Stem Cell Transplantation From HLA Partially-Matched Related Donors for Patients With Hematologic Malignancies

Sponsor
Northwell Health (Other)
Overall Status
Completed
CT.gov ID
NCT02566395
Collaborator
New York Blood Center (Other)
10
Enrollment
1
Location
1
Arm
86.5
Duration (Months)
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This clinical pilot trial is intended to evaluate the feasibility, efficacy and safety of hematopoietic stem cell transplantation (HSCT) from Human Leukocyte Antigen (HLA)-mismatched related donors for children and young adults with hematologic malignancies who lack a suitably matched related or unrelated donor. The methodology will be one that has been successfully utilized in adult patients at Thomas Jefferson University.

Condition or DiseaseIntervention/TreatmentPhase
  • Radiation: Radiation
  • Drug: Cyclophosphamide
  • Biological: Donor Lymphocyte Infusion (DLI)
  • Biological: Haploidentical Stem Cell Transplantation
Phase 3

Detailed Description

Allogeneic HSCT is a potentially curative therapy for a number of malignancies. A barrier to the institution of this potentially curative strategy in hematologic malignancies is the availability of donors. Only 30% of patients in North America or Europe who may benefit from allogeneic HSCT will have an available HLA matched sibling donor. The ability to find a matched sibling donor is proportional to the number of children in the family. Because of the decreasing size of nuclear families, it is becoming less likely for patients to have an HLA identical matched sibling. Registries can provide a matched unrelated allogeneic stem cell graft for an additional 30% of patients. However this is not an option for patients who do not have a match in the registry, or whose disease status precludes them from waiting to identify an appropriate unrelated donor. The ability of finding a well matched unrelated donor is even more limited for segments of the population with mixed race ancestry as well as for African Americans who, because of a higher degree of HLA diversity, will be unlikely to find an unrelated donor who matches their HLA type.

In these settings it is easier and faster to identify a partially HLA-matched (or haploidentical) family member as a stem cell donor. The use of haploidentical donors broadens the application of HSCT because it is not as limited by family size or racial/ethnic HLA diversity. Because parents and children, as well as siblings can be used as haploidentical donors, this type of transplant enfranchises almost every segment of the population.

Since, in this study, the donor lymphoid and stem cell portions of the graft are collected and administered at different time points during the conditioning regimen, this approach to haploidentical HSCT is referred to as a 2 Step regimen. The approach does not involve ex vivo T cell depletion, but uses cyclophosphamide to tolerize donor lymphocytes within the framework of a myeloablative conditioning regimen. Preliminary experience with this approach in adult patients at Thomas Jefferson University for myeloablative haploidentical HSCT dates back to 2005 with the first trial using myeloablative conditioning formally launched in 2006. That initial trial met its accrual goals and the current trial is one of the successor trials derived from that experience.

The conditioning regimen includes total body irradiation (TBI) (1.5 Gray x 8) and CY (60 mg/kg x 2). Tacrolimus and Mycophenolate Mofetil (MMF) are used as post-transplant immunosuppression in relatively standard fashion.

The novel aspect of the regimen is in the administration of the graft. If one considers that a standard allograft consists of two components, a lymphoid portion and a stem cell portion, what is unique here is the administration of these two portions separately, at different time points during the conditioning regimen rather than together. The lymphoid portion, including a fixed dose of CD3+ cells/kg is administered prior to cyclophosphamide while the hematopoietic stem cell (HSC) portion of the graft is administered after cyclophosphamide has been metabolized and eliminated. Thus, the transplant occurs in 2 steps.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
10 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation From HLA Partially-Matched Related Donors for Patients With Hematologic Malignancies
Study Start Date :
Dec 1, 2014
Actual Primary Completion Date :
Jan 14, 2022
Actual Study Completion Date :
Feb 14, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Haploidentical Stem Cell Transplantation

Subjects will receive pretransplantation conditioning of total-body irradiation (1,200 cGy delivered in 8 fractions over 4 days [Days -9 through -6] and cyclophosphamide (60 mg/kg IV daily x 2 on Days -3 and -2). Donor lymphocyte infusion will occur on day -6; donor CD34+ cells will be infused on Day 0.

Radiation: Radiation
1,200 cGy, delivered in 8 fractions of 150 cGy bid x 4 days
Other Names:
  • Total Body Irradiation
  • Drug: Cyclophosphamide
    Cyclophosphamide 60 mg/kg IV daily x 2 consecutive days
    Other Names:
  • Cytoxan
  • Biological: Donor Lymphocyte Infusion (DLI)
    DLI containing 1 x 10E8/kg donor T-cells

    Biological: Haploidentical Stem Cell Transplantation
    2-10 x 10E6/kg donor CD34+ selected cells

    Outcome Measures

    Primary Outcome Measures

    1. Hematopoietic engraftment [Day +30 post-transplantation]

      Absolute neutrophil count >500/microliter x 3 consecutive days

    Secondary Outcome Measures

    1. 2-Year disease-free survival [2 years post-transplantation]

      Alive and free of disease at 2 years post-transplantation

    2. Grade II-IV GvHD [Day +100 post-transplantatation]

      Proportion of subjects with Grade II-IV acute graft-versus-host disease

    3. Grade III-IV GvHD [Day +100 post-transplantation]

      Proportion of subjects with Grade III-IV acute graft-versus-host disease

    4. Relapse rate [2 years post-transplantation]

      Proportion of subjects who have experienced disease relapse by 2 years post-transplantation

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 21 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Acute lymphoblastic leukemia

    • Acue myelogenous leukemia

    • Myelodysplastic syndrome

    • Non-Hodgkin lymphoma

    • Chronic myelogenous leukemia

    • Adequate lung, liver, renal, cardiac function

    • Performance status >70

    • Available related donor who is mismatched at ≥ 2 HLA alleles

    Exclusion Criteria:
    • Available HLA-identical related donor

    • HIV positive

    • Active uncontrolled infection

    • Pregnancy

    • Performance status ≤70

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Cohen Children's Medical CenterNew Hyde ParkNew YorkUnited States11040

    Sponsors and Collaborators

    • Northwell Health
    • New York Blood Center

    Investigators

    • Principal Investigator: Joel A Brochstein, MD, Cohen Children's Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Joel Brochstein, Associate Chief for Cellular Therapy, CCMC, Northwell Health
    ClinicalTrials.gov Identifier:
    NCT02566395
    Other Study ID Numbers:
    • 14-551
    First Posted:
    Oct 2, 2015
    Last Update Posted:
    Apr 7, 2022
    Last Verified:
    Apr 1, 2022

    Study Results

    No Results Posted as of Apr 7, 2022