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

Children's Hospital of Philadelphia (CHOP)

Status and phase: Active, not recruiting; Phase 2

Conditions: Non Malignant Diseases; Hemoglobinopathies; Immunodeficiencies

Treatments: Drug: RIC:Intermediate Campath; Drug: RIC: Distal Campath; Drug: RIC: Mini Busulfan

Study type: Interventional

Funder types: Other

Identifiers

NCT01050855

CHP 894 (Other Identifier)

08-005658

Details and patient eligibility

About

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.

Full 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.

Enrollment: 75 estimated patients

Sex: All

Ages: 6 months to 25 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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75 participants in 3 patient groups

RIC: Distal Campath

Experimental group

Description:

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

Treatment:

Drug: RIC: Distal Campath

RIC:Intermediate Campath

Experimental group

Description:

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

Treatment:

Drug: RIC:Intermediate Campath

RIC: Mini Busulfan

Experimental group

Description:

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

Treatment:

Drug: RIC: Mini Busulfan