SJALL23H: Combination Antigen-Directed Induction Therapy for Newly Diagnosed Patients With B-Cell Precursor Acute Lymphoblastic Leukemia and Lymphoma
This is a Phase II clinical trial testing the use of two antigen-directed therapies, inotuzumab and blinatumomab, as part of induction therapy for children and young adults with newly diagnosed B-cell precursor acute lymphoblastic leukemia and lymphoma. Primary Objective * To assess if the flow-cytometry assessed MRD-negative remission rate following an immunotherapy-based Induction in NCI-high risk patients without favorable genetic features is higher than the results of similar patients treated on AALL1131. Secondary Objectives * To compare flow-cytometry assessed MRD-negative rates at the end of Induction for patients treated with this therapy compared to similar patients treated on TOT17. * To compare the rate of significant toxicities in patients treated with this therapy to those treated with standard-risk therapy on TOT17. * To assess the event free and overall survival of patients treated with this therapy.
• Enrollment on INITIALL.
• Age 1-18.99 years at the time of enrollment on INITIALL.
• B-Acute lymphoblastic leukemia or lymphoblastic lymphoma.
• No prior chemotherapy excluding therapy given on or allowed by INITIALL.
• NCI high-risk (age 10 years or greater or presenting WBC count ≥50,000 cells/microL) or NCI standard-risk and a HR clinical feature as listed below:
‣ CNS3 disease (≥5 WBC/microL CSF with blasts present)
⁃ Testicular involvement of leukemia
⁃ Steroid pretreatment defined as \>24 hours of therapy in the 14 days prior to enrollment on INITIALL if a preceding WBC to define NCI risk is unavailable
• For lymphoblastic lymphoma, Stage 3-4 disease OR Stage 1-2 disease in patient ages ≥10 years OR HR clinical feature as defined above.
• Adequate liver function defined as:
‣ Total bilirubin ≤ 1.5x the upper limit of normal for age and alanine transaminase (ALT) ≤ 5x the upper limit of normal for age. Patients with an elevated total bilirubin due to hemolysis are eligible if they have a direct bilirubin \<1.5x the upper limit of normal.
• Adequate renal function defined as:
‣ Calculated glomerular filtration rate (GFR) ≥ 50 mL/min/1.73m\^2 using the Bedside Schwartz equation OR creatinine below or equal to the maximum defined below:
• Age: 1 to \<2 years; maximum serum creatinine (mg/dL): 0.6 (male and female)
∙ Age: 13 to \<16 years; maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
∙ Age: ≥16 years; maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
• Eligibility for inclusion post-induction requires meeting the first 4 Inclusion criteria above AND:
‣ Treatment on SJALL23H for Induction OR
⁃ Lymphoblastic lymphoma, initially treated on an SJALL protocol OR standard (non-protocol) therapy, without a complete response at the end of induction OR
⁃ NCI-SR ALL at diagnosis and treated with an SJALL protocol OR standard (non-protocol) therapy who have
• Slow response to therapy (≥0.1% MRD at end of induction for patients with hyperdiploid ALL or ≥0.01% MRD at end of induction for others with ALL) OR
∙ HR genetics as defined in the protocol.
∙ These patients may receive no more than 2 weeks of post-induction therapy and should be transitioned to SJALL23H post-induction as soon as the qualifying genetic or MRD result is available.