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PETHEMA-BLIN-01/PET069014 (BLIN-01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03523429
Recruitment Status : Recruiting
First Posted : May 14, 2018
Last Update Posted : April 7, 2020
Sponsor:
Information provided by (Responsible Party):
PETHEMA Foundation

Brief Summary:

The PETHEMA Spanish group treats patients with high-risk Philadelphia chromosome-negative ALL, aged 18 to 55 years, based on the MRD clearance as assessed by flow cytometry at a centralised evaluation centre. Patients with MRD < 0.1% (< 1×10-3) after induction and < 0.01% (< 1×10-4) after early consolidation are assigned to receive chemotherapy (late consolidation and maintenance).

Early consolidation chemotherapy consists of three cycles including high doses of MTX, ARA-C and ASP, together with vincristine and dexamethasone. The same therapy is repeated in the late consolidation period if MRD after early consolidation is < 0.01% (< 1×10-4). Maintenance therapy is then administered for up to 2 years from the CR date. These patients do not receive allo-HSCT if they maintain adequate MRD clearance.

Despite having adequate MRD clearance, a proportion of patients (around 25%) experience relapse, which makes other approaches necessary to try to decrease the relapse rate. Intensifying currently existing chemotherapy regimens is not likely to increase the cure rate and would likely significantly increase toxicity. The use of targeted immunotherapeutic agents such as blinatumomab, which has demonstrated efficacy and safety in patients with R/R ALL and in patients with ALL and MRD+, seems to be a promising option [30-33].

Therefore, it would be interesting to assess the potential efficacy of using blinatumomab in CR patients to reduce the MRD more frequently and more intensely during the early and late consolidation period. Our hypothesis is that blinatumomab will further reduce the level of MRD and this could lead to a decrease in the relapse rate in these patients.

This trial will replace the third early consolidation cycle with a cycle of blinatumomab, and the same will be done in the late consolidation period. We hope that this strategy will increase the extent of the MRD response and prevent relapses.

Moreover, and as a secondary objective, we will investigate the safety of blinatumomab administration after the administration of high-dose chemotherapy including MTX, ARA-C and ASP


Condition or disease Intervention/treatment Phase
Philadelphia Chromosome-negative or BCR-ABL-negative, CD19-positive ALL Drug: blinatumomab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-label Study to Evaluate the Effect of Blinatumomab Administered During Consolidation to Reduce the Level of Minimal Residual Disease (MRD) Assessed Through Flow Cytometry in Adult Patients up to 55 Years of Age With High-risk Philadelphia Chromosome-negative (Ph-) Acute Lymphoblastic Leukaemia (ALL) With Good Response (MRD < 0.1%) After Induction Therapy
Actual Study Start Date : June 30, 2018
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024


Arm Intervention/treatment
Experimental: blinatumomab
blinatumomab administered during the early consolidation phase in patients ≤ 55 years with high-risk Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukaemia (ALL) with MRD < 0.1% (< 1×10-3) after induction therapy.
Drug: blinatumomab
Blinatumomab is a bispecific monoclonal antibody designed to bind specifically to CD19, expressed on the surface of B-cells, and to CD3, expressed on the surface of T-cells. It activates endogenous T-cells by connecting the CD3 on the T-cell receptor complex (TCR) with the CD19 on the B-cells. The anti-tumour activity of blinatumomab does not depend on whether the T-cells carry a specific TCR or peptide antigens present in cancer cells, but it is polyclonal and independent of HLA on the target cells




Primary Outcome Measures :
  1. To assess the reduction rate of the Minimal residual disease determined by Multiparametric flow cytometry [ Time Frame: 1 year ]
    To assess the reduction rate of the MRD determined by MFC, after early consolidation following the inclusion of blinatumomab administered during the early consolidation phase in patients ≤ 55 years of age with high-risk Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukaemia (ALL) with MRD < 0.1% (< 1×10-3) after induction therapy.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women between 18 to 55 years of age, both inclusive.
  • Patients with Philadelphia chromosome-negative or BCR-ABL-negative, CD19-positive ALL, with high-risk characteristics. The definition of high-risk ALL implies the presence of one or more of the following factors: Aged 30-55 years; Leukocytes > 30×109/l in B-precursor ALL; Any of the following cytogenetic or molecular abnormalities: 11q23 abnormalities, or proven MLL rearrangement; Complex karyotype (more than 5 chromosome abnormalities); Pro-B ALL, regardless of the number of leukocytes.
  • Previous treatment according to routine clinical practice in Spanish centres, in accordance with the PETHEMA protocol for patients with high-risk ALL (ALL-AR-11), in complete remission (MRD < 0.1%) (< 1×10-3) centralised assessment through flow cytometry) after induction therapy.
  • ECOG < 2.
  • Ability to understand the study and willingness to sign the written informed consent form

