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Campath/Fludarabine/Melphalan Transplant Conditioning for Non-Malignant Diseases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00920972
Recruitment Status : Recruiting
First Posted : June 16, 2009
Last Update Posted : October 13, 2021
Sponsor:
Collaborator:
St. Louis Children's Hospital
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE June 15, 2009
First Posted Date  ICMJE June 16, 2009
Last Update Posted Date October 13, 2021
Study Start Date  ICMJE December 2001
Estimated Primary Completion Date December 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2019)
  • Donor engraftment as measured by chimerism [ Time Frame: 100 days post-transplant ]
    Engraftment is measured in myeloid and lymphoid lineage cells
  • Major toxicities as graded by the CTC v4 [ Time Frame: 100 days post-transplant ]
    Toxicity monitoring includes unanticipated side effects (new) and all severe irreversible toxicities Grade 3 and above unexpected Grade 4 and above - all toxicities that are possibly, probably or definitely related to protocol therapy All deaths irrespective of attribution
Original Primary Outcome Measures  ICMJE
 (submitted: June 15, 2009)
  • Donor engraftment as measured by chimerism [ Time Frame: 100 days post-transplant ]
  • Major toxicities as graded by the CTC v3 [ Time Frame: 100 days post-transplant ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2019)
  • Time to neutrophil and platelet engraftment as measured by complete blood counts [ Time Frame: Post transplant ]
    Defined as an ANC >500/microliter and platelets >20,000 or 50,000/microliter depending on disorder
  • Incidence of acute graft-versus-host disease as measured by protocol grading scale [ Time Frame: 100 days post-transplant ]
    aGVHD - involving the skin, gut and liver. Classified according to grading described by Thomas et al. NEJM 1975; 292:895-902
  • Incidence of chronic graft-versus-host disease as measured by protocol grading scale [ Time Frame: 2 years post-transplant ]
    cGVHD classified per Schulman et al. Am J Med 69: 204-17, 1980.
  • Long-term donor engraftment by donor chimerism [ Time Frame: 2 years post-transplant ]
    Donor chimerism is determined by PCR analysis after cell separation into lymphoid and myeloid lineage cells using antibodies. Can also be detected by FISH analysis in the event of donor and recipient sex discrepancy.
  • Immune reconstitution by laboratory evaluations [ Time Frame: 1 year post-transplant ]
    Immune reconstitution detected by absolute numbers of T cell phenotypes, B cells and NK cells. T cell function determined by proliferative response to mitogens. B cell function determined by evaluating anti-tetanus antibody titers.
  • Overall and disease free survival [ Time Frame: 2 years post-transplant ]
    Overall survival is defined as survival with or without disease Event free survival is defined as disease free, severe GVHD free survival, monitoring quality of life and relevant parameters.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2009)
  • Time to neutrophil and platelet engraftment as measured by complete blood counts [ Time Frame: Notapplicable ]
  • Incidence of acute graft-versus-host disease as measured by protocol grading scale [ Time Frame: 100 days post-transplant ]
  • Incidence of chronic graft-versus-host disease as measured by protocol grading scale [ Time Frame: 2 years post-transplant ]
  • Long-term donor engraftment by donor chimerism [ Time Frame: 2 years post-transplant ]
  • Immune reconstitution by laboratory evaluations [ Time Frame: 1 year post-transplant ]
  • Overall and disease free survival [ Time Frame: 2 years post-transplant ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Campath/Fludarabine/Melphalan Transplant Conditioning for Non-Malignant Diseases
Official Title  ICMJE A Study of Hematopoietic Stem Cell Transplantation (HSCT) in Non-Malignant Disease Using a Reduced-Intensity Preparatory Regime
Brief Summary The hypothesis for this study is that a preparative regimen that maximizes host immunosuppression without myeloablation will be well tolerated and sufficient for engraftment of donor hematopoietic cells. It is also to determine major toxicities from these conditioning regimens, within the first 100 days after transplantation.
Detailed Description

The study uses reduced intensity conditioning that is immune suppressive to achieve donor cell engraftment without exposure to radiation or high dose chemotherapy in children with non-malignant disorders. The intent is to minimize early and late regimen related toxicities in the context of a reduced intensity regimen.

