Phase IIB Trial of Oral Midostaurin (PKC412), the FMS-Like Tyrosine Kinase 3 Receptor (FLT3) and Multi-Targeted Kinase Inhibitor, in Patients With Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome With Either Wild-Type or Mutated FLT3
Open accessAbstract
Purpose: Mutations leading to constitutive activation of the FMS-like tyrosine kinase 3 receptor (FLT3) occur in blasts of 30% of patients with acute myeloid leukemia (AML). Midostaurin (PKC412; N-benzoylstaurosporin) is a multitargeted tyrosine kinase inhibitor, with demonstrated activity in patients with AML/myelodysplastic syndrome (MDS) with FLT3 mutations. Patients and Methods: Ninety-five patients with AML or MDS with either wild-type (n = 60) or mutated (n = 35) FLT3 were randomly assigned to receive oral midostaurin at 50 or 100 mg twice daily. The drug was discontinued in the absence of response at 2 months, disease progression, or unacceptable toxicity. Response was defined as complete response, partial response (PR), hematologic improvement, or reduction in peripheral blood or bone marrow blasts by ≥ 50% (BR). Results: The rate of BR for the population in whom efficacy could be assessed (n = 92) was 71% in patients with FLT3-mutant and 42% in patients with FLT3 wild-type. One PR occurred in a patient with FLT3-mutant receiving the 100-mg dose regimen. Both doses were well-tolerated; there were no differences in toxicity or response rate according to the dose of midostaurin. Conclusion: These results suggest that midostaurin has hematologic activity in both patients with FLT3-mutant and wild-type. The degree of clinical activity observed supports additional studies that combine midostaurin and other agents such as chemotherapy especially in FLT3-mutant AML.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a newly diagnosed FLT3-mutated acute myeloid leukemia patient sample, midostaurin showed no significant change in mass accumulation rate distribution compared with a DMSO control.
“Cells in midostaurin showed no significant change in their distribution of MAR as compared to a DMSO control, consistent with the limited activity of single-agent midostaurin in FLT3-mutated AML27.”
From Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate (2016) · cites this paper as [27]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Cheson, B. D., Bennett, J. M., Kopecky, K. J., Büchner, T., Willman, C. L., Estey, E. H., Schiffer, C. A., Döhner, H., Tallman, M. S., Lister, T. A., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.036 · Cited by 2,686 · see citing works
Self-citationCreutzig, U., & Kaspers, G. J. L. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.99.116 · Cited by 2,137 · see citing works
Cheson, B. D., Bennett, J. M., Kantarjian, H. M., Pinto, A., Schiffer, C. A., Nimer, S. D., Löwenberg, B., Beran, M., de Witte, T. M., Stone, R. M., et al. (2000) · PubMed · Cited by 666 · see citing works
Self-citationStone, R. M., DeAngelo, D. J., Klimek, V. M., Galinsky, I. A., Estey, E. H., Nimer, S. D., Grandin, W. E., Lebwohl, D., Wang, Y., Cohen, P. S., et al. (2004) · Blood · doi:10.1182/blood-2004-03-0891 · Cited by 659 · see citing works
Self-citationWeisberg, E., Boulton, C. L., Kelly, L. M., Manley, P. W., Fabbro, D., Meyer, T., Gilliland, D. G., & Griffin, J. D. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00069-7 · Cited by 603 · see citing works
Self-citationBurnett, A. K., Goldstone, A. H., Stevens, R., Hann, I. M., Rees, J. K. H., Gray, R. G., & Wheatley, K. (1998) · The Lancet · doi:10.1016/s0140-6736(97)09214-3 · Cited by 560 · see citing works
Kelly, L. M., Liu, Q., Kutok, J. L., Williams, I. R., Boulton, C. L., & Gilliland, D. G. (2002) · Blood · doi:10.1182/blood.v99.1.310 · Cited by 487 · see citing works
Self-citationCT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML)
Kelly, L. M., Yu, J., Boulton, C. L., Apatira, M., Li, J., Sullivan, C. M., Williams, I. R., Amaral, S. M., Curley, D. P., Duclos, N., et al. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00070-3 · Cited by 305 · see citing works
Self-citationKäyser, S., Schlenk, R. F., Londoño, M. C., et al. (2009) · Blood · doi:10.1182/blood-2009-03-209999 · Cited by 272 · see citing works
Heidel, F. H., Solem, F. K., Breitenbuecher, F., Lipka, D. B., Kasper, S., Thiede, M., Brandts, C., Serve, H. L., Roesel, J. L., Giles, F. J., et al. (2005) · Blood · doi:10.1182/blood-2005-06-2469 · Cited by 270 · see citing works
Self-citationFLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML
Pratz, K. W., Sato, T., Murphy, K. M., et al. (2009) · Blood · doi:10.1182/blood-2009-09-242859 · Cited by 243 · see citing works
Phase I and Pharmacokinetic Study of PKC412, an Inhibitor of Protein Kinase C
PROPPER, D. J., McDonald, A. C., Man, A., Thavasu, P., Balkwill, F. R., Braybrooke, J. P., Caponigro, F., Gräf, P., Dutreix, C., Blackie, R., et al. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.5.1485 · Cited by 234 · see citing works
Self-citationLevis, M. J., Pham, R., Smith, B. D., & Small, D. (2004) · Blood · doi:10.1182/blood-2004-01-0388 · Cited by 215 · see citing works
Gilliland, D. G., & Griffin, J. D. (2002) · Current Opinion in Hematology · doi:10.1097/00062752-200207000-00003 · Cited by 201 · see citing works
Self-citationLevis, M. J., Brown, P. A., Smith, B. D., Stine, A., Pham, R., Stone, R. M., DeAngelo, D. J., Galinsky, I. A., Giles, F., Estey, E. H., et al. (2006) · Blood · doi:10.1182/blood-2006-04-015743 · Cited by 200 · see citing works
Self-citationBreitenbuecher, F., Schnittger, S., Grundler, R., Markova, B., Carius, B., Brecht, A., Duyster, J., Haferlach, T., Huber, C., & Fischer, T. H. (2008) · Blood · doi:10.1182/blood-2007-11-125476 · Cited by 138 · see citing works
Self-citationNew designs for phase 2 clinical trials
Estey, E. H., & Thall, P. F. (2003) · Blood · doi:10.1182/blood-2002-09-2937 · Cited by 113 · see citing works
Self-citationAn FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML
Bullinger, L., Döhner, K., Kranz, R., Stirner, C., Fröhling, S., Scholl, C., Kim, Y. H., Schlenk, R. F., Tibshirani, R. J., Döhner, H., et al. (2008) · Blood · doi:10.1182/blood-2007-09-115055 · Cited by 98 · see citing works
The Difficult Problem of Acute Myeloid Leukemia in the Older Adult
Stone, R. M. (2002) · CA A Cancer Journal for Clinicians · doi:10.3322/canjclin.52.6.363 · Cited by 97 · see citing works
Self-citationA Bayesian strategy for screening cancer treatments prior to phase II clinical evaluation.
