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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT00429143
First received: January 29, 2007
Last updated: May 30, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Hematologic Malignancies
Radiation: Total Body Irradiation (TBI)
Biological: Donor Lymphocyte Infusion (DLI)
Drug: Cyclophosphamide (CY)
Drug: Tacrolimus
Drug: Mycophenolate Mofetil (MMF)
Biological: Hematopoietic Stem Cell Transplant (HSCT)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Two Step Approach To Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies From HLA Partially-Matched Related Donors

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Overall Survival of Participants [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine overall survival at 6 months post-transplant.

  • Optimal Dose of CD3+ Donor Lymphocytes (T-cells) for Consistent Engraftment Without GVHD [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

    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 Outcome Measures:
  • Engraftment Rates [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    To assess hematopoietic engraftment rates.

  • Lymphoid Recovery [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To assess the pace of lymphoid recovery in this patient population.

  • Incidence of Grades III-IV GVHD [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

    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)



Enrollment: 27
Study Start Date: January 2006
Study Completion Date: June 2010
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Haploidentical Allogeneic Transplantation
Patients undergoing hematopoietic stem cell transplant from a partially matched related donor
Radiation: Total Body Irradiation (TBI)
TBI twice daily days 6-9 prior to transplant (HSCT)
Other Names:
  • TBI
  • radiotherapy
Biological: Donor Lymphocyte Infusion (DLI)
DLI given 6 days prior to transplant (HSCT).
Other Names:
  • DLI
  • T cell infusion
Drug: Cyclophosphamide (CY)
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
Drug: Tacrolimus
Tacrolimus given one day prior to transplant (HSCT).
Other Names:
  • FK-506
  • fujimycin
  • Prograf
  • Advagraf
  • Protopic
Drug: Mycophenolate Mofetil (MMF)
MMF given one day prior to transplant (HSCT).
Other Names:
  • MMF
  • CellCept
  • Myfortic
Biological: Hematopoietic Stem Cell Transplant (HSCT)
CD34+ selected Hematopoietic Stem Cell Transplant (HSCT) is performed. This is the day of transplantation.
Other Names:
  • HSCT
  • stem cell transplant

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  2. 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.
  3. Patients without a well-matched unrelated donor or those who have a disease status that precludes a wait for an identified unrelated donor.
  4. 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
  5. Performance status > 60% (Karnofsky)
  6. Patients must be willing to use contraception if they have childbearing potential
  7. Able to give informed consent

Exclusion Criteria:

  1. An eligible HLA-identical sibling donor.
  2. Performance status < 60% (Karnosfsky)
  3. HIV positive
  4. Active involvement of the central nervous system with malignancy
  5. Psychiatric disorder that would preclude patients from signing an informed consent
  6. Pregnancy
  7. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00429143

Locations
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Thomas Jefferson University
Investigators
Principal Investigator: Neal Flomenberg, MD Thomas Jefferson University
  More Information

Additional Information:
No publications provided by Thomas Jefferson University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT00429143     History of Changes
Other Study ID Numbers: 06U.20, 2005-84
Study First Received: January 29, 2007
Results First Received: June 4, 2012
Last Updated: May 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Thomas Jefferson University:
Hematologic Malignancies
Two Step Approach
Haploidentical Transplant

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Cyclophosphamide
Mycophenolate mofetil
Tacrolimus
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014