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

NCT ID: NCT06607419

Last Updated: 2024-09-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-21
• Study Completion Date: 2030-05-31

Brief Summary

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.

Conditions

B-Cell Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Blinatumomab

Patients in this group should receive Blinatumomab

Group Type: EXPERIMENTAL

Blinatumomab

Intervention Type: DRUG

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

Interventions

Blinatumomab

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

Intervention Type: DRUG

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%.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fujian Children's Hospital

UNKNOWN

Sponsor Role: collaborator

Zhangzhou Affiliated Hospital of Fujian Medical University

OTHER

Sponsor Role: collaborator

Guizhou Provincial People's Hospital

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Xiamen University

OTHER

Sponsor Role: collaborator

Dalian Women and Children's Medical Center

UNKNOWN

Sponsor Role: collaborator

The Third Xiangya Hospital of Central South University

OTHER

Sponsor Role: collaborator

Hunan Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Ningbo Women & Children's Hospital

OTHER

Sponsor Role: collaborator

Anhui Provincial Children's Hospital

OTHER

Sponsor Role: collaborator

Jiangxi Province Children's Hospital

OTHER

Sponsor Role: collaborator

Yuying Children's Hospital of Wenzhou Medical University

OTHER

Sponsor Role: collaborator

Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Shuhong Shen

Chair of hematology oncology department of SCMC

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Anhui Provincial Children's Hospital

Hefei, Anhui, China

Site Status: NOT_YET_RECRUITING

Fujian Children's Hospital

Fuzhou, Fujian, China

Site Status: NOT_YET_RECRUITING

Shanghai Children's Medical center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Ningbo Women and Children's Hospital

Ningbo, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Shuhong Shen, PhD/MD

Role: CONTACT

shenshuhong@scmc.com.cn

86-18930830638

Wenting Hu, MD

Role: CONTACT

huwenting@scmc.com.cn

13524836748

Facility Contacts

Hongjun Liu, MD

Role: primary

13515657759@126.com

13515657759

Hui Zhang, PhD/MD

Role: primary

zhanghui@scmc.com.cn

15821333007

Shuhong Shen, PhD/MD

Role: primary

shenshuhong@scmc.com.cn

86-21-38626161 ext. 82077

Wenting Hu, MD

Role: backup

huwenting@scmc.com.cn

13524836748

Binfei Hu, MD

Role: primary

hbfdkc@sina.com

13777028360

References

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.

Reference Type: BACKGROUND

PMID: 31679130 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12209608 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31876009 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29358182 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32564243 (View on PubMed)

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):836-847. doi: 10.1056/NEJMoa1609783.

Reference Type: BACKGROUND

PMID: 28249141 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31971321 (View on PubMed)

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;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.

Reference Type: BACKGROUND

PMID: 30592986 (View on PubMed)

Loffler A, Kufer P, Lutterbuse R, Zettl F, Daniel PT, Schwenkenbecher JM, Riethmuller G, Dorken B, Bargou RC. A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood. 2000 Mar 15;95(6):2098-103.

Reference Type: BACKGROUND

PMID: 10706880 (View on PubMed)

Ribera JM. Efficacy and safety of bispecific T-cell engager blinatumomab and the potential to improve leukemia-free survival in B-cell acute lymphoblastic leukemia. Expert Rev Hematol. 2017 Dec;10(12):1057-1067. doi: 10.1080/17474086.2017.1396890. Epub 2017 Nov 1.

Reference Type: BACKGROUND

PMID: 29082835 (View on PubMed)

von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, Bader P, O'Brien MM, Brethon B, Bhojwani D, Schlegel PG, Borkhardt A, Rheingold SR, Cooper TM, Zwaan CM, Barnette P, Messina C, Michel G, DuBois SG, Hu K, Zhu M, Whitlock JA, Gore L. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2016 Dec 20;34(36):4381-4389. doi: 10.1200/JCO.2016.67.3301. Epub 2016 Oct 31.

Reference Type: BACKGROUND

PMID: 27998223 (View on PubMed)

Wolf E, Hofmeister R, Kufer P, Schlereth B, Baeuerle PA. BiTEs: bispecific antibody constructs with unique anti-tumor activity. Drug Discov Today. 2005 Sep 15;10(18):1237-44. doi: 10.1016/S1359-6446(05)03554-3.

