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ALL, Recurrent, AdultPhase 2NCT03109093

Blinatumomab in Adult Patients With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia

A Phase 2 study testing Blinatumomab in people with ALL, Recurrent, Adult, run by Goethe University at 22 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
ALL, Recurrent, Adult
What is being tested?
Blinatumomab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
22 sitesGermany
Study dates
15 Mar 2017to 10 Mar 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

Germany22 sites

  • Charité - Campus Benjamin Franklin

    Berlin

  • Uniklinik Dresden

    Dresden

  • Uniklinik Düsseldorf

    Düsseldorf

  • Univeristätsklinikum Essen

    Essen

  • University Hospital of Frankfurt (Main)

    Frankfurt am Main, Hesse, 60590

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau

  • Universitätsmedizin Göttingen

    Göttingen

  • Uniklinik Hamburg Eppendorf

    Hamburg

  • Medizinische Hochschule Hannover

    Hanover

  • Uniklinik Heidelberg

    Heidelberg

  • UKSH-Kiel

    Kiel

  • Universitätsklinik Leipzig

    Leipzig

  • Klinikum Mannheim

    Mannheim

  • Universitätsklinkum Gießen und Marburg

    Marburg

  • Klinikum Großhadern

    München

  • Uniklinik Münster

    Münster

  • Klinikum Nürnberg Nord

    Nuremberg

  • Uniklinik Regensburg

    Regensburg

  • Robert - Bosch - Krankenhaus

    Stuttgart

  • Universitätsklinik Tübingen

    Tübingen

  • Universitätsklinkum Ulm

    Ulm

  • Uniklinik Würzburg

    Würzburg

Other trials in Germany

About this study

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)

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.

Read the detailed description

Transfer of patients to alloHSCT after one cycle or after a subsequent cycle 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.

Being tested
Blinatumomab
Keywords
ALL, acute lymphoblastic leukemia, MRD positive, minimal residual disease, blinatumomab
Medical subject headings
Recurrence, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasm, Residual

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BlinatumomabDrug

    Also called blincyto

    Patients will receive blinatumomab at a dose of 28 µg/day as continuous intravenous infusion at constant flow rate for four weeks, followed by a two-week infusion free interval, defined as one treatment cycle. Up to of four cycles will be performed.

    In case of defined toxicities, the dose of blinatumomab may be reduced to 9µg/day.

    Patients with an MRD relapse may qualify to receive additional treatment with blinatumomab.

Study groups in NCT03109093
Study groupRoleWhat they receive
BlinatumomabExperimentalPatients 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.
Receives: Drug: Blinatumomab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MRD response after one cycle

    Proportion of patients who achieve complete MRD response after one cycle of treatment with blinatumomab in patients with and without prior SCT

    Measured: after one cycle of treatment (up to 43 days)

Secondary outcomes (14)

  1. Continuous complete remission

    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)

    Measured: 18 months following initiation of blinatumomab

  2. Hematological relapse-free survival

    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)

    Measured: 18 months following initiation of blinatumomab

  3. Overall survival

    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)

    Measured: 18 months following initiation of blinatumomab

  4. Relapse localisations

    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)

    Measured: In Case of Relapse, continuously until End of Follow-Up (up to 18 Months)

  5. Biological evaluation of hematological and extramedullary relapse

    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)

    Measured: In Case of Relapse, continuously until End of Follow-Up (up to 18 Months)

  6. Serious Adverse Event (SAE) incidence

    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)

    Measured: continuously until End of Safety-Follow-Up (up to 26 weeks)

  7. MRD response after two cycles

    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)

    Measured: after two cycles of treatment (up to 85 days)

  8. complete MRD response after two cycles

    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)

    Measured: after two cycles of treatment (up to 85 days)

  9. duration of MRD response

    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)

    Measured: 18 months following initiation of blinatumomab

  10. Time to MRD response

    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)

    Measured: MRD determination after each cycle of treatment (up to 24 weeks)

  11. GvHD

    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)

    Measured: until End of Safety-Follow-Up (up to 26 weeks)

  12. treatment related mortality after subsequent SCT

    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)

    Measured: after subsequent SCT (at day 100 and later)

  13. treatment related mortality

    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)

    Measured: continuously until End of Follow-Up (up to 18 Months)

  14. Quality of Life

    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)

    Measured: until End of Follow-Up (up to 18 Months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Apr 2017
  2. Study start15 Mar 2017
  3. Primary completion15 Aug 2021
  4. Study completion10 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03109093
Sponsor's protocol ID
GMALL-MOLACT1-BLINA
Other IDs
2015-000733-76, 2015
Status last verified
Mar 2023
First submitted
13 Mar 2017
Last updated
21 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Gökbuget N, et al . Interim Results of a Multicenter, Single-Arm Study to Assess Blinatumomab in Adult Patients (pts) with Minimal Residual Disease (MRD) of B-Precursor (BCP) Acute Lymphoblastic Leukemia (GMALL-MOLACT1-BLINA). Blood (2020) 136 (Supplement 1): 39-40.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Blinatumomab in people with ALL, Recurrent, Adult, run by Goethe University at 22 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MRD response after one cycle (time frame: after one cycle of treatment (up to 43 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03109093, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2023.

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