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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Children's Hospital of Philadelphia
Sponsor:
Information provided by (Responsible Party):
Nancy Bunin, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT01050855
First received: January 15, 2010
Last updated: October 22, 2014
Last verified: October 2014
  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: November 2016
Estimated Primary Completion Date: November 2015 (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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age >6 months- 25 years
  2. IPEX syndrome
  3. Sickle cell disease
  4. Thalassemia major
  5. Bone marrow failure, including Kostmann's, amegakaryocytic thrombocytopenia, Blackfan-Diamond syndrome
  6. Hemophagocytic lymphohistiocytosis other macrophage activation syndromes, severe Langerhans histiocytosis
  7. Severe combined immune deficiency, adenosine deaminase deficiency, common variable immunodeficiency
  8. Wiskott-Aldrich syndrome
  9. Age <6 months with immunodeficiencies: Eligible for "mini" busulfan, fludarabine, alemtuzumab
  10. Organ criteria:

    • Cardiac: Echocardiogram shortening fraction >27%
    • Pulmonary: for those with pulmonary function tests: DLCO >40%
    • Renal: Serum creatinine <1.5 x upper limit of normal for age
    • Hepatic:; ALT and AST <5 x upper limit of normal
  11. Infection: No active infections

Exclusion criteria

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

No publications provided

Responsible Party: Nancy Bunin, BMT Medical Director, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT01050855     History of Changes
Other Study ID Numbers: 2008-1-5658, CHP 894
Study First Received: January 15, 2010
Last Updated: October 22, 2014
Health Authority: 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:
Hemoglobinopathies
Immunologic Deficiency Syndromes
Genetic Diseases, Inborn
Hematologic Diseases
Immune System Diseases
Alemtuzumab
Busulfan
Cyclosporine
Cyclosporins
Fludarabine
Alkylating Agents
Anti-Infective Agents
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014