Stem Cell Transplant for Immunologic or Histiocytic Disorders

NCT00176865 | Completed Phase 2 Results DMC

• 2 other identifiers: MT2002-120207M29448
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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).

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

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Mixed Chimerism

  \>10% Donor Cells at Day 100

  Day 100

Secondary Outcomes (9)

• Percentage of Donor Chimerism at 100 Days

  Day 100

• Percentage of Donor Chimerism at 180 Days

  Day 180

• Percentage of Donor Chimerism at 365 Days

  Day 365

• Incidence of Grade 2-4 Acute Graft Versus Host Disease (aGVHD)

  Day 100

• Incidence of Grade 3-4 Acute Graft Versus Host Disease (aGVHD)

  Day 100

Study Arms (3)

Arm 1 - Matched sibling donor

ACTIVE COMPARATOR

Stem Cell Transplant: human leukocyte antigen (HLA) genotypic matched sibling donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)

Procedure: Stem Cell Transplant; Drug: Fludarabine; Drug: Melphalan; Drug: Anti-thymocyte globulin (ATG); Drug: Campath 1H; Drug: Cyclosporin A; Drug: Mycophenolate mofetil; Drug: Intravenous immunoglobulin (IVIG)

Arm 2 - Matched unrelated donor

ACTIVE COMPARATOR

Stem Cell Transplant: HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)

Procedure: Stem Cell Transplant; Drug: Fludarabine; Drug: Melphalan; Drug: Anti-thymocyte globulin (ATG); Drug: Campath 1H; Drug: Cyclosporin A; Drug: Mycophenolate mofetil; Drug: Intravenous immunoglobulin (IVIG)

Arm 3 - Mismatched double cord donors

ACTIVE COMPARATOR

Stem Cell Transplant: two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord) and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)

Procedure: Stem Cell Transplant; Drug: Fludarabine; Drug: Melphalan; Drug: Anti-thymocyte globulin (ATG); Drug: Campath 1H; Drug: Cyclosporin A; Drug: Mycophenolate mofetil; Drug: Intravenous immunoglobulin (IVIG)

Interventions

Stem Cell Transplant PROCEDURE

IV on Day 0

Also known as: hematopoietic stem cell transplant

Arm 1 - Matched sibling donor; Arm 2 - Matched unrelated donor; Arm 3 - Mismatched double cord donors

Fludarabine DRUG

30mg/m\^2 IV Day -7 through Day -3

Also known as: Fludara

Arm 1 - Matched sibling donor; Arm 2 - Matched unrelated donor; Arm 3 - Mismatched double cord donors

Melphalan DRUG

140 mg/m\^2 IV Day -1

Also known as: Alkeran

Arm 1 - Matched sibling donor; Arm 2 - Matched unrelated donor; Arm 3 - Mismatched double cord donors

Anti-thymocyte globulin (ATG) DRUG

30 mg/kg IV Day -5 through Day -1

Also known as: ATGAM

Arm 1 - Matched sibling donor; Arm 2 - Matched unrelated donor; Arm 3 - Mismatched double cord donors

Campath 1H DRUG

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

Also known as: Alemtuzumab

Arm 1 - Matched sibling donor; Arm 2 - Matched unrelated donor; Arm 3 - Mismatched double cord donors

Cyclosporin A DRUG

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

Arm 1 - Matched sibling donor; Arm 2 - Matched unrelated donor; Arm 3 - Mismatched double cord donors

Mycophenolate mofetil DRUG

15 mg/kg IV or orally bid and discontinued on Day +45 unless GVHD is present

Also known as: CellCept

Arm 1 - Matched sibling donor; Arm 2 - Matched unrelated donor; Arm 3 - Mismatched double cord donors

Intravenous immunoglobulin (IVIG) DRUG

500 mg/kg IV weekly beginning on Day +7 until Day +100

Arm 1 - Matched sibling donor; Arm 2 - Matched unrelated donor; Arm 3 - Mismatched double cord donors

Eligibility Criteria

• Age: Up to 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic; Lymphoproliferative Disorders; Chediak-Higashi Syndrome; Immunologic Deficiency Syndromes; Histiocytosis, Langerhans-Cell

Interventions

Stem Cell Transplantation; fludarabine; fludarabine phosphate; Melphalan; Antilymphocyte Serum; Alemtuzumab; Cyclosporine; Mycophenolic Acid; Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Albinism; Eye Diseases, Hereditary; Eye Diseases; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Immunoglobulin G; Immunoglobulin Isotypes

Results Point of Contact

• Title: Dr. Angela Smith
• Organization: Masonic Cancer Center, University of Minnesota

smith719@umn.edu

612-626-2778

Study Officials

• Angela Smith, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 15, 2005
• Study Start: August 1, 2002
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2014
• Last Updated: December 28, 2017
• Results First Posted: April 14, 2017

Record last verified: 2017-12

Locations

US (1)