Blinatumomab Followed by High-dose Chemotherapy for Ph-negative Acute Lymphoblastic Leukemia (ALL)

NCT04554485 | Completed Phase 2

• 1 other identifier: Blina-CELL
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 5

Brief Summary

This is a phase II interventional trial to evaluate the efficacy of blinatumomab followed by high-dose chemotherapy in the first-line treatment for Ph-negative acute lymphoblastic leukemia (ALL) in adults. The aim is to increase the number of complete molecular responses after first two cycles of therapy. Early molecular response is considered to be the most powerful prognostic factor in ALL. Thus, a higher proportion of early molecular responses should translate into improved survival and fewer indications for allogeneic stem cell transplants

Conditions

Lymphoblastic Leukemia, Acute, Adult; Ph Negative ALL; Newly Diagnosed

Outcome Measures

Primary Outcomes (1)

• Complete Molecular Response

  Percentage of complete molecular responses after two cycles of induction therapy composed of a single cycle of blinatumomab followed by chemotherapy

  At week 11 (acceptable window +2wks); after completion of two induction courses (1st Induction Course is 28 days) and before starting of the 1st Consolidation cycle at week 13

Secondary Outcomes (6)

• Minimal Residual Disease (MRD) response

  End of blinatumomab infusion (End of the 1st Induction course which is 28 days); Day 40 of the study

• Progression Free Survival (PFS)

  Time from the day of CR/CRi documentation until the date of relapse, or death from any cause whichever came first, assessed up to 24 months

• Overall Survival (OS)

  Time between the start of leukemia-specific therapy (Day 1) until date of death of any cause, assessed up to 24 months

• AlloSCT

  Week 18 ( after the completion of the 1st Consolidation cycle which is 21 days)

• Infectious complications during induction chemotherapy

  At week 11; after completion of two induction courses (1st Induction Course is 28 days)

Study Arms (1)

Blinatumomab followed by high-dose chemotherapy

EXPERIMENTAL

Single cycle of blinatumomab followed by high-dose chemotherapy in the induction therapy for Ph-negative acute lymphoblastic leukemia in adults

Drug: Blinatumomab

Interventions

Blinatumomab DRUG

Single cycle of blinatumomab followed by high-dose chemotherapy in the induction therapy for Ph-negative acute lymphoblastic leukemia in adults

Also known as: BLINCYTO; AMG103; L01XC19

Blinatumomab followed by high-dose chemotherapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years;
• Lymphoblasts positive for CD19;
• Eligible to intensive chemotherapy, due to general health status;
• With newly diagnosed B-precursor-ALL;
• Without BCR-ABL fusion by FISH analysis and/or RT-PCR;
• Blasts expressing the CD19 antigen by flow cytometry;
• Previously untreated;
• ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2;
• Diagnostic sample of bone marrow (or peripheral blood with \>50% of blasts) available for central MRD assessment
• Written informed consent obtained prior to any screening procedures.

You may not qualify if:

• History of malignancy other than ALL within 5 years prior to start of protocol-required therapy, except for:
• Malignancy treated with curative intent and with no known active disease present for 5 years before enrollment and felt to be at low risk for recurrence by the treating physician;
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
• Adequately treated cervical carcinoma in situ without evidence of disease;
• Adequately treated breast ductal carcinoma in situ without evidence of disease;
• Prostatic intraepithelial neoplasia without evidence of prostate cancer.
• History or presence of central nervous system (CNS) pathology as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis;
• Persisting ALL in the CNS at the end of run-in period; patients with initial cerebrospinal fluid (CSF) infiltration arriving into CSF negativity after up to 4 intrathecal applications of chemotherapy within the first 10 days of therapy are allowed for the study;
• Current autoimmune disease or history of autoimmune disease with potential CNS involvement;
• Active known hepatitis B virus (HBV) or hepatitis C virus (HCV) or positive HIV serology;
• Hypersensitivity to any active substance contained in blinatumomab, including polysorbate 80;
• Vaccination with a live virus vaccine within 4 weeks prior to the study enrolment;
• Female patients who are pregnant or breast feeding or patients of childbearing potential not willing to use a double barrier method of contraception during the study and for 3 months following the last dose of study drug;
• Male patients whose sexual partner(s) are women of childbearing potential who are not willing to use a double barrier method of contraception, one of which includes a condom, during the study;
• Any of concurrent severe and/or uncontrolled medical condition, which could, in the opinion of the investigator, compromise participation in the study;

Sponsors & Collaborators

• Institute of Hematology and Blood Transfusion, Czech Republic: lead
• CZECRIN - Czech Clinical Research Infrastructure Network: collaborator

Study Sites (5)

University Hospital Brno, Internal hematology and oncology clinic

Brno, 60200, Czechia

Location

University Hospital Hradec Kralove,The 4th Department of Internal Medicine - Hematology

