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

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

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.

Study Overview

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

Enrollment (Actual)

117

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.
Days -6 through -2: 30 mg/m^2 IV daily
Other Names:
  • Fludara
Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily
Other Names:
  • Cytoxan
  • CTX
  • Cy
Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Other Names:
  • CellCept
  • MMF
Day -1: 200 cGy in a single fraction
Other Names:
  • TBI
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
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.
Days -6 through -2: 30 mg/m^2 IV daily
Other Names:
  • Fludara
Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily
Other Names:
  • Cytoxan
  • CTX
  • Cy
Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Other Names:
  • CellCept
  • MMF
Day -1: 200 cGy in a single fraction
Other Names:
  • TBI
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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.
Day 60

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Grades III-IV Acute GVHD, Days 90-180 (D90)
Time Frame: Between Day 90 and Day 180
Number 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.
Between Day 90 and Day 180
Number of Participants With Grades III-IV Acute GVHD, Days 60-180 (D60)
Time Frame: Between Day 60 and Day 180
Number 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.
Between Day 60 and Day 180
Number of Participants With Chronic GVHD, Days 90-180 (D90)
Time Frame: Between Day 90 and Day 180
Number 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.
Between Day 90 and Day 180
Number of Participants With Chronic GVHD, Days 60-180 (D60)
Time Frame: Between Day 60 and Day 180
Number 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.
Between Day 60 and Day 180
Number of Participants Who Experience Graft Failure, Days 90-180 (D90)
Time Frame: Between Day 90 and Day 180
Number 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.
Between Day 90 and Day 180
Number of Participants Who Experience Graft Failure, Days 60-180 (D60)
Time Frame: Between Day 60 and Day 180
Number 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.
Between Day 60 and Day 180
Number of Participants Who Experience Disease Relapse, Days 90-180 (D90)
Time Frame: Between Day 90 and Day 180
Number 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.
Between Day 90 and Day 180
Number of Participants Who Experience Disease Relapse, Days 60-180 (D60)
Time Frame: Between Day 60 and Day 180
Number 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.
Between Day 60 and Day 180
Number of Participants Who Experience Non-relapse Mortality, Days 90-180 (D90)
Time Frame: Between Day 90 and Day 180
Number 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.
Between Day 90 and Day 180
Number of Participants Who Experience Non-relapse Mortality, Days 60-180 (D60)
Time Frame: Between Day 60 and Day 180
Number 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.
Between Day 60 and Day 180
Number of Participants Who Experience Grades III-IV GVHD, Day 360 (D90)
Time Frame: Day 360
Number of participants who experience grade III or IV GVHD by Day 360. All participants are evaluable.
Day 360
Number of Number of Participants Who Experience Grades III-IV GVHD, Day 360 (D60)
Time Frame: Day 360
Number of participants who experience grade III or IV GVHD by Day 360. All participants are evaluable.
Day 360
Number of Number of Participants With Severe Chronic GVHD, Day 360 (D90)
Time Frame: Day 360
Number of participants who experience severe chronic GVHD requiring additional immunosuppressive therapy by Day 360. All participants are evaluable.
Day 360
Number of Number of Participants With Severe Chronic GVHD, Day 360 (D60)
Time Frame: Day 360
Number of participants who experience severe chronic GVHD requiring additional immunosuppressive therapy by Day 360. All participants are evaluable.
Day 360
Number of Number of Participants Who Experience Graft Failure, Day 360 (D90)
Time Frame: Day 360
Number of participants who experience graft failure by Day 360. All participants are evaluable.
Day 360
Number of Number of Participants Who Experience Graft Failure, Day 360 (D60)
Time Frame: Day 360
Number of participants who experience graft failure by Day 360. All participants are evaluable.
Day 360
Number of Participants Who Experience Relapse, Day 360 (D90)
Time Frame: Day 360
Number of participants who experience disease relapse by Day 360. All participants are evaluable.
Day 360
Number of Participants Who Experience Relapse, Day 360 (D60)
Time Frame: Day 360
Number of participants who experience disease relapse by Day 360. All participants are evaluable.
Day 360
Number of Participants Who Experience Non-relapse Mortality, Day 360 (D90)
Time Frame: Day 360
Number of participants who die for any reason other than disease relapse by Day 360. All participants are evaluable.
Day 360
Number of Participants Who Experience Non-relapse Mortality, Day 360 (D60)
Time Frame: Day 360
Number of participants who die for any reason other than disease relapse by Day 360. All participants are evaluable.
Day 360

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2015

Primary Completion (Actual)

April 1, 2021

Study Completion (Actual)

April 1, 2021

Study Registration Dates

First Submitted

September 21, 2015

First Submitted That Met QC Criteria

September 21, 2015

First Posted (Estimate)

September 22, 2015

Study Record Updates

Last Update Posted (Actual)

November 3, 2022

Last Update Submitted That Met QC Criteria

November 2, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Other Study ID Numbers

  • J15165
  • P01CA015396 (U.S. NIH Grant/Contract)
  • IRB00080399 (Other Identifier: JHMIRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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