Campath (alemtuzumab)

P1, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026

P1/2, N=15, Recruiting, University of Illinois at Chicago | Trial primary completion date: Jan 2024 --> Jan 2025

However, increased infections and relapse resulted in a lack of survival benefit after long-term follow-up. ClinicalTrials.gov identifier: NCT00520130.

This study of ex vivo T-cell depleted SCT's demonstrates that NK cells recover quicker when compared to those receiving unfractionated grafts. These results may have implications for GvHD and the GvL effect which warrants further study.

P2, N=12, Recruiting, Children's National Research Institute

P2, N=53, Active, not recruiting, Northwestern University | Trial completion date: May 2023 --> May 2027

P1/2, N=130, Active, not recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Jan 2026

P2, N=75, Active, not recruiting, Children's Hospital of Philadelphia | Recruiting --> Active, not recruiting

P=N/A, N=25, Recruiting, Erasmus Medical Center | Not yet recruiting --> Recruiting

P2, N=25, Recruiting, Ohio State University Comprehensive Cancer Center | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=162, Recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial primary completion date: Dec 2024 --> Dec 2023

P2, N=40, Active, not recruiting, Boston Children's Hospital | Trial primary completion date: Jan 2024 --> Apr 2024

Abnormal cells in BM and PB became undetectable on microscopy and FCM, and the CNS lesion disappeared on MRI after second-line therapy with alemtuzumab...Allogeneic hematopoietic stem-cell transplantation was performed, and the fusion mRNA has now been undetectable for more than 5 years since transplantation. This is the first report of a T-PLL case with a CLEC16A::IL2 fusion gene.

P=N/A, N=30, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=50, Recruiting, Masonic Cancer Center, University of Minnesota | Trial primary completion date: Jul 2024 --> Jul 2025 | Trial completion date: Jul 2024 --> Jul 2026

P2, N=162, Recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

There is currently moderate- to very low-certainty evidence available regarding the benefits and harms of maintenance therapy in people with CLL. Anti-CD20 mAbs maintenance improved PFS, but also increased grade 3/4 AEs and all AEs. IMiD maintenance had a large effect on PFS, but also increased grade 3/4 AEs. However, none of the above-mentioned maintenance interventions show differences in OS between the maintenance and control groups. The effects of alemtuzumab maintenance are uncertain, coupled with a warning for drug-related infectious toxicity. We found no studies evaluating other novel maintenance interventions, such as B-cell receptor inhibitors, B-cell leukaemia-2/lymphoma-2 inhibitors, or obinutuzumab.

P1/2, N=72, Recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Not yet recruiting --> Recruiting

P2, N=22, Completed, Randy Windreich | Active, not recruiting --> Completed | Trial completion date: Nov 2023 --> Apr 2023 | Trial primary completion date: Nov 2023 --> Apr 2023

P2, N=30, Recruiting, Robert Nickel | Trial primary completion date: Dec 2024 --> Nov 2025

P1, N=18, Not yet recruiting, Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China

Approaches to prevent GVHD include pharmacologic strategies such as calcineurin inhibitors (cyclosporine, tacrolimus) combined with methotrexate or mTOR inhibitors (sirolimus), and IMP dehydrogenase inhibitors (mycophenolate mofetil). Increasingly, posttransplant cyclophosphamide is emerging as a promising strategy for GVCHD prevention especially in a setting of reduced intensity conditioning. Other approaches include serotherapy (ATG, Campath) and graft manipulation strategies...Targeted therapies including Bruton's tyrosine kinase inhibition, JAK1/2 inhibition, and ROCK2 inhibitors have improved cGVHD therapy, especially in the steroid refractory setting. Continued improvement in prophylactic strategies for cGVHD, identification of accurate cGVHD treatment endpoints, and access to novel therapeutic agents are expected to improve cGVHD outcomes.

Conditioning was myeloablative busulfan with pharmacokinetic monitoring and fludarabine +/- cyclophosphamide/thiotepa or a reduced intensity melphalan-based regimen with fludarabine. All patients received serotherapy with ATG or alemtuzumab. Post-PSCT immune suppression was none or mycophenolate mofetil (MMF) and/or a calcineurin inhibitor (CNI)... 41 patients with a variety of IEIs were included (Figure 1). At a median follow-up of 2.5 years, OS was 85% (95% CI 75-97%) and EFS 80% (95% CI 69-94%), but was variable by underlying disease (Figure 2). Three patients experienced graft failure (7.3%), two requiring a second transplant and one receiving donor lymphocyte infusion only.

