Clinical Trial: Shorter Course Tacro After NMA, Related Donor PBSCT With High-dose Posttransplant Cy for Hard-to-Engraft Malignancies

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase II Study of Shortened-duration Tacrolimus Following Nonmyeloablative Peripheral Blood Stem Cell Transplant With High-dose Posttransplantation Cyclophosphamide in Malignancies That Are Challengin

Brief Summary: To see if it is possible to use short-duration tacrolimus after a peripheral blood stem cell transplant in certain malignancies that are considered difficult to engraft.

Detailed Summary: The main goal is to learn whether a drug called tacrolimus, which is an immune-lowering drug (an immunosuppressant) given after transplant to help prevent certain complications, can be given safely for a shorter period of time than it has been in the past. The experiences with immunosuppression duration with other allogeneic HSCT platforms cannot be directly extrapolated to the high-dose posttransplantation cyclophosphamide platform (another type of immunosuppressant given after transplant to help prevent GVHD). There are presently no published data on the minimum required duration of tacrolimus after nonmyeloablative HSCT that includes high-dose Cy as part of postgrafting immunosuppression. The effectiveness of high-dose posttransplantation Cy in GVHD prevention, however, permits the investigation of this question. At the present time there are few or no cures for diseases studied on this trial outside of a bone marrow or peripheral blood transplant. The peripheral blood for this transplant comes from a relative who is a half-match or "haplo" match to the participant. Possible donors include parents, siblings, and children. In order to help the bone marrow grow, or "take", inside the body, participants will receive chemotherapy and radiation before the transplant. After the transplant participants will receive high doses of cyclophosphamide (Cytoxan®) along with other medications to lower the immune system, such as tacrolimus. These medications may lower the risk of graft versus host disease (GVHD) and of rejection of the peripheral blood graft.
Sponsor: Sidney Kimmel Comprehensive Cancer Center

Current Primary Outcome:

• Percentage of participants who are able to stop prophylactic tacrolimus (D90 cohort) [ Time Frame: Day 90 ]
  This outcome measures the feasibility of stopping prophylactic tacrolimus at Day 90.
• Percentage of participants who are able to stop prophylactic tacrolimus (D60 cohort) [ Time Frame: Day 60 ]
  This outcome measures the feasibility of stopping prophylactic tacrolimus at Day 60.

Original Primary Outcome: Feasibility of stopping tacrolimus at Day 90 [ Time Frame: Day 90 ]

Current Secondary Outcome:

• Incidence of grades III-IV acute GVHD, Days 90-180 (D90) [ Time Frame: Between Day 90 and Day 180 ]
  Percentage of participants who experience grade III or IV acute GVHD between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.
• Incidence of grades III-IV acute GVHD, Days 60-180 (D60) [ Time Frame: Between Day 60 and Day 180 ]
  Percentage of participants who experience grade III or IV acute GVHD between Day 60 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 60 are evaluable.
• Incidence of chronic GVHD, Days 90-180 (D90) [ Time Frame: Between Day 90 and Day 180 ]
  Percentage of participants who experience chronic GVHD requiring additional immunosuppressive therapy between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.
• Incidence of chronic GVHD, Days 60-180 (D60) [ Time Frame: Between Day 60 and Day 180 ]
  Percentage of participants who experience chronic GVHD requiring additional immunosuppressive therapy between Day 60 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 60 are evaluable.
• Incidence of graft failure, Days 90-180 (D90) [ Time Frame: Between Day 90 and Day 180 ]
  Percentage of participants who experience graft failure between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.
• Incidence of graft failure, Days 60-180 (D60) [ Time Frame: Between Day 60 and Day 180 ]
  Percentage of participants who experience graft failure between Day 60 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 60 are evaluable.
• Incidence of relapse, Days 90-180 (D90) [ Time Frame: Between Day 90 and Day 180 ]
  Percentage of participants who experience disease relapse between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.
• Incidence of relapse, Days 60-180 (D60) [ Time Frame: Between Day 60 and Day 180 ]
  Percentage of participants who experience disease relapse between Day 60 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 60 are evaluable.
• Incidence of non-relapse mortality, Days 90-180 (D90) [ Time Frame: Between Day 90 and Day 180 ]
  Percentage of participants who die for any reason other than disease relapse between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.
• Incidence of non-relapse mortality, Days 60-180 (D60) [ Time Frame: Between Day 60 and Day 180 ]
  Percentage of participants who die for any reason other than disease relapse between Day 60 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 60 are evaluable.
• Incidence of grades III-IV acute GVHD, Day 360 (D90) [ Time Frame: Day 360 ]
  Percentage of participants who experience grade III or IV acute GVHD by Day 360. All participants are evaluable.
• Incidence of grades III-IV acute GVHD, Day 360 (D60) [ Time Frame: Day 360 ]
  Percentage of participants who experience grade III or IV acute GVHD by Day 360. All participants are evaluable.
• Incidence of chronic GVHD, Day 360 (D90) [ Time Frame: Day 360 ]
  Percentage of participants who experience chronic GVHD requiring additional immunosuppressive therapy by Day 360. All participants are evaluable.
• Incidence of chronic GVHD, Day 360 (D60) [ Time Frame: Day 360 ]
  Percentage of participants who experience chronic GVHD requiring additional immunosuppressive therapy by Day 360. All participants are evaluable.
• Incidence of graft failure, Day 360 (D90) [ Time Frame: Day 360 ]
  Percentage of participants who experience graft failure by Day 360. All participants are evaluable.
• Incidence of graft failure, Day 360 (D60) [ Time Frame: Day 360 ]
  Percentage of participants who experience graft failure by Day 360. All participants are evaluable.
• Incidence of relapse, Day 360 (D90) [ Time Frame: Day 360 ]
  Percentage of participants who experience disease relapse by Day 360. All participants are evaluable.
• Incidence of relapse, Day 360 (D60) [ Time Frame: 
  
