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Lymphoblastic Leukemia, Acute, AdultPhase 2Blina-CELLNCT04554485

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

A Phase 2 study testing Blinatumomab in people with Lymphoblastic Leukemia, Acute, Adult and Ph Negative ALL, run by Institute of Hematology and Blood Transfusion, Czech Republic at 5 sites in Czechia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Blinatumomab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
5 sitesCzechia
Study dates
9 May 2019to 29 Feb 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
Show all 10Show fewer
  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Czechia5 sites

  • University Hospital Brno, Internal hematology and oncology clinic

    Brno, 60200

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

    Hradec Králové, 50005

  • University Hospital Olomouc, Hematooncology Clinic

    Olomouc, 77900

  • University Hospital Ostrava, Hematooncology Clinic

    Ostrava, 70852

  • Institute of Hematology and Blood Transfusion, Czech Republic

    Prague, 12800

Other trials in Czechia

About this study

Official title: Single Cycle of Blinatumomab Followed by High-dose Chemotherapy in the Induction Therapy for Ph-negative Acute Lymphoblastic Leukemia in Adults

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

Read the detailed description

Primary Objective:

To evaluate the percentage of complete molecular responses after two cycles of induction therapy composed of a single cycle of blinatumomab followed by chemotherapy. Molecular response id monitored by a patient-specific Ig/TCR rearrangements in an assay with the sensitivity of at least 10e-04.

Outline:

Run-in phase: dexamethasone 10 mg/m2 PO (day 1-7), cyclophosphamide IV 200 mg/m2 (day 3-5), vincristine 2 mg IV (day 6), daunorubicin 45 mg/m2 IV (day 6-7), G-CSF until recovery, methotrexate 15 mg IT.

Day 11: Screening to the study. Induction I: blinatumomab 9 µg/day IV continuously (day 12-19), dose step to 28 µg/day (day 19-40). Induction II: dexamethasone 10 mg/m2 PO (day 50-54), vindesine 3 mg/m2 IV (day 50), methotrexate 1.5 g/m2 IV (day 50), etoposide 250 mg/m2 IV (day 53-54), cytarabine 2x 2 g/m2 IV (day 54), G-CSF until recovery, methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 60).

Week 11: Primary endpoint assessment.

  • Complete Remission (CR) and Complete Remission with incomplete blood count recovery(CRi) continue with Consolidation I;
  • no CR/CRi: end of study, salvage regimen upon the investigator´s decision.

Consolidation I (week 13): rituximab 375 mg/ m2 IV (day 0, if CD20+ at diagnosis), methotrexate 1.5 g/m2 IV (day 1, 15), PEG-asparaginase 2000 U/m2 IV (day 2, 16), 6-MP 60 mg/m2 PO (day 1-7, 15-21), methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 1).

Week 18 assessment:

  • CR/CRi and MRD <10-4: continue the protocol;
  • CR/CRi and MRD ≥10-4;
  • and CR/CRi on day 40 or ≥50% reduction of bone marrow blasts on day 40: 1-2 cycles of blinatumomab followed by alloSCT;
  • and no CR/CRi on day 40 and <50% reduction of bone marrow blasts on day 40: 1 cycle of high dose chemotherapy followed by alloSCT;
  • relapse: end of study.

Consolidation II (week 19): rituximab 375 mg/ m2 IV (day 0, if CD20+ at diagnosis), prednisone 60 mg/m2 PO (day 1-14), vindesine 3 mg/m2 IV (day 1, 7), adriamycine 50 mg/m2 IV (day 1, 7), cyclophosphamide 1000 mg/m2 IV (day 15), cytarabine 75 mg/m2 IV (day 17-20, 24-27), thioguanine 60 mg/m2 PO (day 15-28), methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 1), methotrexate 15 mg IT (day 17, 24). Consolidation III+VI (week 27 and 43): rituximab 375 mg/ m2 IV (day 0, if CD20+ at diagnosis), methotrexate 1.5 g/m2 IV (day 1, 15), PEG-asparaginase 2000 U/m2 IV (day 2, 16), 6-MP 60 mg/m2 PO (day 1-7, 15-21). Consolidation IV (week 33): rituximab 375 mg/ m2 IV (day 0, if CD20+ at diagnosis), cytarabine 1000 mg/m2 IV (day 1, 3, 5), methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 8). Consolidation V (week 38): rituximab 375 mg/ m2 IV (day 0, if CD20+ at diagnosis), cyclophosphamide 1000 mg/m2 IV (day 1), cytarabine 500 mg/m2 IV (day 1), methotrexate 15 mg + cytarabine 40 mg + dexamethasone 4 mg IT (day 1).

Maintenance (start at week 49, duration 12 months): 6-MP 60 mg/m2 PO daily, methotrexate 20 mg/m2 weekly.

(Doses of daunorubicin, methotrexate, cytarabine and PEG-asparaginase are reduced in patients >55 years.)

Being tested
Blinatumomab
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BlinatumomabDrug

    Also called BLINCYTO; AMG103; L01XC19

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

Study groups in NCT04554485
Study groupRoleWhat they receive
Blinatumomab followed by high-dose chemotherapyExperimentalSingle cycle of blinatumomab followed by high-dose chemotherapy in the induction therapy for Ph-negative acute lymphoblastic leukemia in adults
Receives: Drug: Blinatumomab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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)

  1. Minimal Residual Disease (MRD) response

    MRD response in bone marrow at the end of blinatumomab infusion (Induction cycle I)

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

  2. Progression Free Survival (PFS)

    Progression-free survival (PFS) in patients treated with blinatumomab followed by chemotherapy in the induction therapy

    Measured: 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

  3. Overall Survival (OS)

    Overall survival (OS) in patients treated with blinatumomab followed by chemotherapy in the induction therapy

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

  4. AlloSCT

    Percentage of patients undergoing allogeneic stem cell transplantation (alloSCT) due to the suboptimal molecular response after blinatumomab and chemotherapy

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

  5. Infectious complications during induction chemotherapy

    Incidence of infectious complications during induction chemotherapy in patients treated with blinatumomab and chemotherapy

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

  6. Incidence and severity of blinatumomab-related adverse events

    incidence and severity of blinatumomab-related adverse events in the induction therapy

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2020
  2. Study start9 May 2019
  3. Primary completion29 Feb 2024
  4. Study completion29 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04554485
Sponsor's protocol ID
Blina-CELL
Acronym
Blina-CELL
Status last verified
Sep 2023
First submitted
7 Sep 2020
Last updated
4 Apr 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 20033054

  • 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.

    PubMed 28249141

  • 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.

    PubMed 3528788

  • 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.

    PubMed 25997106

  • 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.

    PubMed 25524800

  • 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.

    PubMed 25385737

  • 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.

    PubMed 21576633

  • 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.

    PubMed 17287850

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Blinatumomab in people with Lymphoblastic Leukemia, Acute, Adult and Ph Negative ALL, run by Institute of Hematology and Blood Transfusion, Czech Republic at 5 sites in Czechia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Molecular Response (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04554485, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2024.

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