P2, N=12, Recruiting, University of Calgary | Trial completion date: Jul 2024 --> Jul 2028 | Trial primary completion date: Jul 2023 --> Jul 2028

26) vs standard of care in lenalidomide-refractory patients with multiple myeloma and 1-3 prior lines of therapy...The patient received CHOEP-21 (cyclophosphamide-doxorubicin-vincristine-prednisone-etoposide) and achieved metabolic CR but relapsed soon after treatment was stopped. Subsequent treatment with gemcitabine-dexamethasone-cisplatin-alemtuzumab was followed by consolidation with fludarabine plus melphalan and matched allogeneic stem cell transplant... To our knowledge, this is the first case of CAR+ TCL occurring after infusion of a CAR-T therapy produced via lentiviral transduction (cilta-cel). This rare malignancy was potentially driven by genetic mutations (e. g.

MethodA randomized controlled phase 2 trial was conducted in patients with hematological malignancies after HLA-identical sibling alloSCT with alemtuzumab added to the graft...Front Immunol, 2018) However, most patients did not convert to FD in the T-cell compartment, suggesting the GvL-effect of CD4+ DLI was limited. We considered this GvL-effect insufficient to prevent relapse and stress the importance of CD8+ donor T cells as main drivers of alloreactivity after DLI following HLA-identical alloSCT.

Introduction: T-Cell Prolymphocytic Leukemia (T-PLL) is a rare, aggressive T-cell malignancy with very poor prognosis. No substantial differences in T-PLL response rates or survival were observed when using the TPLL-ISG criteria when compared to historical reports. Patients who had a CR or CRi to alemtuzumab that proceeded with allo-SCT had a significantly prolonged OS and PFS. Patients with CD4-CD8+ T-PLL had inferior survival , but this will need to be validated in a larger sample set.

HLH diagnosis was established, and patient was started on HLH-94 protocol with etoposide and dexamethasone. Immunosuppressive therapies with steroids, and etoposide are the conventional first-line agents based on the HLH94 protocol; however, refractory cases have been shown to respond to other immunosuppressive agents and biologics including ruxolitinib, alemtuzumab, and emapalumab. Figure 1: A. Hemophagocytosis (Macrophage ingesting lymphocyte) B. Hemophagocytosis, more specifically-erythrophagocytosis (macrophage ingesting red blood cell).

Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.

P1/2, N=23, Active, not recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Sep 2023 --> Sep 2026

P1/2, N=72, Not yet recruiting, National Heart, Lung, and Blood Institute (NHLBI)

Treatment is still ongoing for one of them, while the other one relapsed after 10 cycles and was subsequently treated with Alemtuzumab and then with Pembrolizumab. Regarding MF patients, 2 of them are still under treatment, while the other 2 had a disease progression after the 2nd and 3rd cycle, and respectively received RT palliation and Brentuximab...In our small but with a quite long follow-up case series, we confirm the hypothesis that patients with SS may achieve a longer response than MF ones, since mogamulizumab was employed for a mean number of 14 cycles in SS against 4 cycles in MF. In conclusion, mogamulizumab represents a valuable therapy for advanced SS/MF as it can produce prolonged responses in pluryrefractory patients.

P1/2, N=18, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Phase classification: P2 --> P1/2

Ruxolitinib, a JAK2 inhibitor, provided a promising therapeutic effect in a phase II study...Anti-CD52 antibody, alemtuzumab, or anti-IL-5 antibody, mepolizumab, are promising drugs to control symptoms that are associated with hypereosinophilic syndrome. Allo-SCT is anticipated as a curative treatment for CEL, but the evidence of Allo-SCT for CEL is still limited. Further study is required to define the treatment strategy.

Other first-line treatments and their corresponding median duration of response (months) included cyclosporine (n=7, 72 months), cyclophosphamide (n=5, 72 months), IVIG (n=1, 16 months), and methotrexate (n=11, 21 months). Subsequent lines of therapy included campath (n=9), cyclosporine (CSA) (n=4), cyclophosphamide (n=9), intravenous immunoglobulin (IVIG) (n=2), MTX (n=4), rituximab (n=1), sirolimus (n=1), tacrolimus (n=2), and tofacitinib (n=2)...These significant findings contribute substantially to advancing our comprehension of LGLL-associated HA and its optimal management strategies. AIHA in patients with LGLL points towards a global immune dysfunction in this disease beyond clonal cytotoxic T/NK cell expansion.

