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

NCT ID: NCT03109093

Last Updated: 2023-03-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-15
• Study Completion Date: 2023-03-10

Brief 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. 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 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.

Conditions

ALL, Recurrent, Adult

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Blinatumomab

Intervention Type: DRUG

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.

Interventions

Blinatumomab

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.

Intervention Type: DRUG

Other Intervention Names

blincyto

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Goethe University

OTHER

Sponsor Role: lead

Responsible Party

Nicola Goekbuget

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nicola Goekbuget, MD

Role: PRINCIPAL_INVESTIGATOR

GMALL-Study-Group

Locations

University Hospital of Frankfurt (Main)

Frankfurt am Main, Hesse, Germany

Charité - Campus Benjamin Franklin

Berlin, , Germany

Uniklinik Dresden

Dresden, , Germany

Uniklinik Düsseldorf

Düsseldorf, , Germany

Univeristätsklinikum Essen

Essen, , Germany

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitätsmedizin Göttingen

Göttingen, , Germany

Uniklinik Hamburg Eppendorf

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Uniklinik Heidelberg

Heidelberg, , Germany

UKSH-Kiel

Kiel, , Germany

Universitätsklinik Leipzig

Leipzig, , Germany

Klinikum Mannheim

Mannheim, , Germany

Universitätsklinkum Gießen und Marburg

Marburg, , Germany

Klinikum Großhadern

München, , Germany

Uniklinik Münster

Münster, , Germany

Klinikum Nürnberg Nord

Nuremberg, , Germany

Uniklinik Regensburg

Regensburg, , Germany

Robert - Bosch - Krankenhaus

Stuttgart, , Germany

Universitätsklinik Tübingen

Tübingen, , Germany

Universitätsklinkum Ulm

Ulm, , Germany

Uniklinik Würzburg

Würzburg, , Germany

Countries

Germany

References

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.

Reference Type: RESULT

Other Identifiers

2015-000733-76

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GMALL-MOLACT1-BLINA

Identifier Type: -

Identifier Source: org_study_id