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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Children's Hospital of Philadelphia
Sponsor:
Information provided by (Responsible Party):
Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01050855
First received: January 15, 2010
Last updated: June 20, 2016
Last verified: June 2016
  Purpose

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.


Condition Intervention Phase
Non Malignant Diseases
Immunodeficiencies
Hemoglobinopathies
Drug: RIC: Distal Campath
Drug: RIC:Intermediate Campath
Drug: RIC: Mini Busulfan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reduced Intensity Conditioning (RIC) Regimen for Patients With Non-malignant Disorders

Resource links provided by NLM:


Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • Engraftment and Survival [ Time Frame: Post Transplant -100 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: January 2008
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RIC: Distal Campath

Day Treatment

Day - 22 Inpatient: Alemtuzumab (Campath) test dose IV or SQ (subcutaneously) over 2 hours

Day - 21 to-19 Alemtuzumab IV/ SQ

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 Name: 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 Name: 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 Name: Reduced Intensity Conditioning Regimen

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 UK, and has been successful in a 3 month old infant at CHOP who engrafted with a haploidentical donor.

  Eligibility

Ages Eligible for Study:   6 Months to 25 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01050855

Contacts
Contact: Margaret T Tartaglione, RN 215-590-4029 tartaglione@email.chop.edu
Contact: Patricia Hankins, RN 215-590-5168 hankinsp@email.chop.edu

Locations
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Margaret Tartaglione, RN    215-590-2209    tartaglione@email.chop.edu   
Contact: Patricia Hankins, RN    215 590-5168    hankinsp@email.chop.edu   
Principal Investigator: Nancy J Bunin, MD         
Sponsors and Collaborators
Children's Hospital of Philadelphia
Investigators
Principal Investigator: Nancy J Bunin, MD Children's Hospital of Philadelphia
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01050855     History of Changes
Other Study ID Numbers: 08-005658  CHP 894 
Study First Received: January 15, 2010
Last Updated: June 20, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Children's Hospital of Philadelphia:
Non-malignant diseases
Immune deficiencies
Hemoglobinopathies
Reduced Intensity Conditioning(RIC)

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Hemoglobinopathies
Immune System Diseases
Hematologic Diseases
Genetic Diseases, Inborn
Fludarabine
Fludarabine phosphate
Alemtuzumab
Melphalan
Busulfan
Cyclosporins
Cyclosporine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on August 23, 2016