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

February 23, 2024 updated by: Children's Hospital of Philadelphia

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

75

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
    • 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

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RIC: Distal Campath

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
Campath, Fludarabine, Melphalan, Cyclosporine, Cellcept (MMF)
Other Names:
  • Reduced Intensity Conditioning Regimen
Experimental: RIC:Intermediate Campath

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
Campath, Fludarabine, Melphalan, Cyclosporine, Cellcept (MMF)
Other Names:
  • Reduced Intensity Conditioning Regimen
Experimental: RIC: Mini Busulfan

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
Campath, Fludarabine, Busulfan, Cyclosporine, Cellcept (MMF)
Other Names:
  • Reduced Intensity Conditioning Regimen

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
Survival
Time Frame: 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.
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

January 1, 2008

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2026

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 (Estimated)

February 28, 2024

Last Update Submitted That Met QC Criteria

February 23, 2024

Last Verified

February 1, 2024

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)

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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