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Autologous Cytomegalovirus (CMV)-Specific Cytotoxic T Cells for Cytomegalovirus (CMV) Reactivation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02210065
Recruitment Status : Completed
First Posted : August 6, 2014
Last Update Posted : May 22, 2019
Sponsor:
Collaborator:
Miltenyi Biotec GmbH
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE August 4, 2014
First Posted Date  ICMJE August 6, 2014
Last Update Posted Date May 22, 2019
Actual Study Start Date  ICMJE March 3, 2015
Actual Primary Completion Date May 13, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 4, 2014)
  • Time to Non-Relapse Mortality [ Time Frame: 6 months ]
    Non-relapse mortality defined as death because of causes other than relapse of the underlying hematological malignancy. Time to non-relapse mortality defined as time to non-relapse mortality from date of stem cell transplantation. Treatment failure event defined as death, graft failure, or grade 3-4 toxicity secondary to CTL infusion in 6 months after CTL infusion. The Bayesian method of Thall, et used to monitor non-relapse mortality.
  • Success Rate of Cytotoxic T Cells [ Time Frame: 28 days ]
    Treatment considered a success if the patient does not require initiation of cytomegalovirus (CMV) anti-viral therapy.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02210065 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous Cytomegalovirus (CMV)-Specific Cytotoxic T Cells for Cytomegalovirus (CMV) Reactivation
Official Title  ICMJE The Pre-Emptive Use of Recipient-Derived Autologous Cytomegalovirus (CMV)-Specific Cytotoxic T Cells for Cytomegalovirus (CMV) Reactivation After Allogeneic Stem Cell Transplantation
Brief Summary The goal of this clinical research study is to learn if giving cytotoxic T lymphocytes (CTLs) can help control CMV when it reactivates (becomes active again) in patients who receive an allogeneic stem cell transplant. Researchers also want to learn about the safety of giving CTLs to patients who have had a stem cell transplant.
Detailed Description

The CTLs:

Blood (about 34 tablespoons) will be drawn 1 time. The blood will be frozen and stored in a laboratory at MD Anderson for future use to make the CTLs. If CMV comes back after your transplant, the blood will be used to create CTLs. To create CTLs, blood cells are grown in the laboratory and trained to kill CMV. If the blood is not used to make the CTLs within 3 years, it will be destroyed.

CTL Administration:

If your CMV becomes active after your stem cell transplant, you will receive the CTLs through a needle in your vein over 1-5 minutes one time, within 72 hours after CMV becomes active again. Before you receive the CTLs, you will receive Benadryl (diphenhydramine) and Tylenol (acetaminophen) by mouth to help reduce the risk of side effects. This can be done in either the hospital (if not yet discharged after your transplant) or in the outpatient clinic (if you are discharged).

Your vital signs will be monitored at the end of the infusion, and then at 30 and 60 minutes after the infusion. Your oxygen level will be measured by pulse oximetry. For this test, a clothespin-shaped clip will be placed on your finger for at least 30 minutes. If you are an outpatient, you will remain in the clinic for at least 1 hour after the CTL infusion.

If the CMV does not become active again after your stem cell transplant, you will not receive the CTL infusion.

Study Visits:

If the CMV does not become active again after your stem cell transplant, you will not receive the CTL infusion and your follow-up care will be done as per post-transplant standard of care.

If you receive the CTL infusion, you will have the tests/procedures listed below.

Within 48 hours before the CTL infusion:

  • You will have a physical exam.
  • Blood (about 6 tablespoons) will be drawn for routine tests and to check your kidney and liver function. Part of blood draw will be used for a pregnancy test for women who are able to become pregnant. To take part in this study, you must not be pregnant.

Once a week for 4 weeks, blood (about 4-8 tablespoons) will be drawn to check the level of CMV infection in your body. This may be done more often, if you doctor thinks it is needed.

About 1, 2, 3, and 4 weeks, and then about 3, 6, and 12 months after the CTL infusion:

  • You will have a physical exam.
  • Blood (about 4 tablespoons) will be drawn for routine tests and to check your kidney and liver function.

Blood (about 4 tablespoons) will be drawn for tests to learn more about the way the CTLs are working and how long they last in the body. This blood will be drawn before the CTL infusion, and then about 2 weeks, 4 weeks, 3 months, and 6 months after the CTL infusion. If possible, the blood needed for these tests will be collected during blood draws for routine tests so that no additional needle sticks will be needed.

