NCT06533748

Therapy for Newly Diagnosed Patients With B-Cell Precursor Acute Lymphoblastic Leukemia and Lymphoma

SJALL23H: Combination Antigen-Directed Induction Therapy for Newly Diagnosed Patients With B-Cell Precursor Acute Lymphoblastic Leukemia and Lymphoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 128 (estimated)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 1 Year – 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

This study utilizes a single arm phase II design. Treatment will consist of 3 main phases: Induction, early post induction \[including Consolidation, Blinatumomab 1, High-Dose Methotrexate, Reinduction, Interim, Reconsolidation, and Blinatumomab 2\], and Maintenance. Induction: * Induction includes 7 days of therapy on the INITIALL classification protocol (NCT06289673) as well as 5 further weeks of treatment on this trial. Treatment includes 15 days of oral (PO) or intravenous (IV) dexamethasone, 3 weekly doses of vincristine IV, and 2 doses of inotuzumab IV on Days 2 and 8. Patients will then receive blinatumomab IV from Days 9-36. Dasatinib PO will be added beginning on Day 12 for patients with an ABL-class fusion including patients with Ph+ ALL. These patients will also receive dasatinib in all subsequent cycles of therapy. Intrathecal (IT) MHA will be given. Patients will have a week without chemotherapy at the end of Induction, although patients with Induction failure (MRD ≥5% disease) will proceed directly to consolidation. Patients unable to receive inotuzumab by day 3 receive cyclophosphamide IV on days 3-4. Early Post Induction: * Consolidation will be given following completion of Remission Induction Therapy. Patients receive cyclophosphamide intravenous (IV), cytarabine IV, inotuzumab IV, intrathecal (IT) MHA, and dasatinib PO for patients with ABL-class fusion. Patients will have a week without chemotherapy at the end of Consolidation. * Blinatumomab 1 will be given with IT MHA for four weeks to all patients after recovery from Consolidation. * High-dose Methotrexate will be given IV every two weeks for four cycles. Patients will also receive an IT MHA with each of the 2 week cycles and will take oral mercaptopurine continuously if tolerated. * Reinduction will consist of dexamethasone for 7 days in the first and third week, 3 weekly doses of vincristine IV, 1 dose of daunorubicin IV, 1 dose of calaspargase IV, intrathecal (IT) MHA one dose, and dasatinib PO daily (for patients with ABL-class fusion). * Interim includes mercaptopurine po daily for 6 weeks, dexamethasone for 1 week (5 days), daunorubicin and vincristine IV on day 1 of weeks 2 and 5, calaspargase IV on day 1 of weeks 1 and 4, IT MHA on day 1 of week 4 and dasatinib po daily for 6 weeks (for patients with ABL-class fusion). Patients will have a week without chemotherapy at the end of Interim Therapy. Patients with Down syndrome will not receive daunorubicin during this phase. * Reconsolidation will repeat therapy given in Consolidation but replace the investigational inotuzumab with traditional mercaptopurine. * Blinatumomab 2 will be given for four weeks to patients without clonal IgH rearrangements, those with end of Induction MRD, those in whom next-generation based sequencing MRD is unavailable, patients who did not receive blinatumomab during induction, or patients with Down syndrome after Reconsolidation. Maintenance therapy follows Reconsolidation or Blinatumomab 2 (for those patients receiving this therapy) and includes 8 pulses of dexamethasone and vincristine given every 4 weeks, weekly methotrexate, daily mercaptopurine, intrathecal therapy, and dasatinib (for patients with ABL-class fusions). Maintenance therapy lasts a total of 80 weeks. Duration of therapy is approximately 2¼ years. Follow-up is recommended until the patient is in remission for 10 years and is at least 18 years old.

Conditions

• Acute Lymphoblastic Leukemia
• Lymphoblastic Lymphoma

Interventions

Type	Name	Description
DRUG	Dexamethasone	Given orally (PO) or intravenously (IV).
DRUG	Vincristine	Given IV.
DRUG	Inotuzumab	Given IV.
DRUG	Blinatumomab	Given IV.
DRUG	Dasatinib	Given PO.
PROCEDURE	IT MHA	Given Intrathecal (IT), Age adjusted.
DRUG	Cyclophosphamide	Given IV.
DRUG	Cytarabine	Given IV or IT.
DRUG	Methotrexate	Given IT, IV, PO or intramuscular (IM).
DRUG	6-Mercaptopurine	Given PO.
DRUG	Calaspargase	Given IV.
DRUG	Daunorubicin	Given IV.
DRUG	Thioguanine	Given PO (participants intolerant to mercaptopurine).

Timeline

• Start date: 2025-01-23
• Primary completion: 2028-05-01
• Completion: 2034-05-01
• First posted: 2024-08-01
• Last updated: 2026-02-12

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study