Clinical trial NCT00176865: Stem Cell Transplant for Immunologic or Histiocytic Disorders
Official title: Allogeneic Hematopoietic Stem Cell Transplant for Patients With Immunologic or Histiocytic Disorders Using a Non-Myeloablative Preparative Regimen to Achieve Stable Mixed Chimerism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemophagocytic Lymphohistiocytosis
X-Linked Lymphoproliferative Disorders
Chediak-Higashi Syndrome
Griscelli Syndrome
Immunologic Deficiency Syndromes
Langerhans-Cell Histiocytosis
Keywords: Stem cell transplant
immunodeficiency
donor lymphocyte infusion
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2005-09-15
Enrollment: 19
Sex: ALL
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study tests the clinical outcomes of a preparative regimen of fludarabine (FLU), anti-thymocyte globulin (ATG)/or Campath, and melphalan; followed by hematopoietic stem cell transplant, and a post transplant regimen of Cyclosporin A (CsA) in patients with immunologic or histiocytic disorders. The researchers hypothesize that this regimen will have a positive effect on post transplant engraftment and the incidence of graft-versus-host-disease (GVHD).

Patients will be randomized biologically into one of 3 arms based upon donor availability: (a) human leukocyte antigen (HLA) genotypic matched sibling donor, (b) HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor, (c) two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord).

Detailed description: Prior to transplantation, subjects will receive Melphalan, Fludarabine and Anti-Thymocyte Globulin (ATG) or Campath. These three drugs are being given to subjects to help the new stem cells take and grow. On the day of transplantation, subjects will receive stem cells transfused via intravenous (IV) catheter.

After stem cell transplantation, subjects will be given Cyclosporin A (CsA) and mycophenolate mofetil (MMF) to reduce the risk of graft-versus-host disease, the complication that occurs when the donor's stem cells react against the patient.

Eligibility criteria: Inclusion Criteria:

Patients with immunodeficiencies or histiocytic disorders 0-35 years of age with an acceptable stem cell donor and disease characteristic defined by the following:

* Patients with histocytic disorders (hemophagocytic lymphohistiocytosis of any etiology and refractory Langerhans cell histiocytosis) who do not meet eligibility criteria for a myeloablative transplant procedure
* Patients with immunodeficiency disorders in whom residual immune function may not require a fully myeloablative preparative regimen or patient is ineligible for standard myeloablative preparative regimen (any form of severe combined immunodeficiency \[SCID\], or other immunodeficiency with T cell defect)
* Patients with immunodeficiency disorders that have had poor outcome with myeloablative stem cell transplants (including, but not limited to, common variable immunodeficiency \[CVID\], Wiskott Aldrich Syndrome \[WAS\] if \> 5 years of age, ataxia telangiectasia)
* Patients with immunodeficiencies or histocytic disorders that require a second stem cell transplant (SCT) for any reason

Exclusion Criteria:

* Karnofsky or Lansky performance score \<70
* Glomerular filtration rate (GFR)\<30% predicted
* Cardiac function \<50% normal by echocardiogram
* Serum creatinine \> 2x normal for age/weight
* Pregnant or lactating females
* Active serious infection that has not had an adequate course of therapy pre-SCT. Any patient with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) or human immunodeficiency virus (HIV) seropositivity

Primary outcomes:
measure: Number of Subjects With Mixed Chimerism
timeFrame: Day 100
Secondary outcomes:
measure: Percentage of Donor Chimerism at 100 Days
timeFrame: Day 100
measure: Percentage of Donor Chimerism at 180 Days
timeFrame: Day 180
measure: Percentage of Donor Chimerism at 365 Days
timeFrame: Day 365
measure: Incidence of Grade 2-4 Acute Graft Versus Host Disease (aGVHD)
timeFrame: Day 100
measure: Incidence of Grade 3-4 Acute Graft Versus Host Disease (aGVHD)
timeFrame: Day 100
measure: Incidence of Chronic Graft Versus Host Disease (cGVHD)
timeFrame: 6 months and 1 year
measure: Number of Subjects Alive at 100 Days
timeFrame: Day 100
measure: Number of Subjects Alive at One Year
timeFrame: Day 365
measure: Compare Quality of Life (QOL)
timeFrame: Pretransplant, 1 year, 2 years and 5 years
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Angela Smith, MD
role: PRINCIPAL_INVESTIGATOR
References: