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BL-8040 CXCR4 antagonist is safe and demonstrates antileukemic activity in combination with cytarabine for the treatment of relapsed/refractory acute myelogenous leukemia: An open-label safety and efficacy phase 2a study.
- Source :
-
Cancer [Cancer] 2021 Apr 15; Vol. 127 (8), pp. 1246-1259. Date of Electronic Publication: 2020 Dec 03. - Publication Year :
- 2021
-
Abstract
- Background: CXCR4 mediates the retention and survival of acute myelogenous leukemia blasts in bone marrow and contributes to their resistance to chemotherapy. The authors evaluated a combination of the high-affinity CXCR4 antagonist BL-8040 with high-dose cytarabine (HiDAC) chemotherapy in a phase 2a study of patients with relapsed and refractory AML.<br />Methods: Forty-two patients received treatment with BL-8040 monotherapy for 2 days followed by a combination of BL-8040 with HiDAC for 5 days. Six escalating BL-8040 dose levels were investigated (0.5, 0.75, 1.0, 1.25, 1.5, and 2.0 mg/kg), and 1.5 mg/kg was selected as the dose for the expansion phase (n = 23).<br />Results: BL-8040 in combination with HiDAC was safe and well tolerated at all dose levels. Clinical response was observed with BL-8040 doses ≥1.0 mg/kg. The composite response rate (complete remissions plus complete remissions with incomplete hematologic recovery of platelets or neutrophils) was 29% (12 of 42) in all patients and 39% (9 of 23) in the 1.5-mg/kg phase. The median overall survival was 8.4 months for all patients, 10.8 months in the 1.5-mg/kg phase, and 21.8 months for responding patients in the 1.5-mg/kg cohort. Two days of BL-8040 monotherapy triggered the mobilization of blasts into peripheral blood, with significantly higher mean fold-changes in responders versus nonresponders. This was accompanied by a decrease in bone marrow blasts.<br />Conclusions: The current results demonstrate the efficacy of CXCR4 targeting with BL-8040 and support continued clinical development in acute myelogenous leukemia.<br /> (© 2020 American Cancer Society.)
- Subjects :
- Adult
Aged
Antineoplastic Combined Chemotherapy Protocols adverse effects
Bone Marrow Cells drug effects
Drug Administration Schedule
Drug Resistance, Neoplasm
Female
Hematopoietic Stem Cell Mobilization
Humans
Leukemia, Myeloid, Acute blood
Leukemia, Myeloid, Acute mortality
Male
Middle Aged
Peptides adverse effects
Peptides pharmacokinetics
Recurrence
Remission Induction
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Cytarabine administration & dosage
Leukemia, Myeloid, Acute drug therapy
Peptides administration & dosage
Receptors, CXCR4 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0142
- Volume :
- 127
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 33270904
- Full Text :
- https://doi.org/10.1002/cncr.33338