Blinatumomab Plus Reduced-dose Chemotherapy in Treating B-ALL

Official title

Blinatumomab Combined With Reduced-dose Chemotherapy in Treating Precursor B Cell Acute Lymphoblastic Leukemia: a Phase II, Single Arm and Multicenter Study

Overview

Precursor B cell acute lymphoblastic leukemia (B-ALL) is an aggressive type of leukemia, with high relapse rate and poor long term survival in adults. Traditional treatment regimens mainly include chemotherapy and hematopoietic stem cell transplantation. In the past decade, with the application of molecular targeted drugs and immunotherapy, the survival of B-ALL patients has significantly improved. In this study，we propose a treatment approach that combines Blinatumomab and Reduced-dose Chemotherapy in B-ALL adults. Our study aims to answer the safety and efficacy of this treatment regimen, and further improve the survival for those participants.

Detailed description

This is a prospective, single-arm, phase II and open-label study. A total of 20 Ph-negative B-ALL participants will be enrolled. The primary endpoint is MRD-negative CR rate. The induction therapy is a combination of Blinatumomab(Blina), Vindesine(VDS), Cyclophosphamide(CTX) and Dexamethasone(DXM). The second cycle would be the combination of Blina and Venetoclax(VEN). As for consolidation therapy, we suggest the bone marrow transplantation. The purpose of this study is to explore the safety and efficacy of the treatment regimen in the treatment of newly diagnosed young Ph-negative B-ALL patients.

Interventions

• Drug Blinatumomab plus Reduced-dose Chemotherapy
  Cycle 1: Reduced VCP on day1, IV and Blinatumomab for 2 weeks, IV. Cycle 2: Blinatumomab for 2 weeks, IV and Venetoclax for 2 weeks, oral.

Primary outcome measures

• Complete remission rate with negative minimal residual disease [Time frame: at the end of cycle 1 and 2（each cycle is 28 days）]

Secondary outcome measures (4)

• CR/CRi after Cycle 1 and 2 [Time frame: at the end of cycle 1 and 2（each cycle is 28 days）]
• Minimal residual disease(MRD) [Time frame: At the end of each cycle（each cycle is 28 days）]
• Overall survival (OS) [Time frame: up to 5 years]
• Event free survival(EFS) [Time frame: up to 5 years]

Eligibility criteria

Inclusion criteria

• 1\. Before enrollment, patients must be diagnosed with de novo precursor B-cell acute lymphoblastic leukemia and be negative for Philadelphia chromosome. The diagnostic criteria refer to the 2022 WHO classification; 2. Age≥15 years， ≤59 years; 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; 4. Expected survival time ≥ 2 months; 5. No organ dysfunction that would restrict the use of this protocol during the screening period; 6. Understand the study and sign the informed consent form. 7. Men, women of childbearing age (only postmenopausal women who have been menopausal for at least 12 months can be considered infertile), and their partners voluntarily take effective contraceptive measures deemed effective by the investigator during the treatment period and for at least 12 months after the last dose of the study drug.

Exclusion criteria

• 1\. Patients with known central nervous system (CNS) involvement of ALL; 2. Diseases with abnormal heart, lung, liver, kidney, or other organ functions that may limit the patient's participation in this trial (including but not limited to severe infections, uncontrolled diabetes, severe heart failure or angina, active pulmonary tuberculosis, asthma, COPD, bronchiectasis, etc.); 3. Cardiac ultrasound LVEF < 45%; 4. History of other malignancies within the past 5 years, excluding localized thyroid cancer and in situ skin cancer; 5. Serum total bilirubin > 1.5 ULN (upper limit of normal); ALT or AST > 2.5 ULN; serum creatinine > 1.5 ULN; 6. Known HIV infection; 7. Conditions affecting the use of the study drug as assessed by the investigator; 8. Unable to understand or comply with the study protocol.

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 · 1 center

• The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang — Hangzhou

Publications

• Beldjord K, Chevret S, Asnafi V, Huguet F, Boulland ML, Leguay T, Thomas X, Cayuela JM, Grardel N, Chalandon Y, Boissel N, Schaefer B, Delabesse E, Cave H, Chevallier P, Buzyn A, Fest T, Reman O, Vernant JP, Lheritier V, Bene MC, Lafage M, Macintyre E, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Oncogenetics and minimal residual disease are independent ou PMID 24740809
• Lu J, Zhou H, Zhou X, Yang Y, Tong L, Miao M, Yang X, Chen S. Reduced-dose chemotherapy followed by blinatumomab in induction therapy for newly diagnosed B-cell acute lymphoblastic leukemia. Cancer Med. 2024 Mar;13(5):e7062. doi: 10.1002/cam4.7062. PMID 38491815
• 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 l PMID 37187201
• 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, PMID 39047240
• 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
• 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
• Kantarjian H, Thomas D, O'Brien S, Cortes J, Giles F, Jeha S, Bueso-Ramos CE, Pierce S, Shan J, Koller C, Beran M, Keating M, Freireich EJ. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004 Dec 15;101(12):2788-801. doi: 10.1002/cncr.20668. PMID 15481055
• Larson RA, Dodge RK, Burns CP, Lee EJ, Stone RM, Schulman P, Duggan D, Davey FR, Sobol RE, Frankel SR, et al. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood. 1995 Apr 15;85(8):2025-37. PMID 7718875

Identifiers

NCT: NCT06742515 · IIT20240126C

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