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

NCT01050855 | Active Not Recruiting Phase 2

• 2 other identifiers: 08-005658CHP 894
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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.

Conditions

Non Malignant Diseases; Immunodeficiencies; Hemoglobinopathies

Keywords

Non-malignant diseases; Immune deficiencies; Hemoglobinopathies; Reduced Intensity Conditioning(RIC)

Outcome Measures

Primary Outcomes (1)

• Engraftment

  engraftment of patients with non-malignant disorders will be evaluated using a reduced-intensity conditioning regimen

  Post Transplant -100 days

Secondary Outcomes (1)

• Survival

  1 year post transplant

Study Arms (3)

RIC: Distal Campath

EXPERIMENTAL

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

RIC:Intermediate Campath

EXPERIMENTAL

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

RIC: Mini Busulfan

EXPERIMENTAL

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

Interventions

RIC: Distal Campath DRUG

Campath, Fludarabine, Melphalan, Cyclosporine, Cellcept (MMF)

Also known as: Reduced Intensity Conditioning Regimen

RIC: Distal Campath

RIC:Intermediate Campath DRUG

Campath, Fludarabine, Melphalan, Cyclosporine, Cellcept (MMF)

Also known as: Reduced Intensity Conditioning Regimen

RIC:Intermediate Campath

RIC: Mini Busulfan DRUG

Campath, Fludarabine, Busulfan, Cyclosporine, Cellcept (MMF)

Also known as: Reduced Intensity Conditioning Regimen

RIC: Mini Busulfan

Eligibility Criteria

• Age: 6 Months - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age \>6 months- 25 years
• Diseases eligible for Distal Alemtuzumab:
• Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome
• Sickle cell disease
• Thalassemia major
• Bone marrow failure
• 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
• 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
• No active infections

You may not qualify if:

• \. Uncontrolled bacterial, fungal or viral infections

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 26348869 DERIVED

MeSH Terms

Conditions

Immunologic Deficiency Syndromes; Hemoglobinopathies

Condition Hierarchy (Ancestors)

Immune System Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Timothy J Olson, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2010
• First Posted: January 18, 2010
• Study Start: January 1, 2008
• Primary Completion: July 1, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (1)