CompletedPhase 2

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

United States47 participantsStarted 2013-12

Plain-language 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.

Who can participate

Age range4 Months – 45 Years

SexALL

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Inclusion criteria

✓. Patient is ≥ 3 months and ≤ 45 years of age at time of enrollment.
✓. Meets criteria for one of the following immune disorders (2A-2F) requiring HCT:
✓. Cardiac: Left ventricular ejection fraction (LVEF) \> 40%; or LV shortening fraction (LVSF) \> 26% by echocardiogram.
✓. Renal: Calculated or radioisotope Glomerular Filtration Rate (GFR) \> 50 mL/min/1.73m\^2
✓. Hepatic: Adequate liver function: serum conjugated (direct) bilirubin \< 2x upper limit of normal for age as per local laboratory (with the exceptions of isolated hyperbilirubinemia due to Gilbert's syndrome, or hyperbilirubinemia as the result of liver inflammation in the setting of persistent, active HLH); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 10x upper limit of normal as per local laboratory (with the exception of elevated transaminase levels as the result of liver inflammation in the setting of persistent, active HLH).
✓. Pulmonary: Patient may not be on mechanical ventilation support or have progressive pulmonary infection at the time of transplant; Pulmonary Function Testing (PFT) with forced expiratory volume in one second (FEV1) \> 50% of normal and Diffusing capacity of the lung for carbon monoxide (DLCO) corrected for Hgb \> 50% of normal. Patients unable to undergo PFTs should have stable respiratory status with SaO2 \> 90% on a maximum of 2L/min supplemental oxygen.

Exclusion criteria

What they're measuring

Percentage of Participants With Overall Survival (OS)

Timeframe: 1 year and 18 months post-transplant

Trial details

NCT IDNCT01998633

SponsorMedical College of Wisconsin

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2016-09-23

Results submitted2018-03-29

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