About Bolder Science

Our mission is to provide healthcare professionals with unbiased clinical research information, easily.

Currently, you can access the following clinical trials being conducted worldwide:

339,504 studies
in
214 countries
Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/01/2020.
This website is for US healthcare professionals

Log In to Bolder Science

or

Don't have an account? Sign Up

Please enter your email address.

You will receive a link to create a new password via email.

Log In

Create an Account

or
(optional) ?

Welcome, !

Please complete the following 4 questions to ensure you receive the information that best suits your needs.

Clinical Trials of Interest

When I’m looking for information on clinical trials, I usually am interested in...

finding clinical trials in which to enroll my patients

Rarely Often

finding newly launched clinical trials (for all phases)

Rarely Often

updates on status changes for clinical trials

Rarely Often

pipeline molecules

Rarely Often

Drug Interventions

Enter up to 3 drug interventions you are currently interested in:

Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/01/2020.
Our Science
  • Lenalidomide (IMiD® Agent)

    The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

    Proposed Mechanism of Action

    Lenalidomide is an oral, small-molecule immunomodulatory agent that directly induces tumor-cell killing and enhances immune function in preclinical studies.1,2

    Lymphoma

    Lenalidomide co-opts cereblon, a component of the E3 ubiquitin ligase complex, leading to direct tumoricidal and immunomodulatory effects.3-6 Preclinical studies have demonstrated increased activity of lenalidomide in combination with rituximab, an anti-CD20 monoclonal antibody that has been leveraged in the treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia.7-12 Combinations of lenalidomide and rituximab are being investigated for the treatment of NHL subtypes, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma.13-15

    Myelodysplastic Syndromes

    Haploinsufficiency, caused when only 1 copy of a gene is present, is hypothesized to drive pathogenesis of del(5q) myelodysplastic syndromes (MDS)16-18 and may underlie the specific activity of lenalidomide.19 In myeloid cell lines, haploinsufficiency increases the sensitivity of del5q MDS cells to lenalidomide-mediated degradation of casein kinase 1A1 (CSNK1A1), a gene located in the deleted region of chromosome 5 in del(5q) MDS.20,21

    Preclinical and correlative studies in MDS cells suggest that in non-del(5q) MDS, the effects of lenalidomide on cellular progenitors and the microenvironment work together to promote normal erythropoiesis through expansion of progenitor populations,1,22 reduction in proinflammatory cytokines,22 and reduction of marrow microvessel density.22

    Multiple Myeloma

    In preclinical studies, lenalidomide has demonstrated direct tumoricidal and immunomodulatory effects, which are mediated in both myeloma and immune cells by co-opting cereblon, a component of the E3 ubiquitin ligase complex.2-6 This interaction triggers proteasome degredation of transcription factors Ikaros and Aiolos, resulting in downregulation of myeloma survival signals, IRF4 and c-Myc, and upregulation of immunoregulatory molecule IL-2.4,6,23

    Lenalidomide Hypothesized Mechanism of Action in Multiple Myeloma

    Lenalidomide is an IMiD agent shown in vitro to have direct tumoricidal and immunomodulatory effects in lymphoma, multiple myeloma, and myelodysplastic syndromes.

    Lenalidomide by Disease State

    Lenalidomide in Lymphoma

    Post Approval Research
    Mantle cell lymphoma: Relapsed/refractory

    Phase 3
    Diffuse large B-cell lymphoma (ABC-subtype): First-line

    Phase 3
    Follicular/marginal zone lymphoma: Relapsed/refractory

    View Trials Investigating Lenalidomide in Lymphoma
    View Rationale for Clinical Development

    Lenalidomide in Multiple Myeloma

    Post Approval Research
    Relapsed/refractory

    Post Approval Research
    Newly diagnosed

    Post Approval Research
    Maintenance

    View Trials Investigating Lenalidomide in Multiple Myeloma
    View Rationale for Clinical Development

    Rationale for Clinical Development

    Lenalidomide has shown direct anti-myeloma activity and direct stimulation of immune function in preclinical studies.2 Additional preclinical studies demonstrated increased anti-myeloma activity of lenalidomide in combination with dexamethasone and certain proteasome inhibitors and monoclonal antibodies.30-33 Celgene is currently investigating lenalidomide as a foundation for combination with other agents in multiple myeloma.

    View Related Pathways

    References

    1. Komrokji RS, List AF. Semin Oncol. 2011;38:648-657. PMID: 21943671
    2. Borello I. Leuk Res. 2012;36:S3-S12. PMID: 23176722
    3. Revlimid (lenalidomide) capsules, for oral use [package insert]. Summit, NJ: Celgene Corporation; 2019.
    4. Lu G, et al. Science. 2014;343:305-309. PMID: 24292623
    5. Lopez-Girona A, et al. Leukemia. 2012;26:2326-2335. PMID: 22552008
    6. Bjorklund CC, et al. Blood Cancer J. 2015;5:e354. PMID: 26430725
    7. Lagrue K, et al. Blood. 2015;126:50-60. PMID: 26002964
    8. Gribben JG, et al. J Clin Oncol. 2015;33:2803-2811. PMID: 26195701
    9. Ramsay AG, et al. Blood. 2009;114:4713-4720. PMID: 19786615
    10. Reddy N, et al. Br J Haematol. 2008;140:36-46. PMID: 17995965
    11. Zhang L, et al. Am J Hematol. 2009;84:553-559. PMID: 19565649
    12. Rituxan (rituximab) [package insert]. South San Francisco, CA: Genentech, Inc; 2016.
    13. ClinicalTrials.gov. https://clinicaltrials.gov/show/NCT01996865.
    14. ClinicalTrials.gov. https://clinicaltrials.gov/show/NCT01938001.
    15. ClinicalTrials.gov. https://clinicaltrials.gov/show/NCT02285062.
    16. Boultwood J, et al. Blood. 2002;99:4638-4641. PMID: 12036901
    17. Horrigan SK, et al. Blood. 1996;88:2665-2670. PMID: 8839861
    18. Ebert BL, et al. Nature. 2008;451:335-339. PMID: 18202658
    19. Wei S, et al. Proc Natl Acad Sci U S A. 2009;106:12974-12979. PMID: 19470455
    20. Hollenbach P, et al. Blood. 2014;124 [abstract 3606].
    21. Fink EC, et al. Blood. 2014;124 [abstract 4].
    22. List AF, et al. Cancer Control. 2006;13(suppl):4-11. PMID: 17242661
    23. Krönke J, et al. Science. 2014;343:301-305. PMID: 24292625
    24. Rawal S, et al. Blood. 2012;120 [poster 2766].
    25. Haslett PAJ, et al. J Infect Dis. 2003;187:946-955. PMID: 12660941
    26. Zhang LH, et al. Br J Haematol. 2013;160:487-502. PMID: 23252516
    27. Yang Y, et al. Cancer Cell. 2012;21:723-737. PMID: 22698399
    28. Shaffer AL, et al. Clin Cancer Res. 2009;15:2954-2961. PMID: 19383829
    29. Qian Z, et al. Leuk Res. 2011;35:380-386. PMID: 21047686
    30. Gandhi AK, et al. Br J Haematol. 2014;164:811-821. PMID: 24328678
    31. Gandhi AK, et al. Curr Cancer Drug Targets. 2010;10:155-167. PMID: 20088798
    32. Chauhan D, et al. Blood. 2010;116:4906-4915. PMID: 20805366
    33. Das DS, et al. Br J Haematol. 2015;171:798-812. PMID: 26456076