Trial Search Results

Tocilizumab in Cardiac Transplantation

The purpose of this research study is to see if a study drug called Tocilizumab will, when given with standard anti-rejection medicines, lead to better heart transplantation outcomes at 1 year after the transplant. Specifically, the investigators will evaluate whether taking tocilizumab leads to less rejection, less development of unwanted antibodies, and better heart function.

Stanford is currently not accepting patients for this trial.

Lead Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

Stanford Investigator(s):

Intervention(s):

  • Biological: tocilizumab
  • Biological: Placebo
  • Drug: Standard of Care Triple IS

Phase:

Phase 2

Eligibility


Inclusion Criteria:

Inclusion Criteria- Study Entry

   1. Subject must be able to understand and provide informed consent;

   2. Is a candidate for a primary heart transplant (listed as a heart transplant only);

   3. No desensitization therapy prior to transplant;

   4. Agreement to use contraception: according to the FDA Office of Women's Health
   (http://www.fda.gov/birthcontrol), there are a number of birth control methods that
   are more than 80% effective.

      - Female participants of child-bearing potential must consult with their physician
      and determine the most suitable method(s) from the above referenced list to be
      used for the duration of the study

      - Those who choose oral contraception must agree to use a second form of
      contraception after administration of study drug for a period of 1 year after the
      last dose of study drug.

   5. Mechanical support or investigational drug trials where the intervention ends at the
   time of transplantation are permitted;

   6. In the absence of contraindication, vaccinations should be up to date for hepatitis B,
   influenza, pneumococcal, zoster, and Measles, Mumps, & Rubella (MMR); and

   7. Subjects from areas of endemic coccidioidomycosis are eligible for inclusion but must
   be treated prophylactically with fluconazole or itraconazole.

Inclusion Criteria - Randomization

   1. Recipient of a primary heart transplant;

   2. Negative virtual crossmatch (according to local center criteria);

   3. No desensitization therapy prior to transplant;

   4. Female subjects of childbearing potential must have a negative pregnancy test (serum
   or urine) prior to randomization; and

   5. Agreement to use contraception: according to the FDA Office of Women's Health
   (http://www.fda.gov/birthcontrol), there are a number of birth control methods that
   are more than 80% effective.

      - Female participants of child-bearing potential must consult with their physician
      and determine the most suitable method(s) from the above referenced list to be
      used for the duration of the study

      - Those who choose oral contraception must agree to use a second form of
      contraception after administration of study drug for a period of 1 year after the
      last dose of study drug.

Exclusion Criteria:

Exclusion Criteria Study Entry

   1. Inability or unwillingness of a participant to give written informed consent or comply
   with study protocol;

   2. Candidate for a multiple solid organ or tissue transplants;

   3. Prior history of organ or cellular transplantation requiring ongoing systemic
   immunosuppression;

   4. Currently breast-feeding a child or plans to become pregnant during the timeframe of
   the study follow up period;

   5. History of severe allergic and/or anaphylactic reactions to humanized or murine
   monoclonal antibodies;

   6. Known hypersensitivity to tocilizumab (Actemra®);

   7. Previous treatment with tocilizumab (Actemra®);

   8. Human Immunodeficiency Virus (HIV) positive;

   9. Hepatitis B surface antigen positive;

10. Hepatitis B core antibody positive;

11. Hepatitis C virus positive (HCV+) and has failed to demonstrate sustained viral
   remission for more than 12 months (after anti-viral treatment);

12. Subjects must be tested for latent TB infection (LTBI) within a year prior to
   transplant:

   --Subjects with a positive test for LTBI must complete appropriate therapy for LTBI.

   ---A Subject is considered eligible only if they have a negative test for LTBI within
   one year prior to transplant OR

   ---- if they have completed appropriate LTBI therapy within one year prior to
   transplant.

13. Subjects with a previous history of active Tuberculosis (TB);

14. Subjects with a history of splenectomy;

15. Known active current viral, fungal, mycobacterial or other infections not including
   (left ventricular assist device [LVAD]) driveline infections;

16. History of malignancy less than 5 years in remission.

   --Any history of adequately treated in-situ cervical carcinoma, low grade prostate
   carcinoma, or adequately treated basal or squamous cell carcinoma of the skin will be
   permitted.

17. History of hemolytic-uremic syndrome/ thrombotic thrombocytopenia purpura;

18. History of demyelinating disorders such as:

      - multiple sclerosis,

      - chronic inflammation,

      - demyelinating polyneuropathy.

19. History of gastrointestinal perforations, active inflammatory bowel disease or
   diverticulitis;

20. Any previous treatment with alkylating agents such as chlorambucil or, total lymphoid
   irradiation;

21. Radiation therapy within 3 weeks before enrollment.

   --Enrollment of subjects who require concurrent radiotherapy should be deferred until
   the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.

