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

Primary Purpose

Non Malignant Diseases, Immunodeficiencies, Hemoglobinopathies

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

RIC: Distal Campath

RIC:Intermediate Campath

RIC: Mini Busulfan

About this trial

This is an interventional treatment trial for Non Malignant Diseases focused on measuring Non-malignant diseases, Immune deficiencies, Hemoglobinopathies, Reduced Intensity Conditioning(RIC)

Eligibility Criteria

6 Months - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion criteria

1. Uncontrolled bacterial, fungal or viral infections

Sites / Locations

The Children's Hospital of PhiladelphiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

RIC: Distal Campath

RIC:Intermediate Campath

RIC: Mini Busulfan

Arm 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

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

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

Outcomes

Primary Outcome Measures

Engraftment

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

Secondary Outcome Measures

Survival

Event free survival will be evaluated by the time interval to either the primary or late graft failure, disease recurrence or death.

Full Information

NCT ID

NCT01050855

First Posted

January 15, 2010

Last Updated

March 8, 2023

Sponsor

Children's Hospital of Philadelphia

1. Study Identification

Unique Protocol Identification Number

NCT01050855

Brief Title

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

Acronym

RIC

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 2008 (undefined)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Children's Hospital of Philadelphia

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non Malignant Diseases, Immunodeficiencies, Hemoglobinopathies

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

RIC: Distal Campath

Arm Type

Experimental

Arm Description

Arm Title

RIC:Intermediate Campath

Arm Type

Experimental

Arm Description

Arm Title

RIC: Mini Busulfan

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

RIC: Distal Campath

Other Intervention Name(s)

Reduced Intensity Conditioning Regimen

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

RIC:Intermediate Campath

Other Intervention Name(s)

Reduced Intensity Conditioning Regimen

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

RIC: Mini Busulfan

Other Intervention Name(s)

Reduced Intensity Conditioning Regimen

Intervention Description

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

Primary Outcome Measure Information:

Title

Engraftment

Description

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

Time Frame

Post Transplant -100 days

Secondary Outcome Measure Information:

Title

Survival

Description

Event free survival will be evaluated by the time interval to either the primary or late graft failure, disease recurrence or death.

Time Frame

1 year post transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

25 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion criteria 1. Uncontrolled bacterial, fungal or viral infections

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Barbara McGlynn

Phone

215-590-1303

mcglynn@chop.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Patricia Hankins, RN

Phone

215-590-5168

hankinsp@chop.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Timothy J Olson, MD

Organizational Affiliation

Children's Hospital of Philadelphia

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Children's Hospital of Philadelphia

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Barbara McGlynn

Phone

215-590-1303

mcglynn@chop.edu

First Name & Middle Initial & Last Name & Degree

Patricia Hankins, RN

Phone

215 590-5168

hankinsp@chop.edu

First Name & Middle Initial & Last Name & Degree

Nancy J Bunin, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

26348869

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.

Results Reference

derived

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

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