clofarabine

P2, N=82, Not yet recruiting, Nantes University Hospital | N=60 --> 82

P2, N=72, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

P2, N=9, Terminated, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2024 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2024 --> Mar 2024; Low accrual

Methionine metabolism and polyamine synthesis can be attractive therapeutic targets in leukemia.

P1/2, N=12, Recruiting, ExCellThera inc. | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2023 --> Jun 2026

P1, N=18, Completed, Therapeutic Advances in Childhood Leukemia Consortium | N=36 --> 18

P2, N=60, Not yet recruiting, Nantes University Hospital

P2, N=11, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed

P2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=30 --> 0 | Not yet recruiting --> Withdrawn

P1, N=4, Recruiting, Omar Mian

P1, N=75, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

A similar synergism was observed in patient-derived cell samples. These findings will be important in designing clinical trials using these drug combinations as pre-transplant conditioning regimens for AML patients.

P2, N=31, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2023 --> Dec 2025

High CLIC1 expression samples were more sensitive to camptothecin, cisplatin, doxorubicin, erlotinib, paclitaxel, rapamycin, clofarabine, tanespimycin, methotrexate, everolimus, TAK-733, trametinib and AZD8330. Single-cell analysis unveiled that CLIC1 was expressed ubiquitously in tumor cells and tumor microenvironment. Overall, CLIC1 was a promising treatment vulnerability in glioma.

P1, N=29, Completed, Beth Israel Deaconess Medical Center | Active, not recruiting --> Completed

P2, N=302, Recruiting, Nantes University Hospital | Not yet recruiting --> Recruiting | Phase classification: P3 --> P2

P1, N=4, Recruiting, Omar Mian | Active, not recruiting --> Recruiting

Salvage therapies for patients included re-induction with 7+3, FLAG-Ida, mitoxantrone-containing regimens, clofarabine-based protocols, or combination of hypomethylating agents with venetoclax. In summary, de novo AML inv(3)/t(3; 3) is a rare and aggressive subtype of AML conferring extremely poor prognosis. There appears to be an increase of incidence in females affecting a slightly younger demographic. Consistent with previous studies, the presence of chr 7 abnormalities was associated with even worse outcomes, which interestingly also drive EVI1 overexpression.

Background: Bisantrene (Bis), is a topoisomerase-II inhibitor with anthracycline-like activity, lower cardiotoxicity, and activity in patients (pts) with relapsed (rel)/primary refractory (PR) acute myeloid leukemia (AML) (Am J Hematol, 2021). In this Phase II study in a very advanced group of relapsed refractory AML pts resistant to multiple previous lines of chemotherapy including transplantation and with a median of 50% blasts at study initiation, Bis/Clo/Flu combination therapy was found to be safe and well tolerated without cardiac toxicity or tumor lysis syndrome. The maximum length of Bis/Clo/Flu administration was 4 days due to rapidly reversible liver toxicity, and transaminitis. As expected in this highly pretreated population, the infection rates were high.

Intensive treatment regimens included infusional cytarabine with either daunorubicin or idarubicin (7+3), liposomal cytarabine and daunorubicin (CPX-351), and mitoxantrone, etoposide and cytarabine (MEC). Nonintensive regimens included hypomethylating agents (decitabine or azacitidine) with or without venetoclax and clofarabine with low-dose subcutaneous cytarabine... In our cohort, TP53 mutant AML patients treated with intensive chemotherapy and transplant have superior outcomes to those who do not. Since this was a retrospective study, we cannot rule out the possibility that these results are confounded by providers favoring more intensive therapies for fitter patients. However, these data imply that TP53 mutant patients may benefit from more intensive therapy and suggests that future work to define optimal therapy regimens in this patient population may incorporate intensive strategies.

P3, N=5937, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Sep 2024

P1/2, N=12, Recruiting, ExCellThera inc. | Trial completion date: Jul 2025 --> Dec 2025 | Trial primary completion date: Jul 2023 --> Dec 2023

P2, N=9, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Jul 2023 --> Jul 2024

This systematic review highlighted that tisagenlecleucel is a much more expensive therapy than conventional alternatives. However, tisagenlecleucel performed well on the ICER, not exceeding $100 000/QALY. It was also found that the advanced therapy product was more effective than the conventional small molecule and biological drugs, in terms of life years and QALY gained.