Follow-Up Visits:

Once a week for 6 weeks, and then about 3, 6, 9, and 12 months after the CTL infusion, you will be checked for signs of graft-versus-host disease (GVHD) at every clinic visit. You were told about GVHD at the time of being prepared for transplant.

Length of Study:

Your participation on this study will end after your last follow-up visit about 12 months after the CTL infusion.

This is an investigational study. The use of CTLs to treat CMV infection is not FDA approved. At this time, CTLs are only being used to treat infections in research studies.

Up to 105 patients will take part in this study. All will be enrolled at MD Anderson.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Lymphoma
Intervention  ICMJE Biological: Cytomegalovirus (CMV)-Specific Cytotoxic T Cells (CTLs)
CTL product given as single infusion within 72 hours of CMV reactivation. CTL dose infused will be at a maximum dose of 10e5 viable CD3+ T cells/kg.
Study Arms  ICMJE Experimental: Cytomegalovirus (CMV)-Specific Cytotoxic T Cells (CTLs)
CTL product given as single infusion within 72 hours of CMV reactivation. CTL dose infused will be at a maximum dose of 10e5 viable CD3+ T cells/kg.
Intervention: Biological: Cytomegalovirus (CMV)-Specific Cytotoxic T Cells (CTLs)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 26, 2017)
6
Original Estimated Enrollment  ICMJE
 (submitted: August 4, 2014)
105
Actual Study Completion Date  ICMJE May 13, 2019
Actual Primary Completion Date May 13, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. STEP 1: Within 30 days of study entry: Patients with a history of bone marrow disorders including hematological malignancies and aplastic anemia, Myelodysplastic Syndrome (MDS) and Myeloproliferative disorder (MPD) planning to undergo allogeneic HSCT with reduced intensity or myeloablative conditioning regimens.
  2. Disease status must be complete remission by standard criteria for Lymphoma and Acute Leukemia patients.
  3. Patients with Myelodysplastic Syndrome (MDS) and Myeloproliferative Disorder (MPD) must have <5% blasts in the bone marrow.
  4. Patients with T Cell ALL must be in complete remission and MRD negative (-) by flow cytometry and molecular studies.
  5. Patients >/= 18 years of age.
  6. Karnofsky greater than or equal to 80%.
  7. CMV seropositive.
  8. Donor is either matched related, matched unrelated, mismatched unrelated, or haploidentical. Cord blood recipients are also eligible.
  9. Hgb greater than 10 g/L.
  10. Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent.
  11. Negative pregnancy test in female patients of childbearing potential.
  12. STEP 2: Eligibility at time of generating and infusing CMV-specific cytotoxic T cells (adoptive immunotherapy): CMV reactivation defined as CMV DNAemia >/= 137 copies/ml.
  13. Evidence of neutrophil engraftment defined as the absolute neutrophil count (ANC)> 0.5 X 10^3/for 3 consecutive days.
  14. Clinical status to allow tapering of steroids to less than 0.5 mg/kg/day prednisone or equivalent.
  15. Negative pregnancy test in female patients of childbearing potential.

Exclusion Criteria:

  1. STEP 1: Within 30 days of study entry: T cell leukemia or lymphoma.
  2. CMV seronegative.
  3. Positive for HIV, HBV, HCV, HTLV1 and/or HTLV2.
  4. STEP 2: Eligibility at time of generating and infusing CMV-specific cytotoxic T cells (adoptive immunotherapy): Documented CMV end-organ disease.
  5. Patients receiving ATG, or Campath within 28 days of CMV reactivation.
  6. Patients with other uncontrolled infections. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to generating CTLs. For fungal infections patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to generating CTLs. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
  7. Patients who have received donor lymphocyte infusion (DLI) within 28 days.
  8. Patients with active acute GVHD grades II-IV.
  9. Active and uncontrolled relapse of malignancy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02210065
Other Study ID Numbers  ICMJE 2013-0620
NCI-2014-02335 ( Registry Identifier: NCI CTRP )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE Miltenyi Biotec GmbH
Investigators  ICMJE
Principal Investigator: Betul Oran, MD M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date May 2019

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