T-Cell Depletion and Stem Cell Transplant for Immune Deficiencies and Histiocytic Disorders

NCT00176826 | Terminated Phase 2 Results DMC

• 2 other identifiers: UMN-MT2000-210010M66781
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The hypothesis is to determine if a preparative regimen of busulfan, cyclophosphamide, and antithymocyte globulin (ATG) plus allogeneic stem cell transplantation will be effective in the treatment of immune deficiencies and histiocytic disorders.

Conditions

Hemophagocytic Lymphohistiocytosis; X-Linked Lymphoproliferative Disorders; Chediak-Higashi Syndrome; Griscelli Syndrome; Immunologic Diseases; Langerhans-Cell Histiocytosis; Hematologic Diseases

Keywords

Stem Cell Transplant; T-cell depletion; immune deficiencies; Busulfan pharmacokinetics; Non-Malignant Hematological Disorders

Outcome Measures

Primary Outcomes (1)

• Time to Transplant Engraftment

  Day 100 Post Transplant

Secondary Outcomes (6)

• Number of Patients With Treatment Related Mortality.

  Day 100 Post Transplant

• Number of Patients Surviving (Disease-free)

  1 year

• Number of Patients With Grade II-IV Graft-Versus-Host Disease (GVHD)

  Day 100 Post Transplant

• Number of Patients With Graft Failure

  Day 100 Post transplant

• Number of Patients With III-IV Graft-Versus-Host Disease (GVHD)

  Day 100 Post Transplant

Study Arms (1)

Intent-To-Treat

EXPERIMENTAL

Patients who were treated with chemotherapies (myeloablative conditioning regimen) and stem cell transplant. Busulfan intravenously for 4 days followed by cyclophosphamide intravenously for 4 days. Rabbit ATG is given intravenously for 4 doses pre-transplant.

Procedure: Stem Cell Transplant; Drug: Myeloablative conditioning regimen

Interventions

Stem Cell Transplant PROCEDURE

Infusion of hematopoietic stem cells (bone marrow, cord blood, peripheral blood stem cells) following myeloablative conditioning regimen.

Also known as: HSCT

Intent-To-Treat

Myeloablative conditioning regimen DRUG

Busulfan intravenously for 4 days followed by cyclophosphamide intravenously for 4 days. Rabbit ATG is given intravenously for 4 doses pre-transplant.

Also known as: Busulfex, Cytoxan, ATG

Intent-To-Treat

Eligibility Criteria

• Age: Up to 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Any patient from birth to \< 55 years of age fulfilling the following criteria will be eligible for this study.
• Patients meeting clinical diagnostic criteria for Hemophagocytic Lymphohistiocytosis (HLH)
• Patients meeting clinical diagnostic criteria or genetic diagnosis of X-linked lymphoproliferative disorder (XLP) and whose disease is ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT.
• Patients with Chediak-Higashi Syndrome who meet the following diagnostic criteria and whose disease is ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT as defined in Appendix V of the study protocol.
• Patients with Viral Associated Hemophagocytic Syndrome (VAHS) - if relapsed after other therapy or supportive care. Diagnostic criteria as above for HLH. Disease status must be ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT as defined in Appendix V. It is cautioned that many patients with HLH or familial hemophagocytic lymphohistiocytosis (FHL) will have a viral infection at time of initial presentation and may therefore be misdiagnosed as having VAHS.
• Griscelli Syndrome
• Primary immune deficiencies with non-genotypic identical donors only.
• Progressive Langerhans cell histiocytosis unresponsive to standard therapy.
• Other non-malignant hematological disorders in which stem cell transplant with a myeloablative regimen is indicated.
• Diamond Blackfan Anemia if transfusion dependent
• Schwachman Diamond Syndrome: with cytopenias or transformation to myelodysplastic syndrome (MDS)
• Kostman's Syndrome (if ANC \<500 without GCSF support, or transformation to MDS)
• Congenital dyserythropoietic anemia if transfusion dependent
• Amegakaryocytic thrombocytopenia if baseline platelet counts \<20,000 or requiring transfusions.
• Cardiac, hepatic, renal and pulmonary function deemed adequate for high dose chemotherapy with stem cell rescue as per institutional standards. General guidelines are as follows:

You may not qualify if:

• Patients who are moribund or whose life expectancy is severely limited by disease other than their underlying disorder. Karnofsky performance status \< 70% or Lansky \< 50% for patients \< 16 years.
• Patients with hemophagocytic disorders secondary to underlying malignancy.
• Patients who have ACTIVE/UNSTABLE disease as defined in Appendix V.
• Significant active infections, including Human Immunodeficiency Virus (HIV).
• Age \> 55 years.
• Not providing informed consent.

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; Immune System Diseases; Histiocytosis, Langerhans-Cell; Hematologic Diseases

Interventions

Stem Cell Transplantation; Busulfan; Cyclophosphamide

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Albinism; Eye Diseases, Hereditary; Eye Diseases; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; 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; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Angela Smith
• Organization: University of Minnesota

smith719@umn.edu

612-626-2778

Study Officials

• Angela Smith, MD

  University of Minnesota Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 15, 2005
• Study Start: September 1, 2000
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2015
• Last Updated: January 23, 2018
• Results First Posted: April 28, 2014

Record last verified: 2015-05

Locations

US (1)