Hradec Králové, 50005, Czechia

Location

University Hospital Olomouc, Hematooncology Clinic

Olomouc, 77900, Czechia

Location

University Hospital Ostrava, Hematooncology Clinic

Ostrava, 70852, Czechia

Location

Institute of Hematology and Blood Transfusion, Czech Republic

Prague, 12800, Czechia

Location

Related Publications (8)

• Bruggemann M, Schrauder A, Raff T, Pfeifer H, Dworzak M, Ottmann OG, Asnafi V, Baruchel A, Bassan R, Benoit Y, Biondi A, Cave H, Dombret H, Fielding AK, Foa R, Gokbuget N, Goldstone AH, Goulden N, Henze G, Hoelzer D, Janka-Schaub GE, Macintyre EA, Pieters R, Rambaldi A, Ribera JM, Schmiegelow K, Spinelli O, Stary J, von Stackelberg A, Kneba M, Schrappe M, van Dongen JJ; European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL); International Berlin-Frankfurt-Munster Study Group (I-BFM-SG). Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. Leukemia. 2010 Mar;24(3):521-35. doi: 10.1038/leu.2009.268. Epub 2009 Dec 24.

  PMID: 20033054 BACKGROUND

• 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.

  PMID: 28249141 BACKGROUND

• Mastrangelo R, Poplack D, Bleyer A, Riccardi R, Sather H, D'Angio G. Report and recommendations of the Rome workshop concerning poor-prognosis acute lymphoblastic leukemia in children: biologic bases for staging, stratification, and treatment. Med Pediatr Oncol. 1986;14(3):191-4. doi: 10.1002/mpo.2950140317. No abstract available.

  PMID: 3528788 BACKGROUND

• Salek C, Folber F, Fronkova E, Prochazka B, Marinov I, Cetkovsky P, Mayer J, Doubek M; Czech Leukemia Study Group - for Life. Early MRD response as a prognostic factor in adult patients with acute lymphoblastic leukemia. Eur J Haematol. 2016 Mar;96(3):276-84. doi: 10.1111/ejh.12587. Epub 2015 Jun 22.

  PMID: 25997106 BACKGROUND

• Topp MS, Gokbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, Dombret H, Fielding AK, Heffner L, Larson RA, Neumann S, Foa R, Litzow M, Ribera JM, Rambaldi A, Schiller G, Bruggemann M, Horst HA, Holland C, Jia C, Maniar T, Huber B, Nagorsen D, Forman SJ, Kantarjian HM. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015 Jan;16(1):57-66. doi: 10.1016/S1470-2045(14)71170-2. Epub 2014 Dec 16.

  PMID: 25524800 BACKGROUND

• Topp MS, Gokbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S, Viardot A, Marks R, Diedrich H, Faul C, Reichle A, Horst HA, Bruggemann M, Wessiepe D, Holland C, Alekar S, Mergen N, Einsele H, Hoelzer D, Bargou RC. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014 Dec 20;32(36):4134-40. doi: 10.1200/JCO.2014.56.3247. Epub 2014 Nov 10.

  PMID: 25385737 BACKGROUND

• Topp MS, Kufer P, Gokbuget N, Goebeler M, Klinger M, Neumann S, Horst HA, Raff T, Viardot A, Schmid M, Stelljes M, Schaich M, Degenhard E, Kohne-Volland R, Bruggemann M, Ottmann O, Pfeifer H, Burmeister T, Nagorsen D, Schmidt M, Lutterbuese R, Reinhardt C, Baeuerle PA, Kneba M, Einsele H, Riethmuller G, Hoelzer D, Zugmaier G, Bargou RC. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol. 2011 Jun 20;29(18):2493-8. doi: 10.1200/JCO.2010.32.7270. Epub 2011 May 16.

  PMID: 21576633 BACKGROUND

• van der Velden VH, Cazzaniga G, Schrauder A, Hancock J, Bader P, Panzer-Grumayer ER, Flohr T, Sutton R, Cave H, Madsen HO, Cayuela JM, Trka J, Eckert C, Foroni L, Zur Stadt U, Beldjord K, Raff T, van der Schoot CE, van Dongen JJ; European Study Group on MRD detection in ALL (ESG-MRD-ALL). Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia. 2007 Apr;21(4):604-11. doi: 10.1038/sj.leu.2404586. Epub 2007 Feb 8.

  PMID: 17287850 BACKGROUND

Related Links

• Acute Lymphocytic Leukemia
• Blinatumomab

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Cyril Salek, MD

  Institute of Hematology and Blood Transfusion, Czech Republic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2020
• First Posted: September 18, 2020
• Study Start: May 9, 2019
• Primary Completion: February 29, 2024
• Study Completion: February 29, 2024
• Last Updated: April 4, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (5)