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Myelodysplastic SyndromePhase 2NCT02556931

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

A Phase 2 study testing Fludarabine, Cyclophosphamide and Total body irradiation in people with Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Any age
What is being tested?
Fludarabine, Cyclophosphamide and Total body irradiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
117 participants
Where
1 siteUnited States
Study dates
Dec 2015to Apr 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • Pregnancy or active breastfeeding
  • Uncontrolled active infection
  • Previous allogeneic transplant
  • Active extramedullary leukemia or active central nervous system (CNS) malignant disease

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21287

Other trials in United States

About this study

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

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.

Read the 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.

Keywords
immunosuppression, nonmyeloablative, non-myeloablative, allogeneic, tacrolimus, peripheral blood, cyclophosphamide, mycophenolate mofetil
Medical subject headings
Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Prolymphocytic, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myeloproliferative Disorders, Multiple Myeloma, Neoplasms, Plasma Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FludarabineDrug

    Also called Fludara

    Days -6 through -2: 30 mg/m^2 IV daily

  • CyclophosphamideDrug

    Also called Cytoxan, Cy, CTX

    Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily

  • Total body irradiationRadiation

    Also called TBI

    Day -1: 200 cGy in a single fraction

  • TacrolimusDrug

    Also called Prograf, FK506, FK-506

    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.

  • Mycophenolate mofetilDrug

    Also called MMF, CellCept

    Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)

Study groups in NCT02556931
Study groupRoleWhat they receive
PBSCT D90ExperimentalNon-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.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Drug: Tacrolimus; Drug: Mycophenolate mofetil
PBSCT D60ExperimentalNon-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.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Drug: Tacrolimus; Drug: Mycophenolate mofetil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Who Are Able to Stop Prophylactic Tacrolimus (D90 Cohort)

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

    Measured: Day 90

  2. Percentage of Participants Who Are Able to Stop Prophylactic Tacrolimus (D60 Cohort)

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

    Measured: Day 60

Secondary outcomes (20)

  1. Number of Participants With Grades III-IV Acute GVHD, Days 90-180 (D90)

    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.

    Measured: Between Day 90 and Day 180

  2. Number of Participants With Grades III-IV Acute GVHD, Days 60-180 (D60)

    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.

    Measured: Between Day 60 and Day 180

  3. Number of Participants With Chronic GVHD, Days 90-180 (D90)

    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.

    Measured: Between Day 90 and Day 180

  4. Number of Participants With Chronic GVHD, Days 60-180 (D60)

    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.

    Measured: Between Day 60 and Day 180

  5. Number of Participants Who Experience Graft Failure, Days 90-180 (D90)

    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.

    Measured: Between Day 90 and Day 180

  6. Number of Participants Who Experience Graft Failure, Days 60-180 (D60)

    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.

    Measured: Between Day 60 and Day 180

  7. Number of Participants Who Experience Disease Relapse, Days 90-180 (D90)

    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.

    Measured: Between Day 90 and Day 180

  8. Number of Participants Who Experience Disease Relapse, Days 60-180 (D60)

    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.

    Measured: Between Day 60 and Day 180

  9. Number of Participants Who Experience Non-relapse Mortality, Days 90-180 (D90)

    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.

    Measured: Between Day 90 and Day 180

  10. Number of Participants Who Experience Non-relapse Mortality, Days 60-180 (D60)

    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.

    Measured: Between Day 60 and Day 180

  11. Number of Participants Who Experience Grades III-IV GVHD, Day 360 (D90)

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

    Measured: Day 360

  12. Number of Number of Participants Who Experience Grades III-IV GVHD, Day 360 (D60)

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

    Measured: Day 360

  13. Number of Number of Participants With Severe Chronic GVHD, Day 360 (D90)

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

    Measured: Day 360

  14. Number of Number of Participants With Severe Chronic GVHD, Day 360 (D60)

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

    Measured: Day 360

  15. Number of Number of Participants Who Experience Graft Failure, Day 360 (D90)

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

    Measured: Day 360

  16. Number of Number of Participants Who Experience Graft Failure, Day 360 (D60)

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

    Measured: Day 360

  17. Number of Participants Who Experience Relapse, Day 360 (D90)

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

    Measured: Day 360

  18. Number of Participants Who Experience Relapse, Day 360 (D60)

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

    Measured: Day 360

  19. Number of Participants Who Experience Non-relapse Mortality, Day 360 (D90)

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

    Measured: Day 360

  20. Number of Participants Who Experience Non-relapse Mortality, Day 360 (D60)

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

    Measured: Day 360

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Sep 2015 (estimated)
  2. Study startDec 2015
  3. Primary completionApr 2021
  4. Study completionApr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
117 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02556931
Sponsor's protocol ID
J15165
Other IDs
IRB00080399, P01CA015396
Status last verified
Nov 2022
First submitted
21 Sep 2015
Last updated
3 Nov 2022
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fludarabine, Cyclophosphamide and Total body irradiation in people with Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Are Able to Stop Prophylactic Tacrolimus (D90 Cohort) (time frame: Day 90). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02556931.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2022.

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