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Reduced Intensity Conditioning (RIC) Regimen for Patients With Non-malignant Disorders

Sponsor
Children's Hospital of Philadelphia (Other)
Overall Status
Recruiting
CT.gov ID
NCT01050855
Collaborator
(none)
50
Enrollment
1
Location
3
Arms
203
Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase II pilot study to evaluate engraftment and toxicity of patients with non-malignant diseases using a reduced intensity conditioning regimen in the setting of allogeneic transplant for non malignant diseases. Bone Marrow or cord blood will be acceptable as a stem cell source.

Recently, reduced intensity conditioning (RIC) regimens have been used for both adult patients with leukemias and pediatric patients with non-malignant diseases. These regimens are better tolerated, resulting in less transplant related morbidity and mortality. Stable mixed chimerism, while insufficient for eradication of leukemias, may be sufficient to cure patients with non-malignant diseases.

Condition or Disease Intervention/Treatment Phase
  • Drug: RIC: Distal Campath
  • Drug: RIC:Intermediate Campath
  • Drug: RIC: Mini Busulfan
 Phase 2

Detailed Description

There are two conditioning regimens in this protocol for children >6 months. Alemtuzumab (Campath), Fludarabine and Melphalan are used. The regimens differ by the timing and dosing of Alemtuzumab (Campath). The two timings are distal and intermediate.

  • Distal campath is initiated 22 days prior to the allogeneic transplant.

  • Intermediate campath is initiated 14 days prior to allogeneic transplant.

The conditioning regimen for children with immunodeficiencies <6 months omits melphalan, and substitutes two days of busulfan. This regimen is successfully used in the United Kingdom, and has been successful in a 3 month old infant at the Children's Hospital of Philadelphia (CHOP) who engrafted with a haploidentical donor.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Reduced Intensity Conditioning (RIC) Regimen for Patients With Non-malignant Disorders
Study Start Date :
Jan 1, 2008
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Dec 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: RIC: Distal Campath

Day Treatment Day - 22 Inpatient: Alemtuzumab (Campath) test dose IV or SQ (subcutaneously) (subcutaneously) over 2 hours Day - 21 to-19 Alemtuzumab IV/ SQ (subcutaneously) Day - 7 to -3 Readmission to hospital Fludarabine IV Day - 2 Melphalan IV Day - 1 Begin cyclosporine infusion Day 0 Transplant: Bone marrow or cord blood infusion

Drug: RIC: Distal Campath
Campath, Fludarabine, Melphalan, Cyclosporine, Cellcept (MMF)
Other Names:
  • Reduced Intensity Conditioning Regimen

    		•
    Experimental: RIC:Intermediate Campath

    Day Treatment Day - 14 to-10 Inpatient: Alemtuzumab (Campath) IV or SQ (subcutaneously) Day - 7 to -3 Fludarabine IV Day - 2 Melphalan 140 mg/m2 IV Day - 1 Cyclosporine infusion starts Day 0 Transplant: Bone marrow or cord blood infusion

    Drug: RIC:Intermediate Campath
    Campath, Fludarabine, Melphalan, Cyclosporine, Cellcept (MMF)
    Other Names:
  • Reduced Intensity Conditioning Regimen

    		•
    Experimental: RIC: Mini Busulfan

    Day Treatment Day - 8 Alemtuzumab (Campath) IV or SQ (subcutaneously) Day - 7 Alemtuzumab (Campath) IV or SQ (subcutaneously) Day - 6 Alemtuzumab (Campath) IV or SQ (subcutaneously) Busulfan IV Fludarabine IV Day - 5 Alemtuzumab (Campath) IV or SQ (subcutaneously) Busulfan IV Fludarabine IV Day - 4 Alemtuzumab (Campath) IV or SQ (subcutaneously) Fludarabine IV Day - 3 Fludarabine IV Day - 2 Fludarabine IV Cyclosporine infusion Day - 1 Rest Day 0 Transplant: Bone marrow or cord blood infusion

    Drug: RIC: Mini Busulfan
    Campath, Fludarabine, Busulfan, Cyclosporine, Cellcept (MMF)
    Other Names:
  • Reduced Intensity Conditioning Regimen

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Engraftment [Post Transplant -100 days]

      engraftment of patients with non-malignant disorders will be evaluated using a reduced-intensity conditioning regimen

    Secondary Outcome Measures

    1. Survival [1 year post transplant]

      Event free survival will be evaluated by the time interval to either the primary or late graft failure, disease recurrence or death.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Months to 25 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Age >6 months- 25 years

    2. Diseases eligible for Distal Alemtuzumab:

    • Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome

    • Sickle cell disease

    • Thalassemia major

    • Bone marrow failure

    1. Diseases eligible for Intermediate Alemtuzumab

    • Hemophagocytic lymphohistiocytosis other macrophage activation syndromes, severe Langerhans histiocytosis

    • Severe combined immune deficiency, adenosine deaminase deficiency, common variable immunodeficiency

    • Wiskott-Aldrich syndrome

    1. Organ criteria:

    • Cardiac: Echocardiogram shortening fraction >27%

    • Renal: Serum creatinine less than 1.5 times the upper limit of normal for age

    • Hepatic: liver function tests must be less than 5 times the upper limit of normal

    1. No active infections

    Exclusion criteria

    1. Uncontrolled bacterial, fungal or viral infections

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104

    Sponsors and Collaborators

    • Children's Hospital of Philadelphia

    Investigators

    • Principal Investigator: Timothy J Olson, MD, Children's Hospital of Philadelphia

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Children's Hospital of Philadelphia
    ClinicalTrials.gov Identifier:
    NCT01050855
    Other Study ID Numbers:
    • 08-005658
    • CHP 894
    First Posted:
    Jan 18, 2010
    Last Update Posted:
    Mar 23, 2022
    Last Verified:
    Mar 1, 2022
    Keywords provided by Children's Hospital of Philadelphia
    Non-malignant diseases
    Immune deficiencies
    Hemoglobinopathies
    Reduced Intensity Conditioning(RIC)
    Additional relevant MeSH terms:
    Hemoglobinopathies
    Busulfan
    Alemtuzumab

    Study Results

    No Results Posted as of Mar 23, 2022