clofarabine

P3, N=727, Completed, ECOG-ACRIN Cancer Research Group | Active, not recruiting --> Completed

P1, N=4, Recruiting, Roberto Vargas | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

P2/3, N=745, Completed, Universitätsklinikum Hamburg-Eppendorf | Active, not recruiting --> Completed

P3, N=5949, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Oct 2025

Objective: To investigate the efficacy and prognosis of CLAG±DAC (Clofarabine, Cytarabine, G-CSF±Decitabine) chemotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) . The remission rate was relatively higher in patients with R/R AML combined with FLT3-ITD mutation by applying the DAC+CLAG regimen (OR=10.84, 95%CI 1.48-288.50, P=0.04) . The CLAG±DAC regimen is considered effective in patients with R/R AML, whereas decitabine combined with the CLAG regimen is more suitable for patients with R/R AML combined with FLT3-ITD mutation.

CD20+ tumors received rituximab. Gem/Clo/Bu patients had better median EFS (12 vs. 3 months, P = 0.001) and OS (25 vs. 7 months, P = 0.003) than 113 Flu/Mel matched-pair controls. The new myeloablative regimen Gem/Clo/Bu has limited toxicity and high activity in allo-SCT for aggressive lymphomas, yielding better outcomes than concurrent matched-pair controls receiving Flu/Mel.

P1, N=4, Recruiting, Omar Mian | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Dec 2024

P1, N=1, Terminated, Malika Kapadia | Phase classification: P1/2 --> P1 | N=28 --> 1 | Trial completion date: Dec 2028 --> Dec 2023 | Recruiting --> Terminated | Trial primary completion date: Dec 2027 --> Oct 2023; On 7/26/24 the Sponsor-Investigator was notified GlycoMimetics was terminating contracting for NCT05569512 following company restructuring. This notification came ahead of the study meeting criteria to progress from Phase 1 to Phase 2.

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

While our results call for PPP2R1A mutant and context-dependent effects upon clofarabine/nucleoside analogue monotherapy, combining clofarabine with a pharmacologic PP2A inhibitor proved synergistically in all tested conditions, highlighting a new generally applicable strategy to improve treatment outcome in USC.

Exposure of intestinal organoids to busulfan, fludarabine, and clofarabine induced damage-related responses affecting both the capacity to regenerate and transcriptional reprogramming. Increased levels of Gal-9 were found early after HSCT chemotherapeutic conditioning in the plasma of patients who later developed acute GVHD. Taken together, chemotherapy-induced intestinal damage can influence T cell behavior in a Gal-9-dependent manner which may provide novel strategies for therapeutic intervention.

P1/2, N=64, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Jun 2024 | Trial primary completion date: May 2025 --> Jun 2024

P1/2, N=64, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025

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

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.

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.

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.