The fludarabine, cyclophosphamide, and alemtuzumab (FCA) LD regimen was also shown to extend host lymphocyte suppression and improve UCART22 expansion versus fludarabine and cyclophosphamide (FC) alone (Boissel N, et al...Cytokine release syndrome (CRS) occurred in 2/3 (67%) pts, with one G1 that resolved without treatment and one G2 that resolved after tocilizumab x1...Pt 3 was refractory to treatment, however this pt received bridging therapy with dasatinib for his ABL2 fusion, and on Day -1, only 47% of the leukemic cells expressed CD22 (down from 88% at screening)... As of 01 July 2023, 3 pts were enrolled into the first UCART22 P2 cohort at DL2. Pt 1 is a 17yo female with B-ALL with a hypodiploid karyotype and a germline TP53 mutation whose disease had previously failed to respond to multiagent chemotherapy, blinatumomab (blina), inotuzumab (ino), venetoclax (ven), allogeneic hematopoietic stem cell transplantation (HSCT), and autologous CD19 CAR T-cell therapy (CAR19) x2. Pt 2 is a 68yo female with Ph-negative B-ALL who relapsed with CD19-low disease after multiagent chemotherapy, ino, and blina.

Early SMN occurred in 3.2% of participants by 5-years post-HCT and was associated with cGVHD occurrence (HR=2.14, 95% CI 1.06-4.33) and older age (>18 v <9 years, HR=6.35, 95% CI 2.66-15.14), but not ex-vivo depletion or use of ATG or alemtuzumab...Use of CD34 selection or T-cell depletion may reduce the risk of GVHD in transplant FA patients, but does not appear to impact 5-yr OS. Risk for early SMN development in FA patients receiving HCT associates with older age and cGVHD.

Pts with RT occurring as large B-cell lymphoma who did not previously receive CIT (e.g., fludarabine, cyclophosphamide, bendamustine, chlorambucil) for their CLL/SLL were included...The remaining 14% had been treated with an anti-CD20 monoclonal antibody (MoAb), steroids, lenalidomide, radiation, or alemtuzumab... This is the largest cohort of pts who developed RT having received only SMI with no CIT for their CLL reported, thus reflecting the current treatment landscape. Despite being CIT-naïve, pts in our series who received tx for their CLL/SLL and then developed RT had a short OS, underscoring the need to develop better therapies for these pts. In contrast, as in other published analyses (Wang Haematologica 2020), pts w/o prior tx for CLL/SLL had more favorable outcomes, with a median OS of approximately 5 years.

TALEN® gene editing technology is used to inactivate the TRAC and CD52 genes to minimize graft-versus-host disease (GvHD) and allow for the use of alemtuzumab (CLLS52, an anti-CD52 monoclonal antibody) in the lymphodepletion (LD) regimen, respectively...After LD with FCA (fludarabine 30 mg/m2 × 3d, cyclophosphamide 0.5g/m2 × 3d, CLLS52 12 mg on D1, 24 mg on D2, D3), a single infusion of UCART20x22 is administered at a flat dose level ([DL1] 50 x 106 cells; [DL2] 150 x 106 cells; and [DL3] 450 x 106 cells)...Pt 3 is an 18yo female with R/R DLBCL transformed from marginal zone lymphoma who previously received chemoimmunotherapy, venetoclax, ibrutinib, BR, CAR19, obinutuzumab, glofitamab, tafasitamab, lenalidomide, and an experimental epigenetic modifier...Pt 1 had G1 CRS and received tocilizumab (toci) x3 and dexamethasone (dex) x1... As of 01 July 2023, 3 pts were enrolled and treated at DL1. Pt 1 is a 76yo female with double-expressor diffuse large B-cell lymphoma (DLBCL) relapsed after R-CHOP, radiation therapy, and polatuzumab vedotin with bendamustine/rituximab (BR) and was considered ineligible for CAR19 due to recent high dose bendamustine. Pt 2 is a 65yo female with R/R triple-hit lymphoma transformed from follicular lymphoma who was previously treated with radiation therapy, BR, dose-adjusted R-EPOCH, and two separate CAR19 treatments.

The therapies received in the first line after BTKi and BCL2i were allogeneic HSCT (4 patients), duvelisib (3 patients), oral CDK9i (2 patients), and 1 patient each with CAR-T, anti-CD20 bispecific antibody, alemtuzumab, vecabrutinib, zanubrutinib; and for patients with RT: venetoclax plus rituximab with anthracycline chemotherapy (2 patients), PI3Ki/PD-1 (1 patient), duvelisib (1 patient) (Figure 1). Patients with CLL/SLL who were failed by BTKi and BCL2i treatment have poor prognosis. Overall response rates to treatment immediately after BTKi and BCL2i treatment are low among doubly refractory patients. More effective treatments are needed to address the unmet therapeutic needs of CLL/SLL patients who are refractory to both BTKi and BCL2i.

P1/2, N=55, Active, not recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Recruiting --> Active, not recruiting | N=98 --> 55 | Trial primary completion date: Sep 2025 --> Jul 2023