Reduced Intensity Transplant Using Extracorporeal Photopheresis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by Ann & Robert H Lurie Children's Hospital of Chicago.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Therakos
Information provided by:
Ann & Robert H Lurie Children's Hospital of Chicago
ClinicalTrials.gov Identifier:
NCT00179790
First received: September 9, 2005
Last updated: March 10, 2011
Last verified: February 2009
  Purpose

Stem cell transplantation may be used to cure childhood cancers, and other diseases. Traditionally, stem cell transplants use high doses of chemotherapy and radiation. This regimen may cause significant problems after transplant such as infertility, infection, and graft versus host disease (GVHD).

Reduced intensity transplant (RIT) uses medications which weaken the immune system, allowing donor cells to take over. The goal of a RIT is to reduce the risk for complications after transplant. Usually medication is used to weaken the immune system, but there are other options such as extracorporeal photopheresis (ECP) that may be less toxic.

ECP is currently used for the treatment of GVHD and certain lymphomas. ECP uses a machine that filters white blood cells from the blood, treats them with ultraviolet (UV) light, and then gives all the cells back to the patient. The patient's immune system becomes weaker, allowing the donor cells to replace those of the patient. Studies involving the use of ECP for conditioning have shown fewer side effects than the use of medications.

The primary purpose of this clinical research trial is to evaluate the safety and feasibility of ECP as part of a preparative regimen for RIT in children and young adults.


Condition Intervention Phase
Leukemia
Cancer
Procedure: Extracorporeal Photopheresis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reduced Intensity Stem Cell Transplant in Children and Young Adults Utilizing Photopheresis, Fludarabine, and Busulfan

Resource links provided by NLM:


Further study details as provided by Ann & Robert H Lurie Children's Hospital of Chicago:

Primary Outcome Measures:
  • To determine the feasibility of using photopheresis as the backbone of a reduced intensity transplant regimen to reduce transplant related mortality and acute and chronic graft versus host disease (GVHD) [ Time Frame: Throughout Treatment ] [ Designated as safety issue: Yes ]
  • To determine time to engraftment and the percentage of patients achieving full engraftment by day +100. Engraftment will be defined as > 95% total donor chimerism as determined by restriction fragment length polymorphism (RFLP). [ Time Frame: By Day +100 ] [ Designated as safety issue: Yes ]
  • To determine the rate of grades III and IV acute GVHD. [ Time Frame: Throughout Treatment ] [ Designated as safety issue: Yes ]
  • To evaluate 100 day transplant related mortality [ Time Frame: Through Day +100 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To establish patterns of biological effects of photopheresis on dendritic cell and CD4/CD8 populations, CD4/CD25 populations, IFN-gamma, TNF-alpha, IL-10, IL-12, and IL-4 [ Time Frame: Pre Transplant through 1 year post stem cell transplant ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: July 2005
Estimated Study Completion Date: January 2010
Estimated Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Extracorporeal Photopheresis
    Patient will undergo ECP treatment pre and post stem cell transplant infusion
Detailed Description:

This study tests the feasibility of a reduced intensity preparative regimen for stem cell transplant including extracorporeal photopheresis (ECP), busulfan, and fludarabine in patients with leukemia, lymphoma, and certain non-malignant diseases. The current reduced intensity protocol includes busulfan, fludarabine, and anti-thymocyte immunoglobulin. ECP is currently used in diseases such as chronic GVHD and cutaneous T cell lymphoma. The mechanism of ECP has not been defined. It is hypothesized that exposure of white blood cells to ultraviolet light with 8-methoxypsoralen initiates an apoptotic cellular cascade. Apoptotic cells are recognized and removed by the reticuloendothelial system, initiating the secretion of anti-inflammatory cytokines and the reduction of proinflammatory cytokines. Antigen presenting cells then regulate immune responses through the induction of tolerance.

