A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation.

dc.contributor.author

Arai, Sally

dc.contributor.author

Pidala, Joseph

dc.contributor.author

Pusic, Iskra

dc.contributor.author

Chai, Xiaoyu

dc.contributor.author

Jaglowski, Samantha

dc.contributor.author

Khera, Nandita

dc.contributor.author

Palmer, Jeanne

dc.contributor.author

Chen, George L

dc.contributor.author

Jagasia, Madan H

dc.contributor.author

Mayer, Sebastian A

dc.contributor.author

Wood, William A

dc.contributor.author

Green, Michael

dc.contributor.author

Hyun, Teresa S

dc.contributor.author

Inamoto, Yoshihiro

dc.contributor.author

Storer, Barry E

dc.contributor.author

Miklos, David B

dc.contributor.author

Shulman, Howard M

dc.contributor.author

Martin, Paul J

dc.contributor.author

Sarantopoulos, Stefanie

dc.contributor.author

Lee, Stephanie J

dc.contributor.author

Flowers, Mary ED

dc.coverage.spatial

United States

dc.date.accessioned

2016-08-01T17:02:19Z

dc.date.issued

2016-01-15

dc.description.abstract

PURPOSE: Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. EXPERIMENTAL DESIGN: We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m(2) i.v. weekly × 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary endpoints included changes of B-cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and nonresponders with each therapy. RESULTS: SCR was observed in 9 of 35 [26%; 95% confidence interval (CI); 13%-43%] participants randomized to imatinib and 10 of 37 (27%; 95% CI, 14%-44%) randomized to rituximab. Six (17%; 95% CI, 7%-34%) patients in the imatinib arm and 5 (14%; 95% CI, 5%-29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27(+)) were seen at enrollment in rituximab-treated patients who had treatment success (P = 0.01), but not in imatinib-treated patients. CONCLUSIONS: These results support the need for more effective therapies for cutaneous sclerosis and suggest that activated B cells define a subgroup of patients with cutaneous sclerosis who are more likely to respond to rituximab.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/26378033

dc.identifier

1078-0432.CCR-15-1443

dc.identifier.issn

1078-0432

dc.identifier.uri

https://hdl.handle.net/10161/12562

dc.language

eng

dc.publisher

American Association for Cancer Research (AACR)

dc.relation.ispartof

Clin Cancer Res

dc.relation.isversionof

10.1158/1078-0432.CCR-15-1443

dc.subject

Adult

dc.subject

Aged

dc.subject

Antigens, CD27

dc.subject

B-Lymphocytes

dc.subject

Cross-Over Studies

dc.subject

Female

dc.subject

Graft vs Host Disease

dc.subject

Hematopoietic Stem Cell Transplantation

dc.subject

Humans

dc.subject

Imatinib Mesylate

dc.subject

Male

dc.subject

Middle Aged

dc.subject

Prospective Studies

dc.subject

Rituximab

dc.subject

Sclerosis

dc.subject

Skin Diseases

dc.subject

Young Adult

dc.title

A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation.

dc.type

Journal article

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/26378033

pubs.begin-page

319

pubs.end-page

327

pubs.issue

2

pubs.organisational-group

Basic Science Departments

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Duke

pubs.organisational-group

Duke Cancer Institute

pubs.organisational-group

Immunology

pubs.organisational-group

Institutes and Centers

pubs.organisational-group

Medicine

pubs.organisational-group

Medicine, Cellular Therapy

pubs.organisational-group

School of Medicine

pubs.publication-status

Published

pubs.volume

22

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Arai_Sarantopoulos_CCR_2016_imatinib study.pdf
Size:
635.63 KB
Format:
Adobe Portable Document Format