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

Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
Overall Status
Completed
CT.gov ID
NCT02556931
Collaborator
National Cancer Institute (NCI) (NIH)
131
Enrollment
1
Location
2
Arms
64
Actual Duration (Months)
2
Patients Per Site Per Month

Study Details

Study Description

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 Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
131 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Challenging to Engraft
Actual Study Start Date :
Dec 1, 2015
Actual Primary Completion Date :
Apr 1, 2021
Actual Study Completion Date :
Apr 1, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: PBSCT D90

Non-myeloablative peripheral blood stem cell transplant (PBSCT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Tacrolimus will be stopped at either Day 90 or Day 180 depending on GVHD status.

Drug: Fludarabine
Days -6 through -2: 30 mg/m^2 IV daily
Other Names:
  • Fludara
  • Drug: Cyclophosphamide
    Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily
    Other Names:
  • Cytoxan
  • Cy
  • CTX
  • Radiation: Total body irradiation
    Day -1: 200 cGy in a single fraction
    Other Names:
  • TBI
  • Drug: Tacrolimus
    Start on Day 5 through either Day 60 or Day 90 depending on cohort assignment. May be continued through Day 180 depending on GVHD status.
    Other Names:
  • Prograf
  • FK506
  • FK-506
  • Drug: Mycophenolate mofetil
    Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
    Other Names:
  • MMF
  • CellCept
  • Experimental: PBSCT D60

    Non-myeloablative peripheral blood stem cell transplant (PBSCT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Tacrolimus will be stopped at either Day 60 or Day 180 depending on GVHD status.

    Drug: Fludarabine
    Days -6 through -2: 30 mg/m^2 IV daily
    Other Names:
  • Fludara
  • Drug: Cyclophosphamide
    Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily
    Other Names:
  • Cytoxan
  • Cy
  • CTX
  • Radiation: Total body irradiation
    Day -1: 200 cGy in a single fraction
    Other Names:
  • TBI
  • Drug: Tacrolimus
    Start on Day 5 through either Day 60 or Day 90 depending on cohort assignment. May be continued through Day 180 depending on GVHD status.
    Other Names:
  • Prograf
  • FK506
  • FK-506
  • Drug: Mycophenolate mofetil
    Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
    Other Names:
  • MMF
  • CellCept
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of participants who are able to stop prophylactic tacrolimus (D90 cohort) [Day 90]

      This outcome measures the feasibility of stopping prophylactic tacrolimus at Day 90.

    2. Percentage of participants who are able to stop prophylactic tacrolimus (D60 cohort) [Day 60]

      This outcome measures the feasibility of stopping prophylactic tacrolimus at Day 60.

    Secondary Outcome Measures

    1. Incidence of grades III-IV acute GVHD, Days 90-180 (D90) [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.

    2. Incidence of grades III-IV acute GVHD, Days 60-180 (D60) [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.

    3. Incidence of chronic GVHD, Days 90-180 (D90) [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.

    4. Incidence of chronic GVHD, Days 60-180 (D60) [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.

    5. Incidence of graft failure, Days 90-180 (D90) [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.

    6. Incidence of graft failure, Days 60-180 (D60) [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.

    7. Incidence of relapse, Days 90-180 (D90) [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.

    8. Incidence of relapse, Days 60-180 (D60) [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.

    9. Incidence of non-relapse mortality, Days 90-180 (D90) [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.

    10. Incidence of non-relapse mortality, Days 60-180 (D60) [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.

    11. Incidence of grades III-IV acute GVHD, Day 360 (D90) [Day 360]

      Percentage of participants who experience grade III or IV acute GVHD by Day 360. All participants are evaluable.

    12. Incidence of grades III-IV acute GVHD, Day 360 (D60) [Day 360]

      Percentage of participants who experience grade III or IV acute GVHD by Day 360. All participants are evaluable.

    13. Incidence of chronic GVHD, Day 360 (D90) [Day 360]

      Percentage of participants who experience chronic GVHD requiring additional immunosuppressive therapy by Day 360. All participants are evaluable.

    14. Incidence of chronic GVHD, Day 360 (D60) [Day 360]

      Percentage of participants who experience chronic GVHD requiring additional immunosuppressive therapy by Day 360. All participants are evaluable.

    15. Incidence of graft failure, Day 360 (D90) [Day 360]

      Percentage of participants who experience graft failure by Day 360. All participants are evaluable.

    16. Incidence of graft failure, Day 360 (D60) [Day 360]

      Percentage of participants who experience graft failure by Day 360. All participants are evaluable.

    17. Incidence of relapse, Day 360 (D90) [Day 360]

      Percentage of participants who experience disease relapse by Day 360. All participants are evaluable.

    18. Incidence of relapse, Day 360 (D60) [Day 360]

      Percentage of participants who experience disease relapse by Day 360. All participants are evaluable.

    19. Incidence of non-relapse mortality, Day 360 (D90) [Day 360]

      Percentage of participants who die for any reason other than disease relapse by Day 360. All participants are evaluable.

    20. Incidence of non-relapse mortality, Day 360 (D60) [Day 360]

      Percentage of participants who die for any reason other than disease relapse by Day 360. All participants are evaluable.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Presence of a suitable related HLA-haploidentical or -matched stem cell donor, or a 10/10 matched unrelated donor

    • Eligible diagnoses: myelodysplastic syndrome (MDS) with at least 1 poor-risk feature; small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) with 17p deletion or with progression < 6 months after a second or greater treatment regimen; T-cell prolymphocytic leukemia (PLL) in partial response or better; interferon- or tyrosine-kinase-refractory chronic myeloid leukemia (CML), or CML in second or subsequent chronic phase; Philadelphia chromosome negative (Ph-) myeloproliferative disease, including myelofibrosis; Multiple myeloma or plasma cell leukemia in partial response or better; Hematologic malignancy in complete remission with minimal residual disease (MRD) detectable by conventional cytogenetics, FISH, flow cytometry, or molecular testing

    • Any previous autologous transplant must have occurred > 3 months ago

    • Left ventricular ejection fraction (LVEF) >= 35%, or shortening fraction > 25%

    • Bilirubin <= 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis)

    • AST and ALT <= 5 x institutional upper limit of normal

    • FEV1 and FVC >= 40% of predicted; if unable to perform pulmonary function testing, oxygen saturation > 92% on room air

    • ECOG performance status <= 2, or Karnofsky/Lansky status >= 60

    Exclusion Criteria:
    • Pregnancy or active breastfeeding

    • Uncontrolled active infection

    • Previous allogeneic transplant

    • Active extramedullary leukemia or active central nervous system (CNS) malignant disease

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreMarylandUnited States21287

    Sponsors and Collaborators

    • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Amy E DeZern, MD, 410-502-7208

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    ClinicalTrials.gov Identifier:
    NCT02556931
    Other Study ID Numbers:
    • J15165
    • IRB00080399
    • P01CA015396
    First Posted:
    Sep 22, 2015
    Last Update Posted:
    Sep 28, 2021
    Last Verified:
    Sep 1, 2021

    Study Results

    No Results Posted as of Sep 28, 2021