P2, N=2, Terminated, Milton S. Hershey Medical Center | N=20 --> 2 | Trial completion date: Jun 2026 --> Nov 2022 | Recruiting --> Terminated | Trial primary completion date: Jun 2024 --> Aug 2022; terminated due to low accrual

Lymphodepleting chemotherapy (LD) has emerged as a key determinant of chimeric antigen receptor T cell (CAR) efficacy across pediatric/adult B cell malignancies. Clofarabine is a purine nucleoside analog with mechanistic overlap with fludarabine; however, toxicity is high in the upfront leukemia setting, and thus use as an LD pre-CAR should be pursued with caution. We review the experience using bendamustine and clofarabine to serve as a resource when considering LD regimens as an alternative to fludarabine for pediatric B-ALL.

P3, N=302, Not yet recruiting, Nantes University Hospital

Clofarabine (Clo) is an immunosuppressive purine analog that may have better anti-leukemic activity than fludarabine (Flu). The median PFS and OS were 66 and 68 months respectively. As a conclusion, Clo/TBI (4-8 Gy) as a conditioning regimen for allo-SCT in high-risk patients confers disease control with an acceptable toxicity profile.

P2/3, N=793, Active, not recruiting, St. Jude Children's Research Hospital | Recruiting --> Active, not recruiting

Trends to improved EFS with venetoclax and cladribine/clofarabine containing regimens were observed in My-AML and Mo-AML, respectively (Fig 1E-F). Our data support that disease transformation in CMML can occur through three distinctphenotypic trajectories characterized by specific genomic profiles and clonal evolution. This sets the basis for potential future studies to develop phenotype-specific targeted novel therapeutics.

P2, N=80, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2024 --> Apr 2027 | Trial primary completion date: Mar 2024 --> Oct 2026

Given the shortage of fludarabine, alternative preparative lymphodepleting regimens for CAR-T-cell therapy need to be identified. We present a case of relapsed/refractory B-cell acute lymphoblastic leukemia requiring multiple lines of salvage therapy with persistent extensive disease, who underwent lymphodepletion with clofarabine and cyclophosphamide before tisagenlecleucel CD19+ CAR-T-cell infusion with eventual remission. We offer evidence of clofarabine's activity against B-cell acute lymphoblastic leukemia in combination with tisagenlecleucel therapy. In this patient, clofarabine did not decrease CAR-T-cell effectiveness, supported by presence of cytokine release syndrome and ultimate minimal residual disease negativity both on flow cytometry and next-generation sequencing.

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.

P2, N=80, Recruiting, Fred Hutchinson Cancer Center | Not yet recruiting --> Recruiting

High CEP72 expression was a poor prognostic factor in patients diagnosed with multiple myeloma.

P1/2, N=12, Recruiting, ExCellThera inc. | Trial completion date: Apr 2024 --> Jul 2025 | Trial primary completion date: Apr 2023 --> Jul 2023

Little progress has been seen, where nelarabine is the only approved drug (overall response rate of 50%; associated hematologic/neurological toxicities)...Patient is currently 32 months post-transplant, continuing maintenance therapy, remains in CR.Patient 2: ETP-ALL (mutant NOTCH1/EZH2), received induction with hyperCVAD with persistent MRD (TCR-rearrangements), received re-induction with augmented-BFM/venetoclax, had undetectable TCR-rearrangements, received a haploidentical-HSCT (fludarabine/TBI-8Gy conditioning)...Last bone marrow evaluation showed CR but detectable TCR MRD, received two DLI doses complicated with liver GVHD responsive to systemic corticosteroids.Patient 4: Near-ETP ALL (normal karyotype-ASXL1/NOTCH1/TET2 mutations), received asparaginase-based treatment (GRAALL regimen), achieved CR with negative MRD, then completed two consolidation cycles, early-intensification followed by a matched-related allo-HSCT (clofarabine/TBI-8Gy conditioning)... Encouraging results presenting a foundation for further studies that could assess the efficacy of HMAs combined with BCL2 inhibitors not only in the post-transplant setting but also for high-risk T-ALL patients.