Exclusion Criteria:

  • Philadelphia chromosome-positive (Ph+) ALL.
  • Burkitt's leukaemia (mature B phenotype) according to the WHO classification.
  • T-cell ALL.
  • B-precursor ALL with high-risk characteristics and MRD ≥ 0.1% (≥ 1×10-3) after receiving induction chemotherapy.
  • Previous history or presence of a clinically significant disease of the central nervous system (CNS): epilepsy, seizures, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis.
  • Presence or history of an autoimmune disease potentially affecting the CNS.
  • Radiotherapy in the 2 weeks prior to starting treatment with blinatumomab.
  • Immunotherapy (e.g., rituximab) within 4 weeks prior to starting treatment with blinatumomab.
  • Any investigational product for leukaemia in the 4 weeks prior to starting treatment with blinatumomab.
  • Treatment with any investigational medicinal product after signing the informed consent form.
  • Candidate patient for allogeneic haematopoietic stem cell transplantation (HSCT) at the time of enrolment.
  • Known hypersensitivity to human immunoglobulins or to any component of the investigational product.
  • Abnormal laboratory values: AST (SGOT) and/or ALT (SGPT) and/or alkaline phosphatase ≥ 5 ULN;total bilirubin ≥ 1.5 ULN (unless related to Gilbert's syndrome or Meulengracht's disease); Creatinine ≥ 1.5 ULN; Estimated creatinine clearance < 50 ml/min; Haemoglobin ≥ 9 g/dl (transfusion permitted).
  • History of malignant disease other than ALL in the 5 years prior to starting treatment with blinatumomab, with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
  • Active uncontrolled infection, or any other concurrent disease or medical condition considered to interfere with the conduct of the study as per the investigator's discretion.
  • HIV infection or chronic hepatitis B virus (HBsAg positive) or hepatitis C virus infection (anti-HCV positive).
  • Pregnant or breast-feeding women.
  • Women of childbearing potential who are not willing use an effective method of contraception during their participation in the study and for at least 3 months thereafter. Men who are not willing to take measures to prevent their partner from becoming pregnant during their participation in the study and for at least 3 months thereafter.
  • Prior treatment with blinatumomab.
  • Patients who do not want or are unable to meet the protocol requirements

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03523429


Locations
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Spain
Hospital Germans Trias i Pujol and all Hospital Pethema Recruiting
Badalona, Barcelona, Spain
Contact: Jose Mª Ribera, Dr    93 465 12 00    jribera@iconcologia.net   
Hospital ICO Hospitalet Recruiting
Barcelona, Spain
Contact: Santiago Mercadal, Dr    932 607 733    smercadal@iconcologia.net   
Hospital Vall d'Hebron Recruiting
Barcelona, Spain
Contact: Barba Pere, Dr    + 34 934 89 30 00    pbarba@vhio.net   
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain
Contact: Pilar Martínez Sánchez, Dr    913908047    mariapilar.martinez.sanchez@salud.madrid.org   
. Hospital Clínico Universitario Virgen de la Victoria Recruiting
Málaga, Spain
Contact: Moreno Mª José, Dr    951 032 596    mjmorenorico@hotmail.com   
Hospital Central de Asturias Recruiting
Oviedo, Spain
Contact: Teresa Bernal del Castillo, Dr    + 34 985 108 000    teresa.bernal@sespa.es   
Hospital Clinico Universitario de Salamanca Recruiting
Salamanca, Spain
Contact: Jesús Maria Hernández Rivas, Dr    923 29 11 00    jmhr@usal.es   
H. Virgen Del Rocio Recruiting
Sevilla, Spain
Contact: José González Campos, Dr    955012218    jose.gonzalez.sspa@juntadeandalucia.es   
Hospital Universitario y Politécnico la Fe Recruiting
Valencia, Spain
Contact: Pau Montesinos, Dr    +34 963 86 27 00    montesinos_pau@gva.es   
Sponsors and Collaborators
PETHEMA Foundation
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Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT03523429    
Other Study ID Numbers: PETHEMA-BLIN-01
First Posted: May 14, 2018    Key Record Dates
Last Update Posted: April 7, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Philadelphia Chromosome
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Blinatumomab
Antineoplastic Agents