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

Phase 2

Active, not recruiting

• Conditions: Non Malignant Diseases; Immunodeficiencies; Hemoglobinopathies

• Registration Number: NCT01050855
• Lead Sponsor: Children's Hospital of Philadelphia

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.

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 Timeline

• Study Start: 2008-01
• Study First Submitted: 2010-01-15
• Study First Submitted QC: 2010-01-15
• Study First Posted: 2010-01-18
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-24
• Last Update Posted: 2024-07-25
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 75

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Engraftment	Post Transplant -100 days	engraftment of patients with non-malignant disorders will be evaluated using a reduced-intensity conditioning regimen

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States