Thall, P., & Estey, E. (1993) · Statistics in Medicine · doi:10.1002/sim.4780121303 · Cited by 42 · see citing works
Self-citationStone, R. M., Fischer, T., PAQUETTE, R. L., et al. (2009) · Blood · doi:10.1182/blood.v114.22.634.634 · Cited by 37 · see citing works
Self-citationNovel FLT3 tyrosine kinase inhibitors
Levis, M. J., & Small, D. (2003) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.12.12.1951 · Cited by 35 · see citing works
Yin, O. Q. P., Wang, Y., & SCHRAN, H. F. (2008) · Clinical Pharmacokinetics · doi:10.2165/0003088-200847120-00005 · Cited by 29 · see citing works
Yin, O. Q. P., Wang, Y., Lanza, C., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.7064 · Cited by 9 · see citing works
Self-citationDutreix, C., Labed, A. H., Roesel, J. L., Lanza, C., & Wang, Y. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.15_suppl.e14540 · Cited by 3 · see citing works
Self-citationClonal Abnormalities in MSC Derived from AML Bone Marrows
Andreeff, M., McQueen, T. J., Williams, C., Gu, J., Hopwood, V. L., Appleberry, T., Rich, C., Dallaire, S., Kornblau, S. M., & Wang, R. (2008) · Blood · doi:10.1182/blood.v112.11.2428.2428 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The target landscape of clinical kinase drugs
Klaeger, S., Heinzlmeir, S., Wilhelm, M., Polzer, H., Vick, B., Koenig, P.-A., Reinecke, M., Ruprecht, B., Petzoldt, S., Meng, C., et al. (2017) · Science · doi:10.1126/science.aan4368 · Cited by 854 · see citing works
An integrated approach to uncover drivers of cancer
Akavia, U. D., Litvin, O., Kim, J., Sanchez-Garcia, F., Kotliar, D., Causton, H. C., Pochanard, P., Mozes, E., Garraway, L. A., & Pe'er, D. (2010) · Cell · doi:10.1016/j.cell.2010.11.013 · Cited by 484 · see citing works
Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate
Stevens, M. M., Maire, C. L., Chou, N., Murakami, M. A., Knoff, D. S., Kikuchi, Y., Kimmerling, R. J., Liu, H., Haidar, S., Calistri, N. L., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3697 · Cited by 106 · see citing works
Seipel, K., Marques, M. A. T., Sidler, C., Mueller, B. U., & Pabst, T. (2018) · Haematologica · doi:10.3324/haematol.2018.191650 · Cited by 45 · see citing works
- Authors
- Fischer, T., Stone, R. M., DeAngelo, D. J., Galinsky, I., Estey, E., Lanza, C., Fox, E., Ehninger, G., Feldman, E. J., Schiller, G. J., Klimek, V. M., Nimer, S. D., Gilliland, D. G., Dutreix, C., Huntsman-Labed, A., Virkus, J., & Giles, F. J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2010-10-01
- Volume
- 28
- Issue
- 28
- Pages
- 4339-4345
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC4135183
- OpenAlex
- W2154625299
- Cited by
- 504
- References
- 26
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 20 · 2023: 31 · 2022: 35 · 2021: 35 · 2020: 44 · 2019: 44 · 2018: 29 · 2017: 48 · 2016: 21 · 2015: 41 · 2014: 45 · 2013: 30 · 2012: 36
- FWCI
- 17.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Celgene
- National Cancer Institute (P01CA066996)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Keywords
- midostaurin, FLT3 mutation, acute myeloid leukemia, myelodysplastic syndrome, tyrosine kinase inhibitors, hematologic response, dose comparison, drug toxicity, combination chemotherapy
- MeSH terms
- Administration, Oral, Aged, Antineoplastic Agents, Female, Humans, Male, Mutation, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Treatment Outcome, Staurosporine, Receptor Protein-Tyrosine Kinases, fms-Like Tyrosine Kinase 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
