Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Prospective Assessment of Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02934477
Recruitment Status : Recruiting
First Posted : October 17, 2016
Last Update Posted : July 28, 2017
Sponsor:
Collaborators:
National Marrow Donor Program
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Center for International Blood and Marrow Transplant Research

Brief Summary:
This observational study will compare outcomes of a prospectively-enrolled cohort of Hematopoietic Stem Cell Transplant (HCT) recipients with outcomes of a cohort of age-matched historical non-HCT controls. Patients undergoing alloHCT will receive HCT in a US transplant center and be reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) using well-established CIBMTR report forms and data collection procedures as well as a study-specific supplemental form. Data on the historical non-HCT controls will be collected at 14 US academic centers. These centers will provide data on all consecutive patients with PMF, post-ET MF, or post-PV MF referred to their institutions between 2000 and 2012.

Condition or disease Intervention/treatment
Myelofibrosis Other: Hematopoietic Stem Cell Transplant

Detailed Description:

Patients with primary MF (PMF), post-essential thrombocythemia (ET) MF, or post-polycythemia vera (PV) MF, with intermediate-2 or high-risk disease as determined by the DIPSS, and aged ≥55 at the time of DIPSS assessment are eligible for this study. For the allogeneic HCT arm of the HLA-Matched Donor HCT Study, donors must be either 6/6 HLA-matched related donors, defined by Class I (HLA-A and -B) intermediate resolution or high resolution DNA-based typing and Class II (HLA-DRBI) at high resolution DNA-based typing (but not monozygotic twins), OR an 8/8 HLA-A, -B, -C, and -DRB1 at high resolution DNA-based typing matched unrelated donors; both peripheral blood stem cells and bone marrow grafts are allowed, and all conditioning regimen intensities and graph versus host disease (GVHD) prophylaxis regimens are allowed. For the Haploidentical Donor Study, donors must be haploidentical.

This study will target accrual of 650 patients receiving alloHCT, including approximately 225 receiving myeloablative conditioning. Participating centers are expected to provide data for approximately 2,400 patients to form the non-HCT historical control cohort.


Layout table for study information
Study Type : Observational
Estimated Enrollment : 650 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospective Assessment of Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis
Study Start Date : November 2016
Estimated Primary Completion Date : November 2026
Estimated Study Completion Date : October 2027


Group/Cohort Intervention/treatment
Hematopoietic Stem Cell Transplant (HCT)
Patients undergoing alloHCT in a US transplant center and reported to the CIBMTR
Other: Hematopoietic Stem Cell Transplant
This observational study will compare outcomes of prospectively enrolled HCT recipients with outcomes of a cohort of age-matched non-HCT controls.

Non-HCT
Historical non-transplant controls collected from 14 US academic centers. Centers will provide data on all consecutive patients with PMF, post-ET MF, or post-PV MF referred to their institutions between 2000 and 2012.



Primary Outcome Measures :
  1. Compare five year survival [ Time Frame: Five years post transplant ]
    Compare the five-year survival probabilities from DIPSS assessment between the two study arms: alloHCT recipients (arm 1) and non-HCT therapies (ruxolitinib / best supportive care) recipients (arm 2).


Secondary Outcome Measures :
  1. Compare leukemia-free survival [ Time Frame: Five years post transplant ]
    Compare leukemia-free survival at five years from DIPSS assessment date to the date of progression to AML or death from any cause, whichever comes first. Two co-secondary analyses will be conducted, one for all alloHCT patients versus Arm 2 and one for the subset of patients receiving MAC prior to alloHCT versus Arm 2. Observation is censored at the date of last follow-up for patients known to be alive without leukemia. Progression to AML is defined as >20% leukemia blasts in bone marrow or in the peripheral blood.

  2. Cumulative incidences of chronic GVHD [ Time Frame: Five years post transplant ]
    Occurrence of symptoms in any organ system fulfilling the criteria of chronic GVHD. Patients are censored at last follow-up or second transplant.

  3. Cumulative incidences of acute GVHD [ Time Frame: Five years post transplant ]
    Occurrence of grade II, III, and/or IV skin, gastrointestinal, or liver abnormalities fulfilling the Consensus criteria of acute GVHD. Patients are censored at last follow-up or second transplant.

  4. Cumulative incidence of treatment related mortality [ Time Frame: Five years post transplant ]
    Death from any cause in the first 28 days post-transplantation, irrespective of relapse status. Death beyond day +28 will only be considered transplant-related if the disease is in remission. This event will be summarized as a cumulative incidence estimate with relapse/persistence as the competing risk.

  5. The impact of certain patient, disease and HCT related factors on survival in the alloHCT arm. [ Time Frame: Five years post transplant ]
    Evaluation of the impact of response to ruxolitinib therapy, patient age (<65 years vs. >= 65 years, disease duration and DIPSS on overall survival in the alloHCT arm. The time to event in the analyses will start at the time of transplant.

  6. The impact of certain patient, disease and HCT related factors on leukemia free survival in the alloHCT arm. [ Time Frame: Five years post transplant ]
    Evaluation of the impact of response to ruxolitinib therapy, patient age (<65 vs. >= 65 years), disease duration and DIPSS on leukemia free survival in the alloHCT arm. The time to event in the analyses will start at the time of transplant.

