Clinical trial NCT01050855: Reduced Intensity Conditioning (RIC) Regimen for Patients With Non-malignant Disorders
Official title: Reduced Intensity Conditioning (RIC) Regimen for Patients With Non-malignant Disorders
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non Malignant Diseases
Immunodeficiencies
Hemoglobinopathies
Keywords: Non-malignant diseases
Immune deficiencies
Hemoglobinopathies
Reduced Intensity Conditioning(RIC)
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
First posted: 2010-01-18
Enrollment: 75
Sex: ALL
Minimum age (years): 6
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Engraftment
timeFrame: Post Transplant -100 days
Secondary outcomes:
measure: Survival
timeFrame: 1 year post transplant
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Timothy J Olson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: King AA, Kamani N, Bunin N, Sahdev I, Brochstein J, Hayashi RJ, Grimley M, Abraham A, Dioguardi J, Chan KW, Douglas D, Adams R, Andreansky M, Anderson E, Gilman A, Chaudhury S, Yu L, Dalal J, Hale G, Cuvelier G, Jain A, Krajewski J, Gillio A, Kasow KA, Delgado D, Hanson E, Murray L, Shenoy S. Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies. Am J Hematol. 2015 Dec;90(12):1093-8. doi: 10.1002/ajh.24183. Epub 2015 Oct 6.