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

Hemoglobinopathies Clinical Trial

— RIC  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01050855
• Other study ID #: 08-005658
• Secondary ID: CHP 894
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 2008
• Est. completion date: December 2026

Study information

• Verified date: February 2024
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemoglobinopathies
• Immunodeficiencies
• Non Malignant Diseases

Intervention

Drug:
• RIC: Distal Campath
Campath, Fludarabine, Melphalan, Cyclosporine, Cellcept (MMF)
• RIC:Intermediate Campath
Campath, Fludarabine, Melphalan, Cyclosporine, Cellcept (MMF)
• RIC: Mini Busulfan
Campath, Fludarabine, Busulfan, Cyclosporine, Cellcept (MMF)

Locations

Country	Name	City	State
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Engraftment	engraftment of patients with non-malignant disorders will be evaluated using a reduced-intensity conditioning regimen	Post Transplant -100 days
Secondary	Survival	Event free survival will be evaluated by the time interval to either the primary or late graft failure, disease recurrence or death.	1 year post transplant