A Study of Bone Marrow Transplantation Using Fully-Matched Relatives as Donors for Patients With Hematological Malignancies

Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University (Other)
Overall Status
Completed
CT.gov ID
NCT01315132
Collaborator
(none)
47
Enrollment
1
Location
1
Arm
136.6
Actual Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This research study uses a drug called cyclophosphamide to decrease the incidence of GVHD in matched sibling hematopoietic stem cell transplant. In doing so, the goal of the study is to increase overall survival.

Condition or DiseaseIntervention/TreatmentPhase
  • Device: Matched Sibling Allogeneic Transplantation
Phase 2

Detailed Description

This research protocol has been developed for patients undergoing matched-sibling hematopoietic stem cell transplant (HSCT). The patients who are treated according to this 2 step allogeneic HSCT protocol will receive cyclophosphamide to induce in-vivo tolerization of both autologous and allogeneic lymphocytes, followed by an allogeneic CD34-selected HSCT. The primary research questions relate to immune reconstitution, incidence of GVHD, and relapse in patients who receive lymphocyte treatment of this type in allogeneic HSCT and how it impacts overall survival.

Study Design

Study Type:
Interventional
Actual Enrollment :
47 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Two Step Approach To Matched-Sibling Allogeneic Hematopoietic Stem Cell Transplantation for High-Risk Hematological Malignancies
Actual Study Start Date :
Apr 10, 2008
Actual Primary Completion Date :
Sep 19, 2018
Actual Study Completion Date :
Aug 29, 2019

Arms and Interventions

ArmIntervention/Treatment
Experimental: Allogeneic Transplantation

Matched Sibling Allogeneic Transplantation

Device: Matched Sibling Allogeneic Transplantation
Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization
Other Names:
  • CliniMACS
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Patients With Overall Survival [1 Year after transplant]

      The primary objective of this prospective, phase II trial was to obtain an OS rate of >60% at 1 year in patients undergoing a 2 step HSCT from an HLA compatible family donor. The >60% threshold was selected as a composite efficacy measure as patients with any hematologic diagnosis, stage of disease, or age as old as 65 years were eligible for this treatment protocol.

    Secondary Outcome Measures

    1. Graft Versus Host Disease (GVHD) [1 Year after transplant]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied.
    Patients will be considered high-risk if they have any of the following:
    1. Age > 50 years

    2. ECOG Performance status of <2

    3. Acute leukemia: requiring more than one chemotherapy regimen to obtain 1st CR; second or greater CR, 1st relapse; any ph+ ALL

    4. CML 2nd chronic phase, accelerated phase, or blastic phase

    5. MDS with IPS of Intermediate 2 or greater

    6. Any myeloproliferative disorder

    7. Hodgkin lymphoma: relapsed, refractory, or primary induction failure

    8. Non-Hodgkin lymphoma: relapsed, refractory, primary treatment failure, or not eligible for an autologous HSCT

    9. Other conditions not listed will be assessed as high-risk by the PI

    10. Patients must have a related donor who is either HLA-identical or a one antigen mismatch at the HLA- A; B; C; and DR loci.

    11. Patients must adequate organ function:

    12. LVEF of >45%

    13. DLCO (adjusted for hemoglobin) >45% of predicted

    14. Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal

    15. Creatinine clearance of > 60 ml/min

    16. Patients must be willing to use contraception if they have childbearing potential

    17. Able to give informed consent

    Exclusion Criteria:
    1. ECOG performance status of 3 or 4.

    2. HIV positive

    3. Active involvement of the central nervous system with malignancy

    4. Psychiatric disorder that would preclude patients from signing an informed consent

    5. Pregnancy

    6. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Thomas Jefferson UniversityPhiladelphiaPennsylvaniaUnited States19107

    Sponsors and Collaborators

    • Sidney Kimmel Cancer Center at Thomas Jefferson University

    Investigators

    • Principal Investigator: Neal Flomenberg, MD, Thomas Jefferson University

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Sidney Kimmel Cancer Center at Thomas Jefferson University
    ClinicalTrials.gov Identifier:
    NCT01315132
    Other Study ID Numbers:
    • 08D.85
    • 2007-61
    First Posted:
    Mar 15, 2011
    Last Update Posted:
    Oct 15, 2019
    Last Verified:
    Sep 1, 2019

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionMatched Sibling Allogeneic Transplantation Matched Sibling Allogeneic Transplantation: Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization
    Period Title: Overall Study
    STARTED47
    COMPLETED46
    NOT COMPLETED1

    Baseline Characteristics

    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionMatched Sibling Allogeneic Transplantation Matched Sibling Allogeneic Transplantation: Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization
    Overall Participants46
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    11
    23.9%
    >=65 years
    35
    76.1%
    Sex: Female, Male (Count of Participants)
    Female
    16
    34.8%
    Male
    30
    65.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    4
    8.7%
    Not Hispanic or Latino
    40
    87%
    Unknown or Not Reported
    2
    4.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    3
    6.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    4
    8.7%
    White
    37
    80.4%
    More than one race
    0
    0%
    Unknown or Not Reported
    2
    4.3%
    Region of Enrollment (participants) [Number]
    United States
    46
    100%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Patients With Overall Survival
    DescriptionThe primary objective of this prospective, phase II trial was to obtain an OS rate of >60% at 1 year in patients undergoing a 2 step HSCT from an HLA compatible family donor. The >60% threshold was selected as a composite efficacy measure as patients with any hematologic diagnosis, stage of disease, or age as old as 65 years were eligible for this treatment protocol.
    Time Frame1 Year after transplant

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionMatched Sibling Allogeneic Transplantation Matched Sibling Allogeneic Transplantation: Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization
    Measure Participants46
    Count of Participants [Participants]
    41
    89.1%
    2. Secondary Outcome
    TitleGraft Versus Host Disease (GVHD)
    Description
    Time Frame1 Year after transplant

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionMatched Sibling Allogeneic Transplantation Matched Sibling Allogeneic Transplantation: Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization
    Measure Participants46
    Acute GVHD
    6
    13%
    Chronic GVHD
    4
    8.7%
    No GVHD
    36
    78.3%

    Adverse Events

    Time Framefrom baseline through one year after transplant
    Adverse Event Reporting Description
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionMatched Sibling Allogeneic Transplantation Matched Sibling Allogeneic Transplantation: Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization
    All Cause Mortality
    Allogeneic Transplantation
    Affected / at Risk (%)# Events
    Total16/46 (34.8%)
    Serious Adverse Events
    Allogeneic Transplantation
    Affected / at Risk (%)# Events
    Total0/46 (0%)
    Other (Not Including Serious) Adverse Events
    Allogeneic Transplantation
    Affected / at Risk (%)# Events
    Total32/46 (69.6%)
    Gastrointestinal disorders
    Mucositis32/46 (69.6%) 32
    Diarrhea30/46 (65.2%) 35

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleNeal Flomenberg, MD
    OrganizationSidney Kimmel Cancer Center at Thomas Jefferson University
    Phone215-955-4367
    EmailNeal.Flomenberg@jefferson.edu
    Responsible Party:
    Sidney Kimmel Cancer Center at Thomas Jefferson University
    ClinicalTrials.gov Identifier:
    NCT01315132
    Other Study ID Numbers:
    • 08D.85
    • 2007-61
    First Posted:
    Mar 15, 2011
    Last Update Posted:
    Oct 15, 2019
    Last Verified:
    Sep 1, 2019