A study to about blinatumomab for patients with minimal residual disease (MRD) of acute lymphoblastic leukemia

Phase 1

Active, not recruiting

• Conditions: Patients with minimal residual disease (MRD) positive B-precursor ALL with and without prior SCT documented after an interval of at least 8 days from last systemic chemo-therapy• at a level of =10-4 - <10-3 (molecular failure or molecular relapse) in an assay with a minimum sensitivity of 10-4 OR• at levels below 10-4 :o Positive <10-4, non quantifiable (MolNE1) ORo Positive <10-4 (MolNE2) OR• Presence of minimal residual disease (MRD), non quantifiable (MolNE3).; MedDRA version: 21.1Level: LLTClassification code 10066104Term: Precursor B-lymphoblastic leukaemia acuteSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-000733-76-DE
• Lead Sponsor: Goethe-Universität Frankfurt, Universitätsklinikum, Med. Klinik II

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-03-02
• Last Update Posted: 26 September 2023

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Patients with CD19 positive B–precursor ALL in complete hematological remission defined as less than 5% blasts in bone marrow after at least three intense chemotherapy blocks (e.g., GMALL induction I-II/consolidation I).
2.Presence of minimal residual disease (MRD) after an interval of at least 8 days from last systemic chemo-therapy
•at a level of =10-4 - <10-3 (molecular failure or molecular relapse) in an assay with a minimum sensitivity of 10-4 OR
•at levels below 10-4 :
oPositive <10-4, non quantifiable (MolNE1) OR
oPositive <10-4 (MolNE2) OR
•Presence of minimal residual disease (MRD), non quantifiable (MolNE3).
3. For evaluation of MRD patients must have at least one molecular marker based on individual rearrange-ments of immunoglobulin, TCR-genes or other suitable genes evaluated by the reference laborabory of the trial
4. Bone marrow function as defined below:
- ANC (Neutrophils) >/= 1,000/µL
- Platelets >/= 50,000/µL (transfusion permitted)
- HB level >/= 9g/dl (transfusion permitted)
5. Renal and hepatic function as defined below:
- AST (GOT), ALT (GPT), and AP < 5 x upper limit of normal (ULN)
- Total bilirubin < 1.5 x ULN (unless related to Gilbert's Meulen-gracht disease)
- Creatinine < 1.5x ULN
- Creatinine clearance >/= 60 mL/min (e.g. calculated according Cockroft & Gault)
6. Negative HIV test, negative hepatitis B (HbsAg) and hepatitis C virus (anti-HCV) test
7. Negative pregnancy test in women of childbearing potential
8. ECOG Performance Status 0 or 1
9. Age min. 18 years
10. Ability to understand and willingness to sign a written informed consent
11. Signed and dated written informed consent is available
12. Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1. Ph/BCR-ABL positive ALL
2. Presence of circulating blasts or current extramedullary involvement by ALL
3. History or presence of clinically relevant CNS pathology (e.g. seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome or psychosis)
4. Current detection of ALL blast cells in cerebrospinal fluid
5. History of or active relevant autoimmune disease
6. Systemic cancer chemotherapy within 2 weeks prior to study treatment (except for intrathecal prophylaxis)
7. Radiotherapy within 4 weeks prior to study treatment
8. Live vaccination within 2 weeks before the start of study treatment
9. Autologous hematopoietic stem cell transplantation (SCT) within six weeks prior to study treatment
10. Allogeneic SCT within 12 weeks before the start of study treatment
11. Any active acute Graft-versus-Host Disease (GvHD), grade 2-4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment
12. Any systemic therapy against GvHD within 2 weeks before start of study treatment
13. Therapy with monoclonal antibodies (rituximab, alemtuzumab) within 4 weeks prior to study treatment
14. Treatment with any investigational product within four weeks prior to study treatment
15. Previous treatment with blinatumomab or other anti-CD19-therapy
16. Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation
17. History of malignancy other than ALL diagnosed within 5 years prior to start of protocol-specified therapy with the exception of:
- 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
18. Active infection, any other concurrent disease or medical condition that are deemed to interfere with the conduct of the study as judged by the investigator
19. Nursing women
20. Woman of childbearing potential and is not willing to use a highly effective method of contraception while receiving study treatment and for an additional 3 months after the last dose of study treatment.
21. Male who has a female partner of childbearing potential, and is not willing to use a highly effective form of contraception while receiving study treatment and for at least an additional 3 months after the last dose of study treatment

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified