Efficacy Study of Blinatumomab Clean Up Early Residual Disease for Newly Diagnosed Pediatric B Lymphoblastic Leukemia

Overview

The goal of this clinical trial is to evaluate the efficacy of Blinatumomab in pediatric patient with newly diagnosed acute B-Lymphoblastic leukemia with poor response to early chemotherapy, i.e. day 19 MRD ≥ 0.1% (low-risk) or day 19 MRD ≥ 0.01% (intermediate-risk). The main question is: • If the flow cytometric MRD negative (\<0.01%) rate and the NGS- MRD negative (\<0.0001%) rate at the end of induction for patients received Blinatumomab will be superior to historical control (D46MRD in the CCCG-ALL2020 protocol). Participants will: * Take 14 days full dose Blinatumomab; * With bone marrow evaluated before and after Blinatumomab treatment.

Interventions

• Drug Blinatumomab
  Recruited patients will receive Blinatumomab since day 29 of induction for 14 days.

Primary outcome measures

• The flow cytometric MRD [Time frame: From the date of Blinatumomab completion to one week after its treatment course]
• The NGS- MRD [Time frame: From the date of Blinatumomab completion to one week after its treatment course]

Secondary outcome measures (3)

• 5-year EFS [Time frame: 5 years since the last recruited patient completed Blinatumomab.]
• Adverse events [Time frame: From day 19 of induction therapy until the start of the second high-dose methotrexate regimen.]
• Healthcare costs [Time frame: Six-month since window phase]

Eligibility criteria

Inclusion criteria

• Age older than 1 month to younger than 18 years.
• Diagnosis of acute lymphoblastic leukemia by bone marrow morphology.
• Immunophenotyping: acute B-lymphoblastic leukemia;
• Meet one of the following situations:

A. Provisional low-risk: D19MRD ≥ 0.1%; B. Provisional intermediate-risk: D19MRD ≥ 0.01%;

• Subjects in the sytudy group or their guardians must be able to understand and accept the informed consent approved by the Ethics Committee

Exclusion criteria

• sIgM+;
• ALL evolved from chronic myeloid leukemia (CML);
• Down's syndrome, or major congenital or hereditary disease with organ dysfunction;
• Other secondary leukemias;
• CNS involvement;
• History of epilepsy; or convulsions within the last month;
• Known underlying congenital immunodeficiency or metabolic disease;
• Congenital heart disease with cardiac insufficiency;
• Treated with glucocorticoids for ≥14 days, or ABL kinase inhibitors for > 7 days within one month before enrollment, or any chemotherapy or radiotherapy within 3 months before enrollment (except for emergency radiotherapy to relieve airway compression);
• Initial diagnosis of high risk;
• D46MRD ≥1%.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• Anhui Provincial Children's Hospital — Hefei
• Fujian Children's Hospital — Fuzhou
• Shanghai Children's Medical center — Shanghai
• Ningbo Women and Children's Hospital — Ningbo

Publications

• Clements JD, Zhu M, Kuchimanchi M, Terminello B, Doshi S. Population Pharmacokinetics of Blinatumomab in Pediatric and Adult Patients with Hematological Malignancies. Clin Pharmacokinet. 2020 Apr;59(4):463-474. doi: 10.1007/s40262-019-00823-8. PMID 31679130
• Dreier T, Lorenczewski G, Brandl C, Hoffmann P, Syring U, Hanakam F, Kufer P, Riethmuller G, Bargou R, Baeuerle PA. Extremely potent, rapid and costimulation-independent cytotoxic T-cell response against lymphoma cells catalyzed by a single-chain bispecific antibody. Int J Cancer. 2002 Aug 20;100(6):690-7. doi: 10.1002/ijc.10557. PMID 12209608
• Gokbuget N, Dombret H, Giebel S, Bruggemann M, Doubek M, Foa R, Hoelzer D, Kim C, Martinelli G, Parovichnikova E, Maria Ribera J, Schoonen M, Tuglus C, Zugmaier G, Bassan R. Blinatumomab vs historic standard-of-care treatment for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukaemia. Eur J Haematol. 2020 Apr;104(4):299-309. doi: 10.1111/ejh.13375. Epub 2020 Jan 24. PMID 31876009
• Gokbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Bruggemann M, Horst HA, Havelange V, Stieglmaier J, Wessels H, Haddad V, Benjamin JE, Zugmaier G, Nagorsen D, Bargou RC. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Apr 5;131(14):1522-1531. doi: 10.1182/blood-2017-08-798322. Epub 2018 Jan 22. PMID 29358182
• Horibe K, Morris JD, Tuglus CA, Dos Santos C, Kalabus J, Anderson A, Goto H, Ogawa C. A phase 1b study of blinatumomab in Japanese children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Int J Hematol. 2020 Aug;112(2):223-233. doi: 10.1007/s12185-020-02907-9. Epub 2020 Jun 20. PMID 32564243
• Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R, Arslan O, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Bruggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017 Mar 2;376(9):836-8 PMID 28249141
• Kiyoi H, Morris JD, Oh I, Maeda Y, Minami H, Miyamoto T, Sakura T, Iida H, Tuglus CA, Chen Y, Dos Santos C, Kalabus J, Anderson A, Hata T, Nakashima Y, Kobayashi Y. Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia. Cancer Sci. 2020 Apr;111(4):1314-1323. doi: 10.1111/cas.14322. Epub 2020 Feb 11. PMID 31971321
• Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;2 PMID 30592986

Identifiers

NCT: NCT06607419 · CBC-ALL2024-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