ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT02556931
Recruitment Status : Active, not recruiting
First Posted : September 22, 2015
Last Update Posted : August 1, 2018
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome Chronic Myelomonocytic Leukemia Small Lymphocytic Lymphoma Chronic Lymphocytic Leukemia Prolymphocytic Leukemia Chronic Myeloid Leukemia Chronic Myeloproliferative Disorders Multiple Myeloma Plasma Cell Neoplasm Plasma Cell Dyscrasia Myelofibrosis Polycythemia Vera Essential Thrombocythemia Plasma Cell Leukemia Drug: Fludarabine Drug: Cyclophosphamide Radiation: Total body irradiation Drug: Tacrolimus Drug: Mycophenolate mofetil Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 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 : December 2015
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : December 2019


Arm Intervention/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 Name: 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 Name: 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 Name: 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 Name: 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




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Incidence of relapse, Day 360 (D90) [ Time Frame: Day 360 ]
    Percentage of participants who experience disease relapse by Day 360. All participants are evaluable.

  18. Incidence of relapse, Day 360 (D60) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Day 360 ]
    Percentage of participants who die for any reason other than disease relapse by Day 360. All participants are evaluable.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02556931


Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Investigators
Principal Investigator: Amy E DeZern, MD 410-502-7208

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02556931     History of Changes
Other Study ID Numbers: J15165
IRB00080399 ( Other Identifier: JHMIRB )
First Posted: September 22, 2015    Key Record Dates
Last Update Posted: August 1, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
immunosuppression
nonmyeloablative
non-myeloablative
allogeneic
tacrolimus
peripheral blood
cyclophosphamide
mycophenolate mofetil

Additional relevant MeSH terms:
Leukemia
Multiple Myeloma
Myelodysplastic Syndromes
Preleukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Primary Myelofibrosis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Polycythemia
Polycythemia Vera
Thrombocytosis
Thrombocythemia, Essential
Neoplasms, Plasma Cell
Plasmacytoma
Myeloproliferative Disorders
Leukemia, Prolymphocytic
Leukemia, Plasma Cell
Paraproteinemias
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders