Abstract |
CXCR4 directs chronic lymphocytic leukemia (CLL) trafficking within protective tissue niches, and targeting CXCR4 with plerixafor may enhance drug sensitivity. We performed a phase 1 dose escalation study of plerixafor (NCT00694590) with rituximab in 24 patients with relapsed/refractory CLL. Patients received rituximab 375 mg/m2 on days 1, 3, and 5, followed by bi-weekly rituximab plus dose-escalated plerixafor for 4 weeks. The maximum tolerated dose of plerixafor was 320 µg/kg. The most common toxicities were fatigue (13 patients, 57%), nausea (11, 48%), chills (10, 43%), and diarrhea and dyspnea (seven, 30% each). No patients developed symptomatic hyperleukocytosis or tumor lysis syndrome. A median 3.3-fold increase (range 1.2-12.4) in peripheral blood CLL was seen following the first dose of plerixafor, confirming CLL cell mobilization. The overall response rate was 38% and correlated with higher doses of plerixafor. Plerixafor is well-tolerated in patients with CLL; further tumor sensitization studies with CXCR4 antagonists are warranted.
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Authors | Leslie A Andritsos, John C Byrd, Peter Cheverton, Jingyang Wu, Mariela Sivina, Thomas J Kipps, Jan A Burger |
Journal | Leukemia & lymphoma
(Leuk Lymphoma)
Vol. 60
Issue 14
Pg. 3461-3469
(12 2019)
ISSN: 1029-2403 [Electronic] United States |
PMID | 31352850
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzylamines
- Cyclams
- Heterocyclic Compounds
- Rituximab
- plerixafor
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Combined Chemotherapy Protocols
(pharmacokinetics, therapeutic use)
- Benzylamines
- Cyclams
- Female
- Follow-Up Studies
- Heterocyclic Compounds
(administration & dosage)
- Humans
- Leukemia, Lymphocytic, Chronic, B-Cell
(drug therapy, pathology)
- Male
- Maximum Tolerated Dose
- Middle Aged
- Prognosis
- Rituximab
(administration & dosage)
- Survival Rate
- Tissue Distribution
- Young Adult
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