22. Subjects with a hemoglobin <7.0gm/dL (last measurement within 7 days prior to
   transplant);

23. Subjects with a platelet count of less than 100,000/mm^3 (last measurement within 7
   days prior to transplant);

24. Subjects with an absolute neutrophil count (ANC) of less than 2,000/mm^3 (last
   measurement within 7 days prior to transplant);

25. Subjects with Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT)
   levels >3 x Upper Limit of Normal (ULN);

26. Subjects who are administered or intended to be administered cytolytic or anti-cluster
   of differentiation 25 (CD25) monoclonal antibody agents as induction therapy in the
   immediate post-transplant period;

27. Intent to give the recipient a live vaccine within 30 days prior to randomization;

28. Past or current medical problems or findings from physical examination or laboratory
   testing that are not listed above, which, in the opinion of the investigator, may:

      - pose additional risks from participation in the study,

      - may interfere with the participant's ability to comply with study requirements,
      or

      - that may impact the quality or interpretation of the data obtained from the
      study.

Exclusion Criteria - Randomization

   1. Recipient of multiple solid organ or tissue transplants;

   2. Recipient of ex vivo preserved hearts and hearts donated after cardiac death (DCD);

   3. Currently breast-feeding a child or plans to become pregnant during the timeframe of
   the study follow up period;

   4. History of severe allergic anaphylactic reactions to humanized or murine monoclonal
   antibodies;

   5. Known hypersensitivity to tocilizumab (Actemra®);

   6. Previous treatment with tocilizumab (Actemra®);

   7. HIV positive;

   8. Hepatitis B surface antigen positive;

   9. Hepatitis B core antibody positive;

10. Hepatitis B negative transplant recipient that received a transplant from a hepatitis
   B core antibody positive donor;

11. HCV+ subject(s) who are either untreated or have failed to demonstrate sustained viral
   remission for more than 12 months after anti-viral treatment;

12. Recipient of a hepatitis C virus nucleic acid test (NAT) positive donor organ;

13. Subjects with a previous history of active (TB);

14. Subjects must be tested for latent TB infection (LTBI) within a year prior to
   transplant:

   --Subjects with a positive test for LTBI must complete appropriate therapy for LTBI.

   ---A Subject is considered eligible only if they have a negative test for LTBI within
   one year prior to transplant OR

   ---- if they have completed appropriate LTBI therapy within one year prior to
   transplant.

15. Subjects with a history of splenectomy;

16. Known active current viral, fungal, mycobacterial or other infections, not including
   (left ventricular assist device [LVAD]) driveline infections;

17. History of malignancy less than 5 years in remission.

   --Any history of adequately treated in-situ cervical carcinoma, low grade prostate
   carcinoma, or adequately treated basal or squamous cell carcinoma of the skin will be
   permitted.

18. History of hemolytic-uremic syndrome/ thrombotic thrombocytopenia purpura;

19. History of demyelinating disorders;

20. History of gastrointestinal perforations, active inflammatory bowel disease or
   diverticulitis;

21. Any previous treatment with alkylating agents such as chlorambucil, or with total
   lymphoid irradiation;

22. Radiation therapy within 3 weeks before randomization.

   --Enrollment of subjects who require concurrent radiotherapy should be deferred until
   the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.

23. Subjects with a hemoglobin <7.0gm/dL within 7 days prior to randomization;

24. Subjects with a platelet count of less than 100,000/mm^3 within 7 days prior to
   randomization;

25. Subjects with an absolute neutrophil count (ANC) of less than 2,000/mm^3 within 7 days
   prior to randomization;

26. Subjects with AST or ALT levels >3 x ULN;

27. Subjects who are administered or intended to be administered cytolytic or anti- CD25
   monoclonal antibody agents as induction therapy in the immediate post- transplant
   period;

28. Receipt of a live vaccine within 30 days prior to randomization;

29. Use of investigational drugs after transplantation;

30. Past or current medical problems or findings from physical examination or laboratory
   testing that are not listed above, which, in the opinion of the investigator,

      - may pose additional risks from participation in the study,

      - may interfere with the participant's ability to comply with study requirements,
      or

      - that may impact the quality or interpretation of the data obtained from the
      study.

31. Subjects with known donor-specific antibody at the time of evaluation of antibodies
   for heart transplant surgery (within 6 months).

Ages Eligible for Study

18 Years - 75 Years

Genders Eligible for Study

All

Not currently accepting new patients for this trial

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Helen Luikart, RN
650-724-2883
Not Recruiting