMV peptide sensitized T-cells is not achieved, but the cells generated exhibit required levels of CMV specific cytotoxic activity and meet all other release criteria, the Tcell product may be administered at a lower dose level. In certain cases, in order to avoid refreezing of the final product to achieve a specific dose level, which may affect viability, variability of each dose may exceed +/-20%. In such cases, care will be given to ensure that the total combined volume of the 3 doses does not exceed the planned dose.

Other Names:
  • Eligible patients who consent to enter this trial and for whom CMV-pp65 CTLs are available, will
  • receive 3 weekly infusions of CMV-pp65 CTLs. The T cells will be administered immediately
  • after thawing. The final product is cryopreserved in a volume of 1-2 ml. This will be drawn up in a
  • sterile syringe containing 30 ml of normosol for intravenous administration and administered by
  • slow intravenous infusion ideally over 1 - 2 minutes.
  • Experimental: Group I
    Group I will include patients treated with CMVpp65-CTLs derived from their transplant donor. These will be patients with CMV seropositive transplant donors who have previously provided leucocytes for generation of CMVpp65-CTL and for whom such CMVpp65-CTL are available.
    Intervention: Genetic: CMV-pp65 CTLs
  • Experimental: Group II
    Group II will include patients treated with CMVpp65-CTLs derived from third party donors. This will include recipients of cord blood HSCT or marrow or peripheral blood HSCT from (i)seronegative donors , or (ii) seropositive donors who do not consent or are unavailable to provide leucocytes for generation of CMVpp65-CTLs.
    Intervention: Genetic: CMV-pp65 CTLs
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
July 2015
July 2015   (final data collection date for primary outcome measure)

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 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]) 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), however, 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

Both
Not Provided
No
Contact: Richard O'Reilly, MD 212-639-5957
Contact: Aisha Hasan, MD 212-639-3267
United States
 
NCT01646645
12-086
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
Not Provided
Principal Investigator: Richard O'Reilly, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP