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

NCT03523429 | Terminated Phase 2

• 1 other identifier: PETHEMA-BLIN-01
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 12

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

Conditions

Philadelphia Chromosome-negative or BCR-ABL-negative, CD19-positive ALL

Outcome Measures

Primary Outcomes (1)

• To assess the reduction rate of the Minimal residual disease determined by Multiparametric flow cytometry

  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.

  1 year

Study Arms (1)

blinatumomab

EXPERIMENTAL

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

Interventions

blinatumomab DRUG

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

blinatumomab

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (12)

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital ICO Hospitalet

Barcelona, Spain

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

. Hospital Clínico Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital Central de Asturias

Oviedo, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, Spain

Location

C.H.U, de Santiago

Santiago de Compostela, Spain

Location

H. Virgen Del Rocio

Seville, Spain

Location

Hospital Universitario y Politécnico la Fe

Valencia, Spain

Location

MeSH Terms

Interventions

blinatumomab

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: May 1, 2018
• First Posted: May 14, 2018
• Study Start: June 30, 2018
• Primary Completion: December 24, 2019
• Study Completion: March 9, 2022
• Last Updated: July 27, 2022

Record last verified: 2022-07

Locations

ES (12)