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Completed

NCT Number: NCT00429143

A Two-Step Approach to Bone Marrow Transplant Using Cells From A Partially-Matched Relative

The purpose of this study is to develop a way of treating patients who do not have a completely matched family donor or a readily available unrelated donor with bone marrow transplant by using a partially-matched family donor. Patients receiving this type of transplant will receive chemotherapy and/or radiation to treat their disease. They will also receive their donor's cells in 2 parts. During the first part, the donor's lymphocytes will be exposed to one of the chemotherapy agents to help the patient become tolerant to the lymphocytes. In the second part of the transplant, the patient will receive their donor's stem cells to help recover their peripheral blood counts and establish long-term engraftment. The hypothesis of this study is that in partially-matched allogeneic transplant, there is a defined number of donor T-cells that can be treated and given to the recipient to avoid post-transplant infection without causing severe graft-versus-host disease.

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Key information

Conditions

Hematologic Malignancies Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Neoplasms Neoplasms by Site

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

About this study

Haploidentical hematopoietic stem cell transplant is a life-saving therapy for patients who are without well matched donors. This type of therapy has been associated with poor outcomes in the past due to complications such as infection. The Jefferson 2 Step approach was designed to allow the infusion of an exact dose of tolerized lymphocytes in haploidentical transplant in order to allow for immune reconstitution post transplant to avoid infectious complications while still having acceptable rates of GVHD. In this approach, patients with high-risk hematological malignancies undergo 8 fractions of TBI (12 Gy) followed by an exact dose of donor lymphocytes. The phase I portion of the study determined the optimal dose of lymphocytes. Two days after receiving the donor lymphocytes, the patients receive 2 daily doses of cyclophosphamide. One day after receiving cyclophosphamide, the patients receive stem cell from their donor. Tacrolimus and mycophenylate mofetil are used as GVHD prophylaxis.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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 must have a related donor who is either a one, two or three out of six antigen mismatch at the HLA-A;B;DR loci.
  • Patients without a well-matched unrelated donor or those who have a disease status that precludes a wait for an identified unrelated donor.
  • Patients must adequate organ function:
  • LVEF of >45%
  • FVC or FEV1 >45% of predicted
  • Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal
  • Serum creatinine < 2.0 mg/dl or creatinine clearance of > 40 ml/min
  • Performance status > 60% (Karnofsky)
  • Patients must be willing to use contraception if they have childbearing potential
  • Able to give informed consent

Exclusion criteria

  • An eligible HLA-identical sibling donor.
  • Performance status < 60% (Karnosfsky)
  • HIV positive
  • Active involvement of the central nervous system with malignancy
  • Psychiatric disorder that would preclude patients from signing an informed consent
  • Pregnancy
  • Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder.

Treatment and study plan

Total body irradiation (TBI)

Radiation

TBI twice daily days 6-9 prior to transplant (HSCT)

Other names: TBI, radiotherapy

Donor Lymphocyte Infusion (DLI)

Biological

DLI given 6 days prior to transplant (HSCT).

Other names: DLI, T cell infusion

Cyclophosphamide (CY)

Drug

Cyclophosphamide given once daily at 60 mg/kg on days 2 and 3 prior to transplant (HSCT).

Other names: CY, Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane

Tacrolimus

Drug

Tacrolimus given one day prior to transplant (HSCT).

Other names: FK-506, fujimycin, Prograf, Advagraf, Protopic

Mycophenolate Mofetil (MMF)

Drug

MMF given one day prior to transplant (HSCT).

Other names: MMF, CellCept, Myfortic

Hematopoietic Stem Cell Transplant (HSCT)

Biological

CD34+ selected Hematopoietic Stem Cell Transplant (HSCT) is performed. This is the day of transplantation.

Other names: HSCT, stem cell transplant

Primary outcomes

  1. Overall Survival of Participants

    Time frame: 6 months

    To determine overall survival at 6 months post-transplant.

  2. Optimal Dose of CD3+ Donor Lymphocytes (T-cells) for Consistent Engraftment Without GVHD

    Time frame: 6 months

    To determine the optimal dose of CD3+ donor lymphocytes required for consistent engraftment without the development of grade III/IV GVHD.

    Measured as CD3+ donor lymphocytes given as n x 10^8/kg.

    "n" was found to be 2 and was found to be the optimal dose and was the only dose given.

Secondary outcomes

  1. Engraftment Rates

    Time frame: 6 months

    To assess hematopoietic engraftment rates.

  2. Lymphoid Recovery

    Time frame: 6 months

    To assess the pace of lymphoid recovery in this patient population.

  3. Incidence of Grades III-IV GVHD

    Time frame: 6 months

    To determine the incidence and severity of GVHD in these patients using a combination of cyclophosphamide, tacrolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis.'

    Severity was graded using CTCAE 3.0 (1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death)

Sponsors and collaborators

Lead sponsor

Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Other

Registry information

Official study title

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

Important dates

Study start
2006
Primary completion
2009
Study completion
2010
First posted
Jan 31, 2007
Registry last updated
May 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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