Combination Chemotherapy With or Without Blinatumomab in Treating Patients With Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia

Summary

This randomized phase III trial studies combination chemotherapy with blinatumomab to see how well it works compared to induction chemotherapy alone in treating patients with newly diagnosed breakpoint cluster region (BCR)-c-abl oncogene 1, non-receptor tyrosine kinase (ABL)-negative B lineage acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether combination chemotherapy is more effective with or without blinatumomab in treating newly diagnosed acute lymphoblastic leukemia.

Timeline

Start

2014-05-19

Primary completion

2023-06-23

Completion

2027-02-25

Outcome

Met primary endpoint

registry analysis (superiority test); MRD Negative - Blinatumomab + Chemotherapy vs MRD Negative - Chemotherapy; p = 0.003; Hazard Ratio (HR) 0.44 (95% CI 0.25 to 0.76); Log Rank NCT02003222 ↗

paper The addition of blinatumomab to consolidation chemotherapy in adult patients in MRD-negative remission from BCP-ALL significantly improved overall survival. PMID 39047240 ↗

Publications

• Litzow MR, Sun Z, Mattison RJ, Paietta EM, Roberts KG, Zhang Y, Racevskis J, Lazarus HM, Rowe JM, Arber DA, Wieduwilt MJ, Liedtke M, Bergeron J, Wood BL, Zhao Y, Wu G, Chang TC, Zhang W, Pratz KW, Dinner SN, Frey N, Gore SD, Bhatnagar B, Atallah EL, Uy GL, Jeyakumar D, Lin TL, Willman CL, DeAngelo DJ, Patel SB, Elliott MA, Advani AS, Tzachanis D, Vachhani P, Bhave RR, Sharon E, Little RF, Erba HP, Stone RM, Luger SM, Mullighan CG, Tallman MS. Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults. N Engl J Med. 2024 Jul 25;391(4):320-333. doi: 10.1056/NEJMoa2312948.
• Seftel MD. Hyper-CVAD: a regimen for all seasons. Lancet Haematol. 2020 Jul;7(7):e501-e502. doi: 10.1016/S2352-3026(20)30179-4. No abstract available.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Blinatumomab	Monoclonal antibody	—	Intravenous
Background	Cyclophosphamide	Other / unclassified	—	Intravenous
Background	Cytarabine	Small molecule	—	Intrathecal
Background	Daunorubicin	Small molecule	—	Intravenous
Background	Dexamethasone	Small molecule	—	Oral
Background	Etoposide	Small molecule	—	Intravenous
Background	Leucovorin	Small molecule	—	Intravenous
Background	MERCAPTOPURINE ANHYDROUS	Small molecule	—	Oral
Background	Methotrexate	Small molecule	—	Intrathecal
Background	Pegaspargase	Protein / enzyme biologic	—	Intramuscular
Background	Prednisone	Other / unclassified	—	Oral
Background	Rituximab	Monoclonal antibody	—	Intravenous
Background	Vincristine	Small molecule	—	Intravenous

Indications