Stem Cell Transplant for Immunologic or Histiocytic Disorders

NCT ID: NCT00176865

Last Updated: 2017-12-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-08-31

Study Completion Date

2014-08-31

Brief Summary

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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).

Detailed Description

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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.

Conditions

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

Keywords

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Stem cell transplant immunodeficiency donor lymphocyte infusion

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1 - Matched sibling donor

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)

Group Type ACTIVE_COMPARATOR

Stem Cell Transplant

Intervention Type PROCEDURE

IV on Day 0

Fludarabine

Intervention Type DRUG

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

Melphalan

Intervention Type DRUG

140 mg/m\^2 IV Day -1

Anti-thymocyte globulin (ATG)

Intervention Type DRUG

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

Campath 1H

Intervention Type 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

Cyclosporin A

Intervention Type 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

Mycophenolate mofetil

Intervention Type DRUG

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

Intravenous immunoglobulin (IVIG)

Intervention Type DRUG

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

Arm 2 - Matched unrelated donor

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)

Group Type ACTIVE_COMPARATOR

Stem Cell Transplant

Intervention Type PROCEDURE

IV on Day 0

Fludarabine

Intervention Type DRUG

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

Melphalan

Intervention Type DRUG

140 mg/m\^2 IV Day -1

Anti-thymocyte globulin (ATG)

Intervention Type DRUG

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

Campath 1H

Intervention Type 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

Cyclosporin A

Intervention Type 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

Mycophenolate mofetil

Intervention Type DRUG

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

Intravenous immunoglobulin (IVIG)

Intervention Type DRUG

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

Arm 3 - Mismatched double cord donors

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)

Group Type ACTIVE_COMPARATOR

Stem Cell Transplant

Intervention Type PROCEDURE

IV on Day 0

Fludarabine

Intervention Type DRUG

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

Melphalan

Intervention Type DRUG

140 mg/m\^2 IV Day -1

Anti-thymocyte globulin (ATG)

Intervention Type DRUG

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

Campath 1H

Intervention Type 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

Cyclosporin A

Intervention Type 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

Mycophenolate mofetil

Intervention Type DRUG

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

Intravenous immunoglobulin (IVIG)

Intervention Type DRUG

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

Interventions

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Stem Cell Transplant

IV on Day 0

Intervention Type PROCEDURE

Fludarabine

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

Intervention Type DRUG

Melphalan

140 mg/m\^2 IV Day -1

Intervention Type DRUG

Anti-thymocyte globulin (ATG)

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

Mycophenolate mofetil

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

Intervention Type DRUG

Intravenous immunoglobulin (IVIG)

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

Intervention Type DRUG

Other Intervention Names

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hematopoietic stem cell transplant Fludara Alkeran ATGAM Alemtuzumab CellCept

Eligibility Criteria

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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
Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Angela Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

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Masonic Cancer Center University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

Other Identifiers

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0207M29448

Identifier Type: OTHER

Identifier Source: secondary_id

MT2002-12

Identifier Type: -

Identifier Source: org_study_id