Reduced Intensity Conditioning for Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (BMT CTN 1204)

Summary

HLH, HLH-related disorders, Chronic Granulomatous (CGD), HIGM1, Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX) and severe LAD-I represent primary immune disorders that are typically fatal without Hematopoietic Cell Transplant (HCT). However, transplant is often complicated by inflammation, infection and other co-morbidities. In addition, these disorders have been shown to be cured with partial chimerism, making them an ideal target for the use of reduced intensity approaches, where a portion of patients may not achieve full donor chimerism, but instead achieve stable mixed chimerism. Reduced-intensity conditioning strategies have demonstrated improved survival with decreased Treatment Related Mortality (TRM) in institutional series for patients with HLH (Cooper et al., 2006; Marsh et al., 2010; Marsh et al., 2011). However, graft loss and unstable chimerism remain challenges. An institutional case series from Cincinnati Children's Hospital demonstrated full or high-level chimerism and improved durable engraftment using intermediate (Day -14) timing alemtuzumab (Marsh et al., 2013b). This study aims to test the efficacy of the Intermediate RIC strategy in a prospective multi-center study including HLH as well as other primary immunodeficiencies where allogeneic transplant with RIC has been shown to be feasible and stable chimerism is curative.

Conditions

• Hemophagocytic Lymphohistiocytosis
• Chronic Active Epstein-Barr Virus Infection
• Chronic Granulomatous Disease
• HIGM-1
• Leukocyte Adhesion Deficiency
• IPEX

Interventions

BIOLOGICAL

Hematopoietic Stem Cell Transplant

NOTE: The - sign is the number of days before the transplant and the + sign is the number of days after the transplant. * Alemtuzumab 0.2mg/kg Day-14,-13,-12,-11,-10 * Fludarabine 30 mg/m2 on Day -8,-7,-6,-5,-4 * Melphalan 140mg/m2 on Day -3 The GVHD prophylaxis will consist of the following: * Cyclosporine on Day -3 to Day +100, maintaining a level of 250-500 ng/mL, then taper to Day +180. * Methylprednisolone 2 mg/kg/day on Day -2 and -1, 1 mg/kg/day on Day 0 to Day +28, then taper over 1 month. Oral prednisone may be substituted starting on Day 0 (1.2 mg/kg/day)

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Blood and Marrow Transplant Clinical Trials Network

  collaborator NETWORK

• National Cancer Institute (NCI)

  collaborator NIH

• National Marrow Donor Program

  collaborator OTHER

• Medical College of Wisconsin

  lead OTHER

Principal Investigators

• Mary Horowitz, MD, MS · Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

4 Months

Max Age

45 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-12-31

Primary Completion

2016-09-23

Completion

2016-12-31

Countries

• United States
• Canada

Study Locations