Pedi-cRIB: Overlapping Immunotherapy and Chemotherapy for Relapsed Leukemia

Summary:

Despite notable advances in bringing immunotherapy to pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), the most commonly used treatment regimen for relapsed disease (ALLR3) still results in the death of 2% of patients and a severe infection rate of 90%. Among responders, 38% still had detectable disease (MRD-positive).​ The less intensive regimen (AALL01P2) still has significant toxicity, 2.4% of patients die despite treatment, and 60% still have detectable disease at the end of the first cycle.​ If the induction cycle does put a patient in remission, the patient still needs a stem cell transplant (SCT) to consolidate the remission for their best chance of cure. The intensive chemotherapy and its associated toxicities can delay the much-needed SCT.​ Thus, a novel regimen is needed that both reduces chemotherapy to mitigate the toxicity of treatment allowing patients to go into remission and proceed with SCT without delay and utilizes targeted immunotherapy for increased efficacy.​ The integration of chemotherapy with targeted FDA-approved immunotherapies such as blinatumomab, rituximab, and inotuzumab has been proven effective in elderly patients with B-ALL and in relapsed/refractory adults with B-ALL. All three target crucial molecules on B-cells (CD19, CD20, and CD22, respectively). ​This approach is attractive because it is highly effective and has a lower toxicity. Additionally, it has been tested in six pediatric patients and all six were MRD-negative following the first cycle. Furthermore, none had serious infections during chemotherapy, four were able to immediately proceed to SCT, and three remain in remission more than year from SCT.​ This phase II study will evaluate the complete response rate of a chemotherapy backbone called mini-Hyper-CVD in combination with blinatumomab, rituximab, and inotuzumab in pediatric, adolescent, and young adults with relapsed or refractory B-ALL. This chemotherapy backbone has been found to be safe and improved efficacy when combined with immunotherapy.

Trial Registration: ClinicalTrials.gov Identifier: NCT05645718