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

November 2, 2022 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
117

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
  • CTX
  • Cy
Drug: Mycophenolate mofetil
Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Other Names:
  • CellCept
  • MMF
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
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
  • CTX
  • Cy
Drug: Mycophenolate mofetil
Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Other Names:
  • CellCept
  • MMF
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 21, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 22, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 3, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 2, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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