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

April 6, 2022 updated by: Joel Brochstein, Northwell Health

A Two Step Approach to Allogeneic Hematopoietic Stem Cell Transplantation From HLA Partially-Matched Related Donors for Patients With Hematologic Malignancies

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

10

Phase

  • Phase 3

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
    • New York
      • New Hyde Park, New York, United States, 11040
        • Cohen Children's Medical Center

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

Ages Eligible for Study

2 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hematopoietic engraftment
Time Frame: Day +30 post-transplantation
Absolute neutrophil count >500/microliter x 3 consecutive days
Day +30 post-transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-Year disease-free survival
Time Frame: 2 years post-transplantation
Alive and free of disease at 2 years post-transplantation
2 years post-transplantation
Grade II-IV GvHD
Time Frame: Day +100 post-transplantatation
Proportion of subjects with Grade II-IV acute graft-versus-host disease
Day +100 post-transplantatation
Grade III-IV GvHD
Time Frame: Day +100 post-transplantation
Proportion of subjects with Grade III-IV acute graft-versus-host disease
Day +100 post-transplantation
Relapse rate
Time Frame: 2 years post-transplantation
Proportion of subjects who have experienced disease relapse by 2 years post-transplantation
2 years post-transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwell Health

Collaborators

New York Blood Center

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

December 1, 2014

Primary Completion (Actual)

January 14, 2022

Study Completion (Actual)

February 14, 2022

Study Registration Dates

First Submitted

September 30, 2015

First Submitted That Met QC Criteria

September 30, 2015

First Posted (Estimate)

October 2, 2015

Study Record Updates

Last Update Posted (Actual)

April 7, 2022

Last Update Submitted That Met QC Criteria

April 6, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-551

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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