Stem Cell Transplant for Immunologic or Histiocytic Disorders - Full Text View

Purpose

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).

Condition	Intervention	Phase
Hemophagocytic Lymphohistiocytosis X-Linked Lymphoproliferative Disorders Chediak-Higashi Syndrome Griscelli Syndrome Immunologic Deficiency Syndromes Langerhans-Cell Histiocytosis	Procedure: Stem Cell Transplant Drug: Fludarabine, melphalan, ATG or Campath	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: Chediak-Higashi syndrome complement factor I deficiency familial hemophagocytic lymphohistiocytosis Langerhans cell histiocytosis X-linked lymphoproliferative disease

Drug Information available for: Melphalan Melphalan hydrochloride Fludarabine Fludarabine phosphate Alemtuzumab

U.S. FDA Resources

Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Determine the incidence of chimerism at 100 days, 6 months and 1 year [ Time Frame: 100 days, 6 months and 1 year ] [ Designated as safety issue: Yes ]
Determine the incidence of grade 2-4 and 3-4 acute graft versus host disease (aGVHD) [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
Determine the incidence of chronic graft versus host disease (cGVHD) [ Time Frame: 6 months and 1 year ] [ Designated as safety issue: Yes ]
Compare quality of life (QOL) [ Time Frame: Pretransplant, 1 year, 2 years and 5 years ] [ Designated as safety issue: No ]
Determine overall survival [ Time Frame: Day 100 and 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	August 2002
Estimated Study Completion Date:	August 2017
Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm 1 - Matched sibling donor human leukocyte antigen (HLA) genotypic matched sibling donor	Procedure: Stem Cell Transplant Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells Other Name: hematopoietic stem cell transplant Drug: Fludarabine, melphalan, ATG or Campath all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day Other Name: Fludara; Atgam; Campath-1H, Alkeran
Active Comparator: Arm 2 - Matched unrelated donor HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor,	Procedure: Stem Cell Transplant Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells Other Name: hematopoietic stem cell transplant Drug: Fludarabine, melphalan, ATG or Campath all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day Other Name: Fludara; Atgam; Campath-1H, Alkeran
Active Comparator: Arm 3 - Mismatched double cord donors two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord).	Procedure: Stem Cell Transplant Reduced intensity chemotherapy followed by infusion of hematopoietic stem cells Other Name: hematopoietic stem cell transplant Drug: Fludarabine, melphalan, ATG or Campath all drugs are given intravenously (IV). Fludarabine x 5 days and melphalan x 1 day Other Name: Fludara; Atgam; Campath-1H, Alkeran

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

Ages Eligible for Study:	up to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00176865

Locations

United States, Minnesota
Masonic Cancer Center University of Minnesota
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

Principal Investigator:

Angela Smith, MD

Masonic Cancer Center, University of Minnesota

More Information

No publications provided

Responsible Party:	Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:	NCT00176865 History of Changes
Other Study ID Numbers:	MT2002-12, 0207M29448
Study First Received:	September 12, 2005
Last Updated:	October 26, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:

Stem cell transplant
immunodeficiency
donor lymphocyte infusion

Additional relevant MeSH terms:

Chediak-Higashi Syndrome
Histiocytosis
Histiocytosis, Langerhans-Cell
Immunologic Deficiency Syndromes
Lymphohistiocytosis, Hemophagocytic
Lymphoproliferative Disorders
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Immune System Diseases
Lymphatic Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Histiocytosis, Non-Langerhans-Cell

Immunoproliferative Disorders
Melphalan
Fludarabine
Fludarabine monophosphate
Alemtuzumab
Campath 1G
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on May 23, 2013