A recently published phase II clinical trial demonstrated that inotuzumab ozogamicin (InO) is safe and effective as a single-agent therapy in treating children and adolescents with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). The study’s principal investigator, Maureen O’Brien, MD, MS, director of the Leukemia/Lymphoma Program at Cincinnati Children’s, is co-principal investigator for a second study that will evaluate InO’s effectiveness when combined with chemotherapy in treating newly diagnosed high-risk B-ALL. Both studies are sponsored by Children’s Oncology Group. 

InO is a CD22-targeting antibody-drug conjugate approved by the Food and Drug Administration for the treatment of adults with relapsed or refractory B-ALL. CD22 is a surface protein expressed on the leukemic blasts in about 95% of cases of B-ALL. InO is well tolerated in adults. The most common side effects are low blood counts and liver toxicity, specifically sinusoidal obstruction syndrome (SOS).

The phase II study of single-agent InO in relapse, published in the Journal of Clinical Oncology (March 20, 2022), included 48 heavily pretreated patients ages 1 to 21 years with CD22-positive relapsed/refractory B-ALL.

“The patients who participated in this trial had few available treatment options; many had received multiple intensive chemotherapy regimens and/or immunotherapies and had subsequently relapsed or did not respond,” says O’Brien. “InO as a single agent led to remission in 28 patients (58.3%), many of whom went on to receive subsequent curative therapy—either hematopoietic stem-cell transplantation (HSCT) or CAR-T (chimeric antigen receptor T cell) therapy.” Of the 21 patients undergoing HSCT after single-agent InO, six (28.6%) developed grade 3 SOS, which is a serious toxicity of the liver. The most significant risk factor for SOS among patients treated with InO is subsequent HSCT. O’Brien descibed this as a motivation for studying InO in newly diagnosed patients who are not planned to receive HSCT.

“InO is one of the most effective single-agent therapies available for B-ALL, but we have to figure out how to use it as safely as possible, ideally in patients who are planned to receive standard chemotherapy and not HSCT,” she explains.

The phase III study is enrolling patients now. The large, randomized trial will evaluate the effectiveness of adding two cycles of InO to the standard chemotherapy backbone compared to the chemotherapy backbone alone. Researchers expect to enroll about 3,700 patients ages 1 to 25 years at 213 cancer centers in the US, Canada, Australia and New Zealand over the next four years, including 2,084 randomized patients with B-ALL.

To learn more about the phase II and phase III studies, contact Maureen O’Brien.