  7. The impact of certain patient, disease and HCT related factors on hematopoietic recovery in the alloHCT arm. [ Time Frame: Five years post transplant ]
    Evaluation of the impact of response to ruxolitinib therapy, patient age (<65 vs >=65 years), disease duration and DIPSS on hematopoietic recovery in the alloHCT arm. The time to event in the analyses will start at the time of transplant.

  8. The impact of certain patient, disease and HCT related factors on acute and chronic GVHD in the alloHCT arm. [ Time Frame: Five years post transplant ]
    Evaluation of the impact of response to ruxolitinib therapy, patient age (<65 vs >= 65 years), disease duration and DIPSS on acute and chronic GVHD in the alloHCT arm. The time to event in the analyses will start at the time of transplant.

  9. The impact of certain patient, disease and HCT related factors on treatment related mortality in the alloHCT arm. [ Time Frame: Five years post transplant. ]
    Evaluation of the impact of response to ruxolitinib therapy, patient age (<65 vs >=65 years), disease duration, and DIPSS on treatment related mortality in the alloHCT arm. The time to event in the analyses will start at the time of transplant.

  10. The impact of certain patient, disease and HCT related factors on relapse. [ Time Frame: Five years post transplant. ]
    Evaluation of the impact of response to ruxolitinib therapy, patient age (65 vs >=65 years), disease duration and DIPSS on relapse in the alloHCT arm. The time to event in the analyses will start at the time of transplant.



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.


Layout table for eligibility information
Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with primary MF (PMF), post-essential thrombocythemia (ET) MF, or post-polycythemia vera (PV) MF, with intermediate-2 or high-risk disease as determined by the DIPSS, and aged ≥55 at the time of DIPSS assessment are eligible for this study. For the alloHCT arm of the HLA-Matched Donor HCT Study, donors must be either 6/6 HLA-matched related donors, defined by Class I (HLA-A and -B) intermediate resolution or high resolution DNA-based typing and Class II (HLA-DRBI) at high resolution DNA-based typing (but not monozygotic twins), OR an 8/8 HLA-A, -B, -C, and -DRB1 at high resolution DNA-based typing matched unrelated donors; both peripheral blood stem cells and bone marrow grafts are allowed, and all conditioning regimen intensities and GVHD prophylaxis regimens are allowed. For the Haploidentical Donor Study, donors must be haploidentical.
Criteria

Inclusion Criteria:

  • Patients fulfilling the following criteria will be eligible for inclusion in the study:

    • PMF, post-ET MF, or post-PV MF.
    • Int-2 or high-risk disease as determined by the DIPSS.
    • Age ≥55 at the time of DIPSS assessment.
    • For the alloHCT arm:

      • Donors must be a 6/6 HLA-matched related donors, defined by Class I (HLA-A and -B) intermediate resolution or high resolution DNA-based typing and Class II (HLA-DRBI) at high resolution DNA-based typing (but not monozygotic twins) OR an 8/8 HLA-A, -B, -C, and -DRB1 at high resolution DNA-based typing matched unrelated donor identified through the National Marrow Donor Program (NMDP)/Be The Match. Donors must meet institutional or NMDP/Be The Match selection criteria; there is no age restriction for sibling donors.
      • Both peripheral blood stem cells and bone marrow grafts are allowed.
      • All conditioning regimen intensities are allowed.
      • All GVHD prophylaxis regimens are allowed.
    • Haploidentical donors are allowed in the Haploidentical Donor Study

Exclusion Criteria:

  • Patients with the following criteria will be ineligible for entry into the study:

    • AlloHCT using umbilical cord blood unit(s) or HLA-mismatched adult donors (< 6/6 HLA alleles for related and < 8/8 HLA alleles for unrelated).
    • Overlap syndromes.

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): NCT02934477


Contacts
Layout table for location contacts
Contact: Patricia Steinert, PhD 414-805-0700 psteinert@mcw.edu
Contact: Stephanie Farnia 763-406-8640 sfarnia@nmdp.org

Locations
Layout table for location information
United States, Minnesota
Center for International Blood and Marrow Transplant Research Recruiting
Minneapolis, Minnesota, United States, 55401
Contact: Sue Logan       slogan@nmdp.org   
Sponsors and Collaborators
Center for International Blood and Marrow Transplant Research
National Marrow Donor Program
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Study Chair: Wael Saber, MD Medical College of Wisconsin
Study Chair: Laura Michaelis, MD Medical College of Wisconsin

Additional Information:
CIBMTR  This link exits the ClinicalTrials.gov site

Layout table for additonal information
Responsible Party: Center for International Blood and Marrow Transplant Research
ClinicalTrials.gov Identifier: NCT02934477     History of Changes
Other Study ID Numbers: 16-CMS-MF
U24CA076518 ( U.S. NIH Grant/Contract )
First Posted: October 17, 2016    Key Record Dates
Last Update Posted: July 28, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Center for International Blood and Marrow Transplant Research:
Myelofibrosis
Hematopoietic Stem Cell Transplant
Medicare
Additional relevant MeSH terms:
Layout table for MeSH terms
Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases