P4, N=800, Active, not recruiting, The Cleveland Clinic | Recruiting --> Active, not recruiting

P4, N=219, Completed, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Active, not recruiting --> Completed | Trial completion date: Feb 2024 --> Sep 2023

Cladribine plus BuCy intensive conditioning regimen before allo-HSCT exhibits favorable treatment efficacy with acceptable toxicity in R/R AML patients.

Furthermore, we observed reduced T cell responses to autoantigens possibly presented by B cells (RASGRP2 and a-B crystallin (CRYAB)) at W52 and W96 and a further reduction in responses to the myelin antigens myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) after 96 weeks. We conclude that the effects of cladribine observed after year one are maintained and, for some effects, even increased two years after the initiation of a full course of treatment with cladribine tablets.

P2, N=40, Not yet recruiting, University of Colorado, Denver

P1, N=3, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P2, N=160, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

P2, N=160, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

P1, N=26, Active, not recruiting, Medical College of Wisconsin

P1, N=36, Not yet recruiting, Medical College of Wisconsin

P=N/A, N=116, Completed, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Active, not recruiting --> Completed

TPI1 is dramatically overexpressed in LSCC than in normal tissue, and the high expression of TPI1 may promote LSCC deterioration through its metabolic and non-metabolic functions. This study contributes to advancing our knowledge of LSCC pathogenesis and may have implications for the development of targeted therapies in the future.

P1, N=26, Active, not recruiting, Medical College of Wisconsin | Trial primary completion date: Oct 2024 --> May 2024

P2, N=237, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

Cladribine added to a backbone regimen of high dose cytarabine [≥ 1 gram per m2 intravenously (IV) for up to 5 days] and idarubicin (CLIA; further HD-clad) or low dose cytarabine [LDAC; 20 mg twice daily subcutaneously (SQ) for up to 10 days] alternating every two cycles with hypomethylating agent (HMA; regimen referred as LD-clad) have been routinely used in the treatment of AML at our institution. Cladribine added to chemotherapy is an effective approach in patients with AML from MPN, either as an induction therapy for those eligible for SCT or acceptable long-term therapy for non-eligible patients. Noticeably, almost 40% of patients without SCT were alive past 12 months since the initiation of LD-clad therapy. HMA pretreated patients had lower response rates and poor survival even in the frontline setting.

P=N/A, N=360, Recruiting, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Not yet recruiting --> Recruiting

Supported by Merck Healthcare KGaA

P1, N=40, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Feb 2024 --> Oct 2023

In summary, we showed the significance of selected ICI as outcome predictors in AML management. Further, multicentre studies are required for validation of those data.

Our real-world data on the effectiveness and safety of cladribine tablets are comparable to the pivotal study and other real-world data with no new safety signals.

HCL is an indolent chronic lymphoproliferative disorder and diagnosis is usually straightforward. However, atypical expression of CD5 renders its differential diagnosis more difficult, but FC is a useful tool that allows an optimal classification of the disease and allows initiation of timely satisfactory therapy.

CD 10+ HCL was the most prevalent atypical immunophenotypic subgroup. Bone marrow biopsy and flow cytometry are crucial diagnostic tools to rule out hairy cell leukemia. However, BRAF V600E mutation analysis should be performed in cases with unusual presentation or resistance to treatment.

CLAE regimen followed by allo-HSCT may be an effective salvage treatment option for R/R AL patients to prolong the overall survival.

In this work, we extended the UISS-MS disease layer by adding two new treatments, i.e., cladribine and ocrelizumab, to show that UISS-MS can be potentially used to predict the effects of any existing or newly designed treatment against multiple sclerosis. The obtained results mirror those of the clinical trials, demonstrating that UISS-MS can correctly simulate the mechanisms of action and outcomes of the treatments. The successful retrospective validation concurred to confirm that UISS-MS can be considered a digital twin solution to be used as a support system to inform clinical decisions and predict disease course and therapeutic response at a single patient level.

Together these investigations on T and B cell subsets suggest that cladribine treatment impairs the B-T cell crosstalk and reduces their ability to mediate pathogenic effector functions. This may result in specific reduction of autoreactivity to RASGRP2 which is expressed in B cells and brain tissue.

P2/3, N=210, Recruiting, University of Giessen | Trial primary completion date: Dec 2022 --> Dec 2025

P1, N=0, Withdrawn, Ayman H Qasrawi | N=15 --> 0 | Not yet recruiting --> Withdrawn

Cladribine is recommended as front-line regimen of cHCL patients with satisfactory efficacy and prognosis. Conversely, response and clinical outcome in HCL-v patients still need to be improved.

She received induction chemotherapy as per AAML1831 with daunorubicin, cytarabine, and gemtuzumab...She progressed through three additional salvage regimens including decitabine-CLAG (cladribine, cytarabine), TVTC (topotecan, vinorelbine, thiotepa, clofarabine), and venetoclax/azacitidine... Pure erythroid leukemia is an essentially fatal AML subtype often delayed in diagnosis due to its complex morphology and inherent refractoriness to standard AML therapies. More research is needed to understand the disease's pathophysiology and incorporate novel therapies.

Clofarabine and cladribine are two FDA approved drugs that are administered for their inhibitory acts on DNA synthesis to treat relapsed or refractory acute lymphoblastic and myeloid leukemia. Among 26 new derivatives, we identified two compounds, BK50164 and BK60106, that cause cell death specifically in ES primarily due to inhibition of CD99 but not via inhibition of DNA synthesis. These findings provide a road map for the future development selective CD99 inhibitors for targeted treatment of ES.

In conclusion, cladribine is effective in 1L and 2L treatment of AdvSM. Mast cell leukemia, eosinophilia, application of < 3 cycles and a lack of response are adverse prognostic markers.

P2, N=8, Completed, Goethe University | N=25 --> 8

Moreover, this new regimen showed efficient MRD clearance early after allo-HSCT. The combined decitabine- and cladribine-based conditioning regimen showed a low relapse rate and a high survival without an increased incidence of GVHD or adverse effects and thus has potential for use in allo-HSCT for R/R AML, high-risk AML, and high-risk MDS.

P2, N=98, Not yet recruiting, University of Florida

Our results demonstrated the synergistic effect of Chidamide with Cladribine on cell growth arrest, cell cycle arrest, and apoptosis in AML and primary cells with genetic defects by targeting HDAC2/c-Myc/RCC1 signaling in AML. Our data provide experimental evidence for the undergoing clinical trial (Clinical Trial ID: NCT05330364) of Chidamide plus Cladribine as a new potential regimen in AML.

The conditioning regimen of 8 patients was without Cy nor idarubicin to reducing adverse cardiac reaction: the regimen of Bu + CLAD+ Ara-c for 6 patients; and the regimen of Bu + melphalan + CLAD + Ara-c for the other 2 patients. The estimated 2-year survival, relapse, and Leukemia-free survival rates were 94.1 ± 5.7%, 14.7 ± 7.9% and 85.3 ± 7.9%, respectively. A CLAD-combination conditioning regimen is efficient and safe for auto-HSCT, indicating an effective approach for AML treatment.

Background: Nucleotide metabolism has been exploited for over a decade in the treatment of MS as exemplified by the success of teriflunomide and cladribine. Targeting dCK with first-in-class inhibitor TRE-515 blocks symptoms across multiple EAE mouse models by specifically limiting activated B and CD4 T cell proliferation. TRE-515 has been well tolerated in dose escalation Phase I clinical trials. TRE-515 could represent a new once a day oral treatment drug class for relapsing forms of MS with strong efficacy and predicable safety.

P1/2, N=80, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023