Newly Diagnosed Clinical Trial
— Blina-CELLOfficial title:
Single Cycle of Blinatumomab Followed by High-dose Chemotherapy in the Induction Therapy for Ph-negative Acute Lymphoblastic Leukemia in Adults
Verified date | September 2023 |
Source | Institute of Hematology and Blood Transfusion, Czech Republic |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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
Status | Completed |
Enrollment | 27 |
Est. completion date | February 29, 2024 |
Est. primary completion date | February 29, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria: - 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. Exclusion Criteria: - 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; - Concurrent participation in another clinical study with an investigational medical product. |
Country | Name | City | State |
---|---|---|---|
Czechia | University Hospital Brno, Internal hematology and oncology clinic | Brno | |
Czechia | University Hospital Hradec Kralove,The 4th Department of Internal Medicine - Hematology | Hradec Králové | |
Czechia | University Hospital Olomouc, Hematooncology Clinic | Olomouc | |
Czechia | University Hospital Ostrava, Hematooncology Clinic | Ostrava | |
Czechia | Institute of Hematology and Blood Transfusion, Czech Republic | Prague |
Lead Sponsor | Collaborator |
---|---|
Institute of Hematology and Blood Transfusion, Czech Republic | CZECRIN - Czech Clinical Research Infrastructure Network |
Czechia,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. Erratum In: Lancet Oncol. 2015 Apr;16(4):e158. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Minimal Residual Disease (MRD) response | MRD response in bone marrow at the end of blinatumomab infusion (Induction cycle I) | End of blinatumomab infusion (End of the 1st Induction course which is 28 days); Day 40 of the study | |
Secondary | Progression Free Survival (PFS) | Progression-free survival (PFS) in patients treated with blinatumomab followed by chemotherapy in the induction therapy | 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 | |
Secondary | Overall Survival (OS) | Overall survival (OS) in patients treated with blinatumomab followed by chemotherapy in the induction therapy | Time between the start of leukemia-specific therapy (Day 1) until date of death of any cause, assessed up to 24 months | |
Secondary | AlloSCT | Percentage of patients undergoing allogeneic stem cell transplantation (alloSCT) due to the suboptimal molecular response after blinatumomab and chemotherapy | Week 18 ( after the completion of the 1st Consolidation cycle which is 21 days) | |
Secondary | Infectious complications during induction chemotherapy | Incidence of infectious complications during induction chemotherapy in patients treated with blinatumomab and chemotherapy | At week 11; after completion of two induction courses (1st Induction Course is 28 days) | |
Secondary | Incidence and severity of blinatumomab-related adverse events | incidence and severity of blinatumomab-related adverse events in the induction therapy | At week 11; after completion of two induction courses (1st Induction Course is 28 days) |
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