Blinatumomab in Adult Patients With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia
ALL, Recurrent, Adult
About this trial
This is an interventional treatment trial for ALL, Recurrent, Adult focused on measuring ALL, acute lymphoblastic leukemia, MRD positive, minimal residual disease, blinatumomab
Eligibility Criteria
Inclusion Criteria:
- 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).
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 documented after an interval of at least 2 weeks from last systemic chemotherapy OR
at levels below 10-4 documented after an interval of at least 2 weeks from last systemic chemotherapy:
- Positive <10-4, non quantifiable (MolNE1) OR
- Positive <10-4 (MolNE2) OR
- Presence of minimal residual disease (MRD), non quantifiable (MolNE3).
- For evaluation of MRD patients must have at least one molecular marker based on individual rearrangements of immunoglobulin, TCR-genes or other suitable genes evaluated by the reference laboratory of the trial
Bone marrow function as defined below:
- ANC (Neutrophils) >= 1,000/µL
- Platelets >= 50,000/µL (transfusion permitted)
- HB level >= 9g/dl (transfusion permitted)
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 Meulengracht disease)
- Creatinine < 1.5x ULN
- Creatinine clearance >= 60 mL/min (e.g. calculated according Cockroft&Gault)
- Negative HIV test, negative hepatitis B (HbsAg) and hepatitis C virus (anti-HCV) test
- Negative pregnancy test in women of childbearing potential
- ECOG Performance Status 0 or 1
- Age >=18 years
- Ability to understand and willingness to sign a written informed consent
- Signed and dated written informed consent is available
- Participation in the registry of the German Multicenter Study Group for Adult ALL (GMALL)
Exclusion Criteria:
- Ph/BCR-ABL positive ALL
- Presence of circulating blasts or current extramedullary involvement by ALL
- 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)
- Current detection of ALL blast cells in cerebro-spinal fluid
- History of or active relevant autoimmune disease
- Systemic cancer chemotherapy within 2 weeks prior to study treatment (except for intrathecal prophylaxis)
- Radiotherapy within 4 weeks prior to study treatment
- Live vaccination within 2 weeks before the start of study treatment
- Autologous hematopoietic stem cell transplantation (SCT) within six weeks prior to study treatment
- Allogeneic SCT within 12 weeks before the start of study treatment
- Any active acute Graft-versus-Host Disease (GvHD), grade 2-4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment
- Any systemic therapy against GvHD within 2 weeks before start of study treatment
- Therapy with monoclonal antibodies (rituximab, alemtuzumab) within 4 weeks prior to study treatment
- Treatment with any investigational product within four weeks prior to study treatment
- Previous treatment with blinatumomab or other anti-CD19-therapy
- Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation
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
- 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
- Nursing women
- Woman of childbearing potential and is not willing to use 2 highly effective methods of contraception while receiving study treatment and for an additional 3 months after the last dose of study treatment.
- Male who has a female partner of childbearing potential, and is not willing to use 2 highly effective forms of contraception while receiving study treatment and for at least an additional 3 months after the last dose of study treatment
Sites / Locations
- University Hospital of Frankfurt (Main)
- Charité - Campus Benjamin Franklin
- Uniklinik Dresden
- Uniklinik Düsseldorf
- Univeristätsklinikum Essen
- Universitätsklinikum Freiburg
- Universitätsmedizin Göttingen
- Uniklinik Hamburg Eppendorf
- Medizinische Hochschule Hannover
- Uniklinik Heidelberg
- UKSH-Kiel
- Universitätsklinik Leipzig
- Klinikum Mannheim
- Universitätsklinkum Gießen und Marburg
- Klinikum Großhadern
- Uniklinik Münster
- Klinikum Nürnberg Nord
- Uniklinik Regensburg
- Robert - Bosch - Krankenhaus
- Universitätsklinik Tübingen
- Universitätsklinkum Ulm
- Uniklinik Würzburg
Arms of the Study
Arm 1
Experimental
Blinatumomab
Patients will receive four cycles of treatment, unless criteria for treatment discontinuation apply. The duration of one cycle is 6 weeks, including a four week continuous intravenous infusion and a two week infusion free interval, which may be extended by a maximum of 7 days. Patients entered with MRD level <10-4 (non quantifiable/MolNE1, quantifiable/MolNE2) or positive MRD, non quantifiable (MolNE3) will receive up to two cycles of Blinatumomab. Transfer of patients to alloHSCT after one cycle or after subsequent cycles is considered as per protocol discontinuation and as premature treatment discontinuation In case of hematological or extramedullary relapse, the study treatment will be permanently discontinued.