Besponsa (inotuzumab ozogamicin)

P2, N=20, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P3, N=310, Suspended, Alliance for Clinical Trials in Oncology | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

Currently, most leukemias are effectively treated with immunotherapies (highly effective monoclonal antibodies targeting CD19 [blinatumomab], or CD22 [inotuzumab ozogamicin]), BCR::ABL1 tyrosine kinase inhibitors (TKIs; e.g., dasatinib, ponatinib), Bruton TKIs (e.g., ibrutinib, acalabrutinib), BCL-2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, olutasidenib, and enasidenib), FLT3 inhibitors (e.g., midostaurin, quizartinib, and gilteritinib), menin inhibitors (revumenib, ziftomenib), and chimeric antigen receptor T-cell therapies. Herein, we provide a high-level overview of prominent clinical developments across all leukemias. In contemporary times, harnessing the benefits of novel targeted therapies and the evolving treatment landscape bolster the optimistic view that most, if not all, leukemias are curable.

Despite recent advancements, patients with B-cell ALL tend to have poorer outcomes, especially in the adult population. Future research and larger scale prospective studies are indicated to evaluate the efficacy of InO in different lines of therapy.

P2/3, N=765, Not yet recruiting, Charite Universitaetsmedizin Berlin KR

P3, N=5951, Recruiting, Children's Oncology Group | Trial completion date: Mar 2030 --> Mar 2032 | Trial primary completion date: Mar 2030 --> Mar 2032

This review summarizes recent advances in the application of low-intensity chemotherapy, CD19/CD22-targeting antibodies such as blinatumomab and inotuzumab ozogamicin, the BCL-2 inhibitor venetoclax, and chimeric antigen receptor (CAR) T-cell therapy for elderly pH⁻ B-ALL patients. Clinical studies indicate that these strategies can increase remission rates and survival while reducing treatment-related toxicity, offering particular benefit to older patients who are unsuitable for intensive chemotherapy. Future efforts should focus on optimizing combination and sequential regimens, as well as personalizing treatment approaches to further improve efficacy and safety.

Targeted therapies, such as tyrosine kinase inhibitors for Philadelphia chromosome-positive ALL, Chimeric Antigen Receptor T cell therapy for relapsed or refractory cases, and monoclonal antibodies like blinatumomab and inotuzumab ozogamicin, have transformed treatment outcomes while reducing chemotherapy-related toxicity. Despite these advances, challenges remain, including the development of therapy resistance (e.g., BCR-ABL1 and FLT3 mutations) and long-term adverse effects such as cardiotoxicity and secondary malignancies. This narrative review summarizes recent innovations in risk assessment and targeted therapies, highlights current challenges, and discusses future directions to optimize personalized pediatric leukemia care.

P2, N=5, Terminated, St. Jude Children's Research Hospital | N=32 --> 5 | Trial completion date: Dec 2031 --> Sep 2025 | Recruiting --> Terminated | Trial primary completion date: Dec 2029 --> Sep 2025; Closed due to slow accrual

Although mAbs such as rituximab are primarily used in adults, the other modalities have demonstrated efficacy in both pediatric and adult patients with B-ALL. Among ADCs, inotuzumab ozogamicin (InO) has proven effective as monotherapy for relapsed disease, leading to FDA approval for patients aged >1 year with relapsed/refractory B-ALL...T-cell-engaging antibodies are now a standard component of therapy for most patients with newly diagnosed and relapsed B-ALL, following the successful integration of the bispecific T-cell-engager blinatumomab into chemotherapy regimens for both adults and children...Overall, immune-based therapies are now a mainstay of B-ALL therapy. This article reviews the efficacy and safety data of several immune-based therapies in B-ALL and discusses a number of outstanding questions and possible future directions for the use of immune-based approaches in the treatment of B-ALL.

Supportive care included epoetin alfa, romiplostim, iron, and vitamin supplementation. CONCLUSIONS This is the first known reported case that demonstrates the feasibility and effectiveness of a chemotherapy-free induction strategy using inotuzumab and blinatumomab for frontline treatment of Ph-negative B-ALL in Jehovah's Witness patients. It shows that MRD negativity can be safely achieved without cytotoxic chemotherapy or transfusion support and supports the use of the ALLIANCE A041703 trial regimen as a treatment model for this unique and underserved patient group.

P1, N=23, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial completion date: Jun 2026 --> Dec 2026