In addition to maximizing opportunity for donor cell engraftment, the trial seeks to minimize toxicities associated with transplant such as graft versus host disease and employs GVHD prophylaxis that seeks to decrease rates of acute and chronic GVHD in the setting of matched and mismatched donor stem cell transplants from marrow and cord blood sources.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metabolic Disorders
  • Hematologic, Immune, or Bone Marrow Disorders
  • Hemoglobinopathies
  • Non-malignant Disorders
Intervention  ICMJE
  • Drug: Treatment Plan 1: Stratum 1
    Day -50 to -21: Hydroxyurea 30mg/kg PO q day Day -22: Campath-1H 3 mg IV or SQ... Day -21: Campath-1H 10 mg IV or SQ... Day -20: Campath-1H 15 mg IV or SQ... Day -19: Campath-1H 20 mg IV or SQ... Day -8: Fludarabine 30mg/m2 IV... Day -7: Fludarabine 30mg/m2 IV... Day -6: Fludarabine 30mg/m2 IV... Day -5: Fludarabine 30mg/m2 IV... Day -4: Fludarabine 30mg/m2 IV... Day -3: Melphalan 140 mg/m2 IV... (dose modifications for patients <10 kgs) Procedure/Surgery: Hematopoietic stem cell infusion on Day 0...
  • Drug: Treatment Plan 2: Strata 2, 3, or 4
    Day -50 to -21: Hydroxyurea 30mg/kg PO q day… Day -22: Campath-1H 3 mg IV or SQ... Day -21: Campath-1H 10 mg IV or SQ... Day -20: Campath-1H 15 mg IV or SQ... Day -19: Campath-1H 20 mg IV or SQ... Day -8: Fludarabine 30mg/m2 IV... Day -7: Fludarabine 30mg/m2 IV... Day -6: Fludarabine 30mg/m2 IV... Day -5: Fludarabine 30mg/m2 IV... Day -4: Fludarabine 30mg/m2 IV... Day -4: Thiotepa 8mg/kg IV… Day -3: Melphalan 140 mg/m2 IV... (dose modifications for patients <10 kgs) Procedure/Surgery: Hematopoietic stem cell infusion on day 0...
  • Drug: GVHD Regimen A: UCB Recipients
    Day -3: Begin Tacrolimus or cyclosporine Begin MMF Day -1: Abatacept 10mg/kg IV Day +5: Abatacept 10mg/kg IV Day +14: Abatacept 10mg/kg IV Day +28: Abatacept 10mg/kg IV Day +60: Abatacept 10mg/kg IV Day +100: Abatacept 10mg/kg IV
  • Drug: GVHD Regimen B: BM Recipients
    Day -3: Begin Tacrolimus or cyclosporine Begin MMF Day -1: Abatacept 10mg/kg IV Day +1: Methotrexate 7.5mg/m2 IV Day +3: Methotrexate 7.5mg/m2 IV Day +5: Abatacept 10mg/kg IV Day +6: Methotrexate 7.5mg/m2 IV Day +14: Abatacept 10mg/kg IV Day +28: Abatacept 10mg/kg IV Day +60: Abatacept 10mg/kg IV Day +100: Abatacept 10mg/kg IV Day +180: Abatacept 10mg/kg IV Day +270: Abatacept 10mg/kg IV Day +365: Abatacept 10mg/kg IV
Study Arms  ICMJE
  • Experimental: Stratum 1
    Recipients with non-malignant disorders, excluding thalassemia. Related or unrelated 8/8 HLA-matched bone marrow
    Interventions:
    • Drug: Treatment Plan 1: Stratum 1
    • Drug: GVHD Regimen B: BM Recipients
  • Experimental: Stratum 2
    Recipient with transfusion dependent thalassemia. Related or unrelated. 8/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
    Interventions:
    • Drug: Treatment Plan 2: Strata 2, 3, or 4
    • Drug: GVHD Regimen A: UCB Recipients
    • Drug: GVHD Regimen B: BM Recipients
  • Experimental: Stratum 3
    Recipient with hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
    Interventions:
    • Drug: Treatment Plan 2: Strata 2, 3, or 4
    • Drug: GVHD Regimen A: UCB Recipients
    • Drug: GVHD Regimen B: BM Recipients
  • Experimental: Stratum 4
    Recipient with non-malignant disorder, excluding hemoglobinopathy Related or unrelated. 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB
    Interventions:
    • Drug: Treatment Plan 2: Strata 2, 3, or 4
    • Drug: GVHD Regimen A: UCB Recipients
    • Drug: GVHD Regimen B: BM Recipients
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 15, 2014)
220
Original Estimated Enrollment  ICMJE
 (submitted: June 15, 2009)
107
Estimated Study Completion Date  ICMJE December 2031
Estimated Primary Completion Date December 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Stratum 1: Patient must have non-malignant disorder, excluding thalassemia. Must be receiving a 8/8 HLA-matched bone marrow, related or unrelated Stratum 2: Patient must have thalassemia receiving 8/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated.

Stratum 3: Patient must have a hemoglobinopathy receiving 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated.

Stratum 4: Patient must have a non-malignant disorder (excluding hemoglobinopathy) receiving 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated.

All strata:

  • Recipient age < 21 years
  • Lansky/Karnofsky >/= 40
  • Adequate pulmonary, renal, liver, and other organ function as defined in protocol
  • Negative pregnancy test
  • Adequate total nucleated cell or CD34+ dose of product as defined in protocol
  • If sickle cell, Hemoglobin S <30%

Exclusion Criteria:

  • HIV positive
  • Invasive infection
  • Pregnancy/lactating
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 20 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lisa Murray, MA, CCRP 3144544240 murraylm@wustl.edu
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00920972
Other Study ID Numbers  ICMJE 201110144
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Washington University School of Medicine
Original Responsible Party Shalini Shenoy, MD, Washington University School of Medicine
Current Study Sponsor  ICMJE Washington University School of Medicine
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE St. Louis Children's Hospital
Investigators  ICMJE
Principal Investigator: Shalini Shenoy, MD Washington University School of Medicine (in St. Louis)
PRS Account Washington University School of Medicine
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP