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

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ClinicalTrials.gov Identifier: NCT01050855
Recruitment Status : Recruiting
First Posted : January 18, 2010
Last Update Posted : March 10, 2023
Sponsor:
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Study Description
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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
Non Malignant Diseases Immunodeficiencies Hemoglobinopathies 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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 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 : January 2008
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: 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 Name: Reduced Intensity Conditioning Regimen


Outcome Measures
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Primary Outcome Measures :
  1. Engraftment [ Time Frame: 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 [ Time Frame: 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
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Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

  3. 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

  4. 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
  5. No active infections

Exclusion criteria

1. Uncontrolled bacterial, fungal or viral infections

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01050855


Contacts
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Contact: Barbara McGlynn 215-590-1303 mcglynn@chop.edu
Contact: Patricia Hankins, RN 215-590-5168 hankinsp@chop.edu

Locations
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United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Barbara McGlynn    215-590-1303    mcglynn@chop.edu   
Contact: Patricia Hankins, RN    215 590-5168    hankinsp@chop.edu   
Principal Investigator: Nancy J Bunin, MD         
Sponsors and Collaborators
Children's Hospital of Philadelphia
Investigators
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Principal Investigator: Timothy J Olson, MD Children's Hospital of Philadelphia
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01050855    
Other Study ID Numbers: 08-005658
CHP 894 ( Other Identifier: Children's Hospital of Philadelphia )
First Posted: January 18, 2010    Key Record Dates
Last Update Posted: March 10, 2023
Last Verified: March 2023
Keywords provided by Children's Hospital of Philadelphia:
Non-malignant diseases
Immune deficiencies
Hemoglobinopathies
Reduced Intensity Conditioning(RIC)
Additional relevant MeSH terms:
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Hemoglobinopathies
Hematologic Diseases
Genetic Diseases, Inborn
Busulfan
Alemtuzumab
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
 Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological