Table of Contents

• Clinical trial overview
• Conditions being studied
• Trial phases and study design
• Main endpoints and what they mean
• Who can take part
• Key trial summaries
• What these trials are trying to learn

Clinical trial overview

The trial data show that Alemtuzumab is being studied in several different research settings, not just one disease.^{[1][2][3][4][5]}

These studies are looking at people with multiple sclerosis, Langerhans Cell Histiocytosis, and relapsed or refractory blood cancers such as B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma.^{[1][2][3][4][5]}

The studies are all marked Authorised and use different trial phases, from early dose-finding work to later comparison studies.^{[1][2][3][4][5]}

Conditions being studied

One trial studies relapsed or refractory B-cell acute lymphoblastic leukemia, which means the leukemia came back or did not respond well to earlier treatment.^[1]

Another trial studies relapsed or refractory B-cell non-Hodgkin lymphoma, which is a group of cancers that start in B cells, a type of immune cell.^[4]

Two studies focus on multiple sclerosis, including aggressive relapsing remitting multiple sclerosis and relapsing remitting multiple sclerosis.^[3][5]

One large international protocol studies Langerhans Cell Histiocytosis in children and adolescents, including different forms such as multisystem disease, single-system disease, isolated CNS-risk lesions, and multifocal bone lesions.^[2]

Trial phases and study design

The studies include Phase 1/2, Phase 2, Phase 3, and Phase 4 trials.^{[1][2][3][4][5]}

Phase 1/2 studies are early trials that first check safety and dose, then begin to look at whether the treatment may help.^[1][4]

Phase 3 and Phase 4 studies are later-stage trials that compare treatment strategies and look at longer-term outcomes in larger groups.^[2][3][5]

One Phase 3 study in aggressive relapsing remitting multiple sclerosis compares HSCT (hematopoietic stem cell transplantation, a treatment that uses stem cells to rebuild the blood and immune system) with a comparator group that may include Alemtuzumab, cladribine, or ocrelizumab.^[3]

Main endpoints and what they mean

The leukemia and lymphoma studies mainly measure adverse events, serious adverse events, and dose-limiting toxicity, which are safety outcomes that show how well people tolerate the treatment.^[1][4]

These early studies also try to find the Maximum Tolerated Dose and the Recommended Phase 2 Dose for the cell therapy being tested.^[1][4]

The multiple sclerosis studies focus on NEDA, which stands for no evidence of disease activity, meaning there is no sign of active disease during the study period according to the trial rules.^[3][5]

The Langerhans Cell Histiocytosis study measures reactivation-free survival, overall survival, disease-free survival, the course of neurodegenerative CNS-LCH, response of isolated tumorous CNS lesions to 2-CdA, and the rate of permanent consequences.^[2]

In simple terms, these outcomes ask whether the disease stays quiet, comes back less often, or causes fewer long-term problems.^[2][3][5]

Who can take part

The target groups differ by trial, but they include adults with aggressive relapsing remitting multiple sclerosis, people with relapsed or refractory B-cell cancers, and children and adolescents with Langerhans Cell Histiocytosis.^{[1][2][3][4][5]}

Some studies are for people who have already tried other treatments, such as those who failed CD19-directed therapy in the B-cell acute lymphoblastic leukemia study.^[1]

Other studies include patients with risk organ involvement, non-risk organ involvement, or specific lesion types in Langerhans Cell Histiocytosis.^[2]

Key trial summaries

NCT04150497 is a Phase 1/2 study in relapsed or refractory B-cell acute lymphoblastic leukemia.^[1] It aims to assess safety and tolerability of UCART22 and to find the MTD and/or RP2D, with a dose-expansion part for patients who failed CD19-directed therapy.^[1]

NCT02205762 is a Phase 4 international protocol for children and adolescents with Langerhans Cell Histiocytosis.^[2] It studies reactivation-free survival, survival outcomes, neurodegenerative CNS-LCH, and long-term consequences.^[2]

NCT03477500 is a Phase 3 randomized study in aggressive relapsing remitting multiple sclerosis.^[3] It compares HSCT with a comparator group that may include Alemtuzumab, cladribine, or ocrelizumab and measures NEDA at 2 years and 5 years.^[3]

NCT05607420 is a Phase 1/2 study in relapsed or refractory B-cell non-Hodgkin lymphoma.^[4] It looks at safety, tolerability, dose-limiting toxicity, and dose selection for UCART20x22 in dose-finding and dose-expansion parts.^[4]

2024-515470-26-00 is a Phase 2 study in relapsing remitting multiple sclerosis.^[5] Its main endpoint is NEDA-3 over 36 months, which means the study checks whether there is any sign of MS disease activity during that time.^[5]

What these trials are trying to learn

Across the source data, the clinical trials involving Alemtuzumab are mainly trying to learn whether treatment strategies are safe, whether they control disease, and which patients benefit most.^{[1][2][3][4][5]}

In blood cancers, the focus is on safety and dose-finding, while in multiple sclerosis the focus is on disease activity over time.^[1][3][4][5]

In Langerhans Cell Histiocytosis, the studies aim to reduce reactivation and late effects while improving survival and long-term outcomes.^[2]