Description:
This study is designed to confirm the efficacy, safety, and tolerability of blinatumomab in
patients with MRD of B- precursor ALL in complete hematological remission including patients
with relapse after SCT. The study aims to expand experience generated in previous trials in
patients with MRD positive ALL with a focus on additional specific questions.
Title
- Brief Title: Blinatumomab in Adult Patients With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia
- Official Title: A Multicenter, Single-arm Study to Assess the Efficacy, Safety, and Tolerability of the BiTE® Antibody Blinatumomab in Adult Patients With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia (Blast Successor Trial)
Clinical Trial IDs
- ORG STUDY ID:
GMALL-MOLACT1-BLINA
- SECONDARY ID:
2015-000733-76
- NCT ID:
NCT03109093
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Blinatumomab | blincyto | Blinatumomab |
Purpose
This study is designed to confirm the efficacy, safety, and tolerability of blinatumomab in
patients with MRD of B- precursor ALL in complete hematological remission including patients
with relapse after SCT. The study aims to expand experience generated in previous trials in
patients with MRD positive ALL with a focus on additional specific questions.
Detailed Description
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.
There will be a safety follow-up visit at 30 days after end of the last infusion. There will
be efficacy follow-up until 18 months after treatment start. In patients scheduled for SCT
the 30-day safety-visit may be performed at the latest time point possible before initiation
of subsequent treatment.
Trial Arms
Name | Type | Description | Interventions |
---|
Blinatumomab | Experimental | 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. | |
Eligibility Criteria
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 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).
3. 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
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 Meulengracht 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 >=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)
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 cerebro-spinal 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 2 highly effective methods
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 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | MRD response after one cycle |
Time Frame: | after one cycle of treatment (up to 43 days) |
Safety Issue: | |
Description: | Proportion of patients who achieve complete MRD response after one cycle of treatment with blinatumomab in patients with and without prior SCT |
Secondary Outcome Measures
Measure: | Continuous complete remission |
Time Frame: | 18 months following initiation of blinatumomab |
Safety Issue: | |
Description: | Probability of continuous complete remission (remission duration) at 18 months following initiation of blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | Hematological relapse-free survival |
Time Frame: | 18 months following initiation of blinatumomab |
Safety Issue: | |
Description: | Probability of hematological relapse-free survival rate at 18 months following initiation of blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | Overall survival |
Time Frame: | 18 months following initiation of blinatumomab |
Safety Issue: | |
Description: | Probability of overall survival at 18 months following initiation of blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | Relapse localisations |
Time Frame: | In Case of Relapse, continuously until End of Follow-Up (up to 18 Months) |
Safety Issue: | |
Description: | Frequency of different relapse localisations in proportion to total hematological relapses (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | Biological evaluation of hematological and extramedullary relapse |
Time Frame: | In Case of Relapse, continuously until End of Follow-Up (up to 18 Months) |
Safety Issue: | |
Description: | Biological evaluation of hematological and extramedullary relapses including CD19 expression (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | Serious Adverse Event (SAE) incidence |
Time Frame: | continuously until End of Safety-Follow-Up (up to 26 weeks) |
Safety Issue: | |
Description: | Overall incidence and severity of adverse events in patients with and without prior SCT (CTCAE 4.0) (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | MRD response after two cycles |
Time Frame: | after two cycles of treatment (up to 85 days) |
Safety Issue: | |
Description: | Proportion of patients who achieve MRD response after one or two cycles of treatment with Blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | complete MRD response after two cycles |
Time Frame: | after two cycles of treatment (up to 85 days) |
Safety Issue: | |
Description: | Proportion of patients who achieve complete MRD response after two cycles of treatment with blinatumomab in patients with and without prior SCT (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | duration of MRD response |
Time Frame: | 18 months following initiation of blinatumomab |
Safety Issue: | |
Description: | Probability of continuous MRD response and complete MRD response and duration of MRD response at 18 months following initiation of blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | Time to MRD response |
Time Frame: | MRD determination after each cycle of treatment (up to 24 weeks) |
Safety Issue: | |
Description: | Time to MRD response measured by time-point of first achievement (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | GvHD |
Time Frame: | until End of Safety-Follow-Up (up to 26 weeks) |
Safety Issue: | |
Description: | Evaluation of GvHD as part of AE documentation and according to Glucksberg Criteria, grade and localisation. (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | treatment related mortality after subsequent SCT |
Time Frame: | after subsequent SCT (at day 100 and later) |
Safety Issue: | |
Description: | Evaluation of overall survival, remission duration, relapse-free survival and treatment related mortality (at day 100 and later) in patients with SCT in complete remission after blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | treatment related mortality |
Time Frame: | continuously until End of Follow-Up (up to 18 Months) |
Safety Issue: | |
Description: | Evaluation of overall survival, remission duration, relapse-free survival and treatment related mortality in patients without SCT in complete remission after blinatumomab (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Measure: | Quality of Life |
Time Frame: | until End of Follow-Up (up to 18 Months) |
Safety Issue: | |
Description: | Measurement of Quality of Life with EORTC instruments (EORTC QLQ C30 and EQ-5D) at different time-points during treatment (Separate analysis of all outcome parameters in patients with MRD above 10-4, 10-4-10-3 and patients with MRD below 10-4 or non-quantifiable MRD) |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Goethe University |
Trial Keywords
- ALL
- acute lymphoblastic leukemia
- MRD positive
- minimal residual disease
- blinatumomab
Last Updated
July 26, 2021