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

NCT03109093 | Completed Phase 2

• 2 other identifiers: GMALL-MOLACT1-BLINA2015-000733-76
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 22

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.

Conditions

ALL, Recurrent, Adult

Keywords

ALL; acute lymphoblastic leukemia; MRD positive; minimal residual disease; blinatumomab

Outcome Measures

Primary Outcomes (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

  after one cycle of treatment (up to 43 days)

Secondary Outcomes (14)

• Continuous complete remission

  18 months following initiation of blinatumomab

• Hematological relapse-free survival

  18 months following initiation of blinatumomab

• Overall survival

  18 months following initiation of blinatumomab

• Relapse localisations

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

• Biological evaluation of hematological and extramedullary relapse

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

Other Outcomes (8)

• Treatment deviation1

  until end of treatment (up to 22 weeks)

• Treatment deviation2

  until end of treatment (up to 22 weeks)

• Treatment deviation3

  until end of treatment (up to 22 weeks)

Study Arms (1)

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.

Drug: Blinatumomab

Interventions

Blinatumomab 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.

Also known as: blincyto

Blinatumomab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Goethe University: lead

Study Sites (22)

University Hospital of Frankfurt (Main)

Frankfurt am Main, Hesse, 60590, Germany

Location

Charité - Campus Benjamin Franklin

Berlin, Germany

Location

Uniklinik Dresden

Dresden, Germany

Location

Uniklinik Düsseldorf

Düsseldorf, Germany

Location

Univeristätsklinikum Essen

Essen, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Universitätsmedizin Göttingen

Göttingen, Germany

Location

Uniklinik Hamburg Eppendorf

Hamburg, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Uniklinik Heidelberg

Heidelberg, Germany

Location

UKSH-Kiel

Kiel, Germany

Location

Universitätsklinik Leipzig

Leipzig, Germany

Location

Klinikum Mannheim

Mannheim, Germany

Location

Universitätsklinkum Gießen und Marburg

Marburg, Germany

Location

Klinikum Großhadern

München, Germany

Location

Uniklinik Münster

Münster, Germany

Location

Klinikum Nürnberg Nord

Nuremberg, Germany

Location

Uniklinik Regensburg

Regensburg, Germany

Location

Robert - Bosch - Krankenhaus

Stuttgart, Germany

Location

Universitätsklinik Tübingen

Tübingen, Germany

Location

Universitätsklinkum Ulm

Ulm, Germany

Location

Uniklinik Würzburg

Würzburg, Germany

Location

Related Publications (1)

• 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.

  RESULT

MeSH Terms

Conditions

Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasm, Residual

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes

Study Officials

• Nicola Goekbuget, MD

  GMALL-Study-Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 13, 2017
• First Posted: April 12, 2017
• Study Start: March 15, 2017
• Primary Completion: August 15, 2021
• Study Completion: March 10, 2023
• Last Updated: March 21, 2023

Record last verified: 2023-03

Locations

DE (22)