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

Brief Title

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

Official Title

In-vivo T-cell Depletion and Hematopoietic Stem Cell Transplantation for Life-Threatening Immune Deficiencies and Histiocytic Disorders

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.

Detailed Description

      Subjects will begin chemotherapy as a preparative regimen, which is intended to completely
      eliminate their defective immune system and bone marrow. The preparative regimen consists of
      the chemotherapy drugs (busulfan, cyclophosphamide, and antithymocyte globulin (ATG)).

      Transplantation: subjects will then have a source of blood stem cells (bone marrow) from
      their donor administered into their catheter. Medication will be given to help prevent
      Graft-Versus Host Disease (GVHD). The ATG will help to deplete the donor stem cells of the
      type of cells that can cause GVHD and will also help to promote engraftment of the new stem

      Recovery Phase: The second phase of treatment consists of a period after transplantation
      during which we wait for the return of bone marrow function. This usually takes two to four
      weeks. Subjects will be given a blood cell growth factor, G-CSF, to help speed recovery of
      the white blood cells and potentially decrease the risk of infection and decrease the time
      until the bone marrow recovers.

Study Phase

Phase 2/Phase 3

Study Type


Primary Outcome

Time to Transplant Engraftment

Secondary Outcome

 Number of Patients With Treatment Related Mortality.


Hemophagocytic Lymphohistiocytosis


Stem Cell Transplant

Study Arms / Comparison Groups

Description:  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.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

September 2000

Completion Date

August 2015

Primary Completion Date

August 2012

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  Patients meeting clinical diagnostic criteria or genetic diagnosis of X-linked
             lymphoproliferative disorder (XLP) and whose disease is ACTIVE but STABLE, or

          -  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

          -  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:

               -  Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction
                  at rest must be > 40% and must improve with exercise, or shortening fraction by
                  echocardiogram must be within institutional normals

               -  Hepatic: < 3 x normal SGOT and < 2.5 mg/dL serum bilirubin

               -  Renal: Serum creatinine within normal range, or if serum creatinine outside
                  normal range then creatinine clearance or glomerular filtration study should be >
                  50% of normal.

               -  Pulmonary: Asymptomatic or, if symptomatic, diffusing capacity of the lung for
                  carbon monoxide (DLCO) > 45% of predicted (corrected for hemoglobin). For
                  children unable to perform pulmonary function testing, then oxygen saturation
                  should be >95%.

          -  Availability of a suitable allogeneic bone marrow donor as per current institutional
             guidelines for non-T cell depleted hematopoietic stem cell transplant (HSCT).

          -  Patients who have undergone previous stem cell transplant (SCT) and failed engraftment
             or who had relapse of their disease are considered eligible if they meet other
             eligibility criteria and if the second SCT would occur 6 months or more after the
             first. If the first SCT preparative regimen was of a non-myeloablative intensity then
             the second SCT could be performed earlier when the acute toxicity from that procedure
             was resolved.

        Exclusion Criteria:

          -  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.




N/A - 55 Years

Accepts Healthy Volunteers



Angela Smith, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Masonic Cancer Center, University of Minnesota

Study Sponsor

Angela Smith, MD, Principal Investigator, University of Minnesota Medical Center

Verification Date

May 2015