Overview

This trial is active, not recruiting.

Conditions hemophagocytic lymphohistiocytosis, x-linked lymphoproliferative disorders, chediak-higashi syndrome, griscelli syndrome, immunologic deficiency syndromes, langerhans-cell histiocytosis
Treatments stem cell transplant, fludarabine, melphalan, atg or campath
Phase phase 2
Sponsor Masonic Cancer Center, University of Minnesota
Start date August 2002
End date August 2012
Trial size 30 participants
Trial identifier NCT00176865, 0207M29448, MT2002-12

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
human leukocyte antigen (HLA) genotypic matched sibling donor
stem cell transplant hematopoietic stem cell transplant
Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells
fludarabine, melphalan, atg or campath Fludara; Atgam; Campath-1H, Alkeran
all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day
(Active Comparator)
HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor,
stem cell transplant hematopoietic stem cell transplant
Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells
fludarabine, melphalan, atg or campath Fludara; Atgam; Campath-1H, Alkeran
all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day
(Active Comparator)
two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord).
stem cell transplant hematopoietic stem cell transplant
Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells
fludarabine, melphalan, atg or campath Fludara; Atgam; Campath-1H, Alkeran
all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day

Primary Outcomes

Measure
To demonstrate the safety and the ability to establish stable mixed chimerism (>10% donor cells at day 100) using a nonmyeloablative preparative regimen in a phase 2 pilot trial
time frame: Day 100

Secondary Outcomes

Measure
Determine the incidence of chimerism at 100 days, 6 months and 1 year
time frame: 100 days, 6 months and 1 year
Determine the incidence of grade 2-4 and 3-4 acute graft versus host disease (aGVHD)
time frame: Day 100
Determine the incidence of chronic graft versus host disease (cGVHD)
time frame: 6 months and 1 year
Compare quality of life (QOL)
time frame: Pretransplant, 1 year, 2 years and 5 years
Determine overall survival
time frame: Day 100 and 1 year

Eligibility Criteria

Male or female participants up to 35 years old.

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

Additional Information

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
Principal investigator Angela Smith, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2012.
Information provided to ClinicalTrials.gov by Masonic Cancer Center, University of Minnesota.