Stem Cell Transplant for Immunologic or Histiocytic Disorders

Hemophagocytic Lymphohistiocytosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00176865
• Other study ID #: MT2002-12
• Secondary ID: 0207M29448
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: December 3, 2017
• Start date: August 2002
• Est. completion date: August 2014

Study information

• Verified date: December 2017
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: August 2014
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Chediak-Higashi Syndrome
• Disease
• Griscelli Syndrome
• Hemophagocytic Lymphohistiocytosis
• Histiocytosis
• Histiocytosis, Langerhans-Cell
• Immunologic Deficiency Syndromes
• Langerhans-Cell Histiocytosis
• Lymphohistiocytosis, Hemophagocytic
• Lymphoproliferative Disorders
• Syndrome
• X-Linked Lymphoproliferative Disorders

Intervention

Procedure:
• Stem Cell Transplant
IV on Day 0

Drug:
• Fludarabine
30mg/m^2 IV Day -7 through Day -3
• Melphalan
140 mg/m^2 IV Day -1
• Anti-thymocyte globulin (ATG)
30 mg/kg IV Day -5 through Day -1
• Campath 1H
0.2 mg/kg IV X 5 days (used as an alternative to Anti-thymocyte globulin (ATG) if unable to tolerate ATG) Day -10 through Day -6
• Cyclosporin A
2.5 mg/kg IV every 12 hours (adults) or every 8 hours (children <40 kg) maintaining a level of >200mg/L Day -3 until Day +180 when, if no GVHD, the dose will be tapered 10% per week beginning on day 181
• Mycophenolate mofetil
15 mg/kg IV or orally bid and discontinued on Day +45 unless GVHD is present
• Intravenous immunoglobulin (IVIG)
500 mg/kg IV weekly beginning on Day +7 until Day +100

Locations

Country	Name	City	State
United States	Masonic Cancer Center University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Mixed Chimerism	>10% Donor Cells at Day 100	Day 100
Secondary	Percentage of Donor Chimerism at 100 Days	The percent of recipient bone marrow and blood cells that are of donor origin.	Day 100
Secondary	Percentage of Donor Chimerism at 180 Days	The percent of recipient bone marrow and blood cells that are of donor origin.	Day 180
Secondary	Percentage of Donor Chimerism at 365 Days	The percent of recipient bone marrow and blood cells that are of donor origin.	Day 365
Secondary	Incidence of Grade 2-4 Acute Graft Versus Host Disease (aGVHD)	Acute graft versus host disease (aGVHD) is a reaction occurring within the first 100 days after transplant where the T- cells of the donor graft attacks the recipient's (host's) skin, GI tract, liver and other organs. The severity of aGVHD is graded on a scale of 1 - 4 with the highest number representing the most severe disease.	Day 100
Secondary	Incidence of Grade 3-4 Acute Graft Versus Host Disease (aGVHD)	Acute graft versus host disease (aGVHD) is a reaction occurring within the first 100 days after transplant where the T- cells of the donor graft attacks the recipient's (host's) skin, GI tract, liver and other organs. The severity of aGVHD is graded on a scale of 1 - 4 with the highest number representing the most severe disease.	Day 100
Secondary	Incidence of Chronic Graft Versus Host Disease (cGVHD)	Chronic graft versus host disease (cGVHD) is a reaction which typically develops 3 to 6 months after transplant where the T- cells of the donor graft attacks the recipient's (host's) skin, GI tract, liver and other organs.	6 months and 1 year
Secondary	Number of Subjects Alive at 100 Days		Day 100
Secondary	Number of Subjects Alive at One Year		Day 365
Secondary	Compare Quality of Life (QOL)		Pretransplant, 1 year, 2 years and 5 years