  

  Original Secondary Outcome:

  • Incidence of grades II-IV acute GVHD, Days 90-180 [ Time Frame: Between Day 90 and Day 180 ]
    Percentage of participants who experience grade II, III, or IV acute GVHD between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.
  • Incidence of grades III-IV acute GVHD, Days 90-180 [ Time Frame: Between Day 90 and Day 180 ]
    Percentage of participants who experience grade III or IV acute GVHD between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.
  • Incidence of chronic GVHD, Days 90-180 [ Time Frame: Between Day 90 and Day 180 ]
    Percentage of participants who experience chronic GVHD between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.
  • Incidence of graft failure, Days 90-180 [ Time Frame: Between Day 90 and Day 180 ]
    Percentage of participants who experience graft failure between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.
  • Incidence of relapse, Days 90-180 [ Time Frame: Between Day 90 and Day 180 ]
    Percentage of participants who experience disease relapse between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.
  • Incidence of non-relapse mortality, Days 90-180 [ Time Frame: Between Day 90 and Day 180 ]
    Percentage of participants who die for any reason other than disease relapse between Day 90 and Day 180. Only participants who are able to stop prophylactic tacrolimus at Day 90 are evaluable.
  • Incidence of grades II-IV acute GVHD, Day 360 [ Time Frame: Day 360 ]
    Percentage of participants who experience grade II, III, or IV acute GVHD by Day 360. All participants are evaluable.
  • Incidence of grades III-IV acute GVHD, Day 360 [ Time Frame: Day 360 ]
    Percentage of participants who experience grade III or IV acute GVHD by Day 360. All participants are evaluable.
  • Incidence of chronic GVHD, Day 360 [ Time Frame: Day 360 ]
    Percentage of participants who experience chronic GVHD by Day 360. All participants are evaluable.
  • Incidence of graft failure, Day 360 [ Time Frame: Day 360 ]
    Percentage of participants who experience graft failure by Day 360. All participants are evaluable.
  • Incidence of relapse, Day 360 [ Time Frame: Day 360 ]
    Percentage of participants who experience disease relapse by Day 360. All participants are evaluable.
  • Incidence of non-relapse mortality, Day 360 [ Time Frame: Day 360 ]
    Percentage of participants who die for any reason other than disease relapse by Day 360. All participants are evaluable.
  
  
  Information By: Sidney Kimmel Comprehensive Cancer Center
  

  Dates:
  Date Received: September 21, 2015
  Date Started: December 2015
  Date Completion: December 2019
  Last Updated: April 11, 2017
  Last Verified: April 2017