Blood and Marrow Clinical Trials Network (BMT CTN) Calcineurin Inhibitor-Free Interventions for Prevention of Graft-versus-Host Disease (1301)

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Accession Number

Study Type
Clinical Trial

Collection Type
Open BioLINCC Study See bottom of this webpage for request information

Study Period
August 2015 – October 2020

NHLBI Division

Dataset(s) Last Updated
September 29, 2023


Commercial Use Data Restrictions No

Data Restrictions Based On Area Of Research No


To compare chronic Graft-versus-Host Disease after hematopoietic cell transplant between each of the calcineurin inhibitor free interventions and a tacrolimus/methotrexate control in patients with hematologic malignancies.


Graft-versus-Host Disease (GVHD) is a common complication after allogeneic hematopoietic cell transplantation (HCT). The combination of a calcineurin inhibitor (CNI), such as tacrolimus (Tac), with methotrexate (MTX) has been the basis of most GVHD prophylaxis regimens worldwide. However, this standard approach does not effectively prevent chronic GVHD.

The incidence of chronic GVHD is affected by graft source, with mobilized peripheral blood stem cells (PBSC) having higher rates and more severe manifestations compared with bone marrow (BM) grafts. Recognition that GVHD is mediated by donor-derived T cells led to exploration of strategies for T-cell depletion that could be used in treatment plans. One approach involves CD34 selected T-cell depletion in peripheral blood stem cell (PBSC) grafts. Another approach involves infusion of BM grafts followed by post-transplant Cyclophosphamide (PTCy).

The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1301 trial was established to compare the CNI-free treatment plans for reduction of chronic GVHD to one another and to a Tac/MTX control in patients with HLA-matched donors.


Eligible patients were 65 years old or younger and about to undergo HLA-matched myeloablative HCT for treatment of acute leukemia in complete morphologic remission (CR), CR without hematologic recovery, or myelodysplastic syndrome (MDS) with <5% blasts in BM. HLA-matched related or unrelated donors were defined as 8 out of 8 matches at HLA-A, -B, -C and DRB1.

A total of 346 patients were enrolled. 114 patients were randomly assigned to the CD34 selected graft arm, 114 to the PTCy arm, and 118 to the Tac/MTX arm.


The BMT CTN 1301 trial was a three-arm Phase III randomized, multicenter unblinded study. Patients were randomly assigned using permuted blocks of random sizes and stratified by donor type (sibling vs. unrelated) and age (< 18, 18-40, and > 40 years).

Patients were randomly assigned to one of three specified interventions: (1) ex vivo CD34 selected T-cell–depleted PBSC graft without additional immunosuppression; donors were mobilized with granulocyte colony-stimulating factor according to institutional standards with a target CD34+ cell dose of ≥ 5 × 106 cells/kg; (2) unmanipulated BM graft followed by Cy 50 mg/kg on days +3 and +4 post-HCT; or (3) unmanipulated BM graft with post-HCT Tac and MTX. Tac was started on day –3 and dosed to maintain therapeutic levels between 5 and 15 ng/mL for a minimum of 90 days post-HCT. MTX was dosed at 15 mg/m2 intravenously (IV) at day +1 and 10 mg/m2 IV days +3, +6, and +11.

The primary end point of this trial was a composite of moderate to severe chronic GVHD, disease relapse, and survival (CRFS). Secondary end points included overall survival (OS), transplant-related mortality (TRM), infections, and health-related quality of life (QOL).


This study demonstrated that both experimental arms resulted in similar but not better outcomes compared with HCT using standard Tac and MTX with BM graft as measured by chronic GVHD-free relapse-free survival.

Luznik L, Pasquini MC, Logan B, et al. Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies. J Clin Oncol. 2022;40(4):356-368. doi:10.1200/JCO.21.02293

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