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

June 23, 2026 updated by: Children's Hospital of Philadelphia
This Phase II pilot study evaluates the safety and effectiveness of reduced-intensity conditioning (RIC) regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric and young adult patients with non-malignant disorders, including immunodeficiencies and hemoglobinopathies. The study examines different conditioning approaches that vary in the timing and dosing of alemtuzumab (Campath), as well as disease-specific modifications for beta thalassemia major and infants. The primary objective is to assess donor engraftment and event-free survival at one year following transplant. The study aims to determine whether RIC regimens can reduce toxicity while maintaining successful engraftment and disease control.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This Phase II, single-institution, investigator-initiated pilot study evaluates reduced-intensity conditioning (RIC) strategies in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) for non-malignant disorders. The study focuses on optimizing conditioning approaches to balance adequate immunosuppression for donor engraftment with minimization of regimen-related toxicity.

RIC regimens are designed to reduce the organ toxicity and late effects associated with traditional myeloablative conditioning while maintaining sufficient host immune suppression to allow durable donor cell engraftment. This approach is particularly relevant in patients with pre-existing organ dysfunction or increased vulnerability to treatment-related complications. In non-malignant diseases, full donor chimerism may not be required for therapeutic benefit, and stable mixed chimerism may be sufficient for disease correction.

The conditioning strategies evaluated in this protocol primarily differ in the timing and administration of alemtuzumab, an anti-CD52 monoclonal antibody used to deplete host lymphocytes and reduce the risk of graft rejection and graft-versus-host disease. Earlier ("distal") administration is intended to reduce prolonged exposure at the time of stem cell infusion, thereby preserving donor immune function, while more proximal administration provides more immediate immunosuppression but may increase the risk of delayed immune recovery.

Disease-specific modifications to conditioning intensity are incorporated for select populations. Patients with beta thalassemia major receive additional cytoreductive and immunosuppressive agents to address the higher risk of graft rejection associated with intact immunity and expanded marrow space. Infants with immunodeficiencies are treated with modified regimens designed to reduce toxicity while maintaining engraftment potential.

Following conditioning, patients undergo stem cell transplantation using donor sources that may include related or unrelated donors as well as cord blood or alternative donor options based on clinical circumstances. Standard supportive care and post-transplant immunosuppression are administered according to institutional guidelines.

Patients are monitored longitudinally for engraftment, donor chimerism, immune recovery, and transplant-related complications. The study also evaluates clinical management strategies such as donor lymphocyte infusions or second transplantation in cases of declining chimerism or graft failure.

This study is intended to inform optimal conditioning approaches for patients with non-malignant disorders undergoing HSCT, with the goal of improving transplant tolerability while maintaining effective and durable engraftment.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • The Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age >6 months- 25 years

  2. Diseases eligible for Distal Alemtuzumab:

    • Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome
    • Sickle cell disease (Neurologic: history of stroke or any neurologic defect lasting >24 hours accompanied by infarct on MRI; or abnormal transcranial Doppler, or abnormal MRI with cerebral vasculature stenosis. OR minimum 2 episodes of acute chest syndrome in preceding 2 year period OR history 3 or more severe pain events/year in the 2 years prior to transplant.)
    • Thalassemia major
    • Bone marrow failure, including Kostmann's, amegakaryocytic thrombocytopenia, Blackfan-Diamond syndrome

  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%
    • Pulmonary: for those with pulmonary function tests: DLCO/VA >40% If DLCO/VA is not reported this is considered inability to perform the test. In this case Pulse Ox and Respiratory Exam will be used as evaluation criteria.
    • Renal: Serum creatinine <1.5 x upper limit of normal for age
    • Hepatic:; ALT and AST <5 x upper limit of normal
    • Infection: No active infections.

Exclusion criteria

  1. Uncontrolled bacterial, fungal or viral infections.
  2. Bare lymphocyte syndrome (MHC class II deficiency)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Reduced-Intensity Conditioning (RIC) HSCT
Participants receive reduced-intensity conditioning with alemtuzumab-, fludarabine-, and melphalan-based regimens, varying by timing of alemtuzumab (distal or intermediate). Regimens are based on established protocols used in non-malignant disorders. Alemtuzumab is administered prior to other agents to reduce risk of declining donor chimerism. Participants then undergo allogeneic stem cell transplantation with standard post-transplant care.
Drug: Reduced-Intensity Conditioning
A pre-transplant conditioning approach designed to provide sufficient immunosuppression to enable donor cell engraftment while minimizing regimen-related toxicity compared to myeloablative conditioning. Regimens are adapted based on patient age and underlying disease characteristics using the following agents: Campath, Fludarabine, Melphalan, Cyclosporine, Cellcept (MMF).
Other Names:
  • RIC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Engraftment
Time Frame: Post Transplant -100 days
engraftment of patients with non-malignant disorders will be evaluated using a reduced-intensity conditioning regimen
Post Transplant -100 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free Survival
Time Frame: 1 year post transplant
Event-free survival is defined as the time interval to either primary or late graft failure, disease recurrence, or death.
1 year post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital of Philadelphia

Investigators

  • Principal Investigator: Timothy J Olson, MD, Children's Hospital of Philadelphia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2008

Primary Completion (Actual)

July 1, 2024

Study Completion (Actual)

June 1, 2025

Study Registration Dates

First Submitted

January 15, 2010

First Submitted That Met QC Criteria

January 15, 2010

First Posted (Estimated)

January 18, 2010

Study Record Updates

Last Update Posted (Actual)

July 21, 2026

Last Update Submitted That Met QC Criteria

June 23, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-005658
  • CHP 894 (Other Identifier: Children's Hospital of Philadelphia)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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