Reference Type: BACKGROUND

PMID: 16213416 (View on PubMed)

Zhou H, Yin Q, Jin J, Liu T, Cai Z, Jiang B, Li D, Sun Z, Li Y, He Y, Ma L, Gao S, Hu J, He A, Du X, Liu D, Zhang X, Ke X, Zhuang J, Han Y, Wang X, Chen Y, Gordon P, Yu D, Zugmaier G, Wang J. Efficacy and safety of blinatumomab in Chinese adults with Ph-negative relapsed/refractory B-cell precursor acute lymphoblastic leukemia: A multicenter open-label single-arm China registrational study. Hematology. 2022 Dec;27(1):917-927. doi: 10.1080/16078454.2022.2111992.

Reference Type: BACKGROUND

PMID: 36000952 (View on PubMed)

Zhu M, Wu B, Brandl C, Johnson J, Wolf A, Chow A, Doshi S. Blinatumomab, a Bispecific T-cell Engager (BiTE((R))) for CD-19 Targeted Cancer Immunotherapy: Clinical Pharmacology and Its Implications. Clin Pharmacokinet. 2016 Oct;55(10):1271-1288. doi: 10.1007/s40262-016-0405-4.

Reference Type: BACKGROUND

PMID: 27209293 (View on PubMed)

Hogan LE, Brown PA, Ji L, Xu X, Devidas M, Bhatla T, Borowitz MJ, Raetz EA, Carroll A, Heerema NA, Zugmaier G, Sharon E, Bernhardt MB, Terezakis SA, Gore L, Whitlock JA, Hunger SP, Loh ML. Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse. J Clin Oncol. 2023 Sep 1;41(25):4118-4129. doi: 10.1200/JCO.22.02200. Epub 2023 May 31.

Reference Type: BACKGROUND

PMID: 37257143 (View on PubMed)

Jabbour E, Short NJ, Senapati J, Jain N, Huang X, Daver N, DiNardo CD, Pemmaraju N, Wierda W, Garcia-Manero G, Montalban Bravo G, Sasaki K, Kadia TM, Khoury J, Wang SA, Haddad FG, Jacob J, Garris R, Ravandi F, Kantarjian HM. Mini-hyper-CVD plus inotuzumab ozogamicin, with or without blinatumomab, in the subgroup of older patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: long-term results of an open-label phase 2 trial. Lancet Haematol. 2023 Jun;10(6):e433-e444. doi: 10.1016/S2352-3026(23)00073-X. Epub 2023 May 12.

Reference Type: BACKGROUND

PMID: 37187201 (View on PubMed)

van der Sluis IM, de Lorenzo P, Kotecha RS, Attarbaschi A, Escherich G, Nysom K, Stary J, Ferster A, Brethon B, Locatelli F, Schrappe M, Scholte-van Houtem PE, Valsecchi MG, Pieters R. Blinatumomab Added to Chemotherapy in Infant Lymphoblastic Leukemia. N Engl J Med. 2023 Apr 27;388(17):1572-1581. doi: 10.1056/NEJMoa2214171.

Reference Type: BACKGROUND

PMID: 37099340 (View on PubMed)

Chen H, Gu M, Liang J, Song H, Zhang J, Xu W, Zhao F, Shen D, Shen H, Liao C, Tang Y, Xu X. Minimal residual disease detection by next-generation sequencing of different immunoglobulin gene rearrangements in pediatric B-ALL. Nat Commun. 2023 Nov 17;14(1):7468. doi: 10.1038/s41467-023-43171-9.

Reference Type: BACKGROUND

PMID: 37978187 (View on PubMed)

Svaton M, Skotnicova A, Reznickova L, Rennerova A, Valova T, Kotrova M, van der Velden VHJ, Bruggemann M, Darzentas N, Langerak AW, Zuna J, Stary J, Trka J, Fronkova E. NGS better discriminates true MRD positivity for the risk stratification of childhood ALL treated on an MRD-based protocol. Blood. 2023 Feb 2;141(5):529-533. doi: 10.1182/blood.2022017003.

Reference Type: BACKGROUND

PMID: 36240445 (View on PubMed)

Jabbour EJ, Short NJ, Jain N, Jammal N, Jorgensen J, Wang S, Wang X, Ohanian M, Alvarado Y, Kadia T, Sasaki K, Garris R, Garcia-Manero G, Ravandi F, Kantarjian HM. Blinatumomab is associated with favorable outcomes in patients with B-cell lineage acute lymphoblastic leukemia and positive measurable residual disease at a threshold of 10-4 and higher. Am J Hematol. 2022 Sep;97(9):1135-1141. doi: 10.1002/ajh.26634. Epub 2022 Jun 24.

Reference Type: BACKGROUND

PMID: 35713551 (View on PubMed)

Other Identifiers

CBC-ALL2024-1

Identifier Type: -

Identifier Source: org_study_id