Here we incorporate the use of ECP, fludarabine, and busulfan in the preparative regimen, followed by ECP as prophylaxis for acute graft versus host disease. We hypothesize that photopheresis is safe and feasible, and patients will have similar rates of engraftment with less GVHD as those treated with current reduced intensity protocols. The use of ECP prior to transplant provides immunosuppression promoting host engraftment. Furthermore, the introduction of ECP following transplant may be able to induce tolerance thereby reducing rates of GVHD.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Weight > 25 kg
  • Patients with acute lymphoblastic leukemia (ALL) who are in CR (complete remission; < 5% blasts in bone marrow and no active central nervous system disease) who:

    • Are in second remission with an initial remission of < 36 months.
    • Patients with "high risk" disease in CR1, defined by karyotype abnormalities such as presence of (9;22) translocation, monosomy 7, or monosomy 5; and/or patients with slow initial response (initial remission not reached within four weeks from diagnosis).
    • Are in third (or subsequent) remission
    • Experience isolated extramedullary relapse while on therapy
    • Have experienced relapse following myeloablative stem cell transplant
    • Are WT1+ following induction therapy
  • Patients with acute myelogenous leukemia (AML) who:

    • Are in first remission and remain WT1 positive.
    • Are in second remission
    • Are in initial partial remission (< 20% blasts in bone marrow)
    • Experience relapse following myeloablative stem cell transplant
  • Patients with relapsed lymphoma whose residual disease appears to be chemo-responsive and non-bulky (< 5 cm largest diameter)
  • Patients with chronic myelogenous leukemia (CML) in chronic phase who:

    • Don't achieve remission (molecular or cytogenetic) by 1 year of diagnosis with therapy (imatinib mesylate or interferon)
    • Have a rising quantitative bcr/abl on imatinib mesylate (molecular relapse)
    • Had developed accelerated phase regardless of therapy but are now back in second chronic phase
  • Patients with recurrent solid tumors (neuroblastoma, Ewing's sarcoma, melanoma, rhabdomyosarcoma)
  • Patients with myelodysplastic syndrome
  • Patients with refractory anemia (RA) and refractory anemia with excess blasts (RAEB) are eligible, but refractory anemia with excess blasts in transformation (RAEB-T) patients are only eligible if treated to < 20% blasts with chemotherapy
  • Patients with selected immunodeficiencies such as Wiskott-Aldrich syndrome or hyper-IgM syndrome
  • Patients with metabolic diseases such as Niemann-Pick or adrenoleukodystrophy
  • Patients with bone marrow failure syndromes, including aplastic anemia
  • Adequate venous access
  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: NCT00179790

Contacts
Contact: Jennifer Schneiderman, MD, MS 773-880-4562 jschneiderman@childrensmemorial.org
Contact: Colleen Schaefer, BS 773-880-3459 cschaefer@childrensmemorial.org

Locations
United States, Illinois
Children's Memorial Hospital Recruiting
Chicago, Illinois, United States, 60614
Contact: Jennifer Schneiderman, MD, MS    773-880-4562    jschneiderman@childrensmemorial.org   
Contact: Colleen Schaefer, BS    773-880-3459    cschaefer@childrensmemorial.org   
Sponsors and Collaborators
Ann & Robert H Lurie Children's Hospital of Chicago
Therakos
Investigators
Principal Investigator: Jennifer Schneiderman, MD, MS Ann & Robert H Lurie Children's Hospital of Chicago
  More Information

No publications provided

Responsible Party: Jennifer Schneiderman, MD, Children's Memorial Hospital
ClinicalTrials.gov Identifier: NCT00179790     History of Changes
Other Study ID Numbers: ECP RIT
Study First Received: September 9, 2005
Last Updated: March 10, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Ann & Robert H Lurie Children's Hospital of Chicago:
cancer
hemoglobinopathy
immune deficiency
photopheresis
ECP
extracorporeal photopheresis

Additional relevant MeSH terms:
Leukemia
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on July 24, 2014