Study of the BiTE® Blinatumomab (MT103) in Adult Patients With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL)

January 23, 2017 updated by: Amgen Research (Munich) GmbH

An Open Label, Multicenter, Exploratory Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of the BiTE® Antibody Blinatumomab in Adult Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)

The purpose of this study is to determine whether the bispecific T-cell engager blinatumomab is effective, safe and tolerable in the treatment of patients with relapsed/refractory B-precursor ALL.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Relapsed/refractory B-precursor ALL in adult patients is an aggressive malignant disease with dismal prognosis and unmet medical need. Additional therapeutic approaches are urgently needed. Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. The purpose of this study is to investigate the efficacy, safety and tolerability of different doses of the bispecific T-cell engager blinatumomab in adult patients with relapsed/refractory B-precursor ALL. Patrticipants will receive up to five 4-week cycles of intravenous blinatumomab treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Frankfurt, Germany
      • Freiburg, Germany
      • Hannover, Germany
      • Kiel, Germany
      • Münster, Germany
      • Regensburg, Germany
      • Tübingen, Germany
      • Ulm, Germany
      • Würzburg, Germany

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with B-precursor ALL relapsed after at least induction and consolidation or having refractory disease
  • More than 5% blasts in bone marrow
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Life expectancy of ≥ 12 weeks

Exclusion Criteria:

  • History or presence of clinically relevant central nervous system (CNS) pathology
  • Infiltration of cerebrospinal fluid (CSF) by ALL
  • Autologous/allogeneic hematopoietic stem cell transplantation (HSCT) within six weeks/three months prior to start of blinatumomab treatment
  • Active Graft-versus-Host Disease (GvHD)
  • Patients with Philadelphia chromosome (Ph)+ ALL eligible for treatment with dasatinib or imatinib
  • Cancer chemotherapy within two weeks prior to start of blinatumomab treatment
  • Immunotherapy (e.g. rituximab) within four weeks prior to start of blinatumomab treatment
  • Infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
  • Pregnant or nursing women
  • Previous treatment with blinatumomab

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Blinatumomab 15 μg
Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Biological: Blinatumomab
Continuous intravenous infusion over four weeks per treatment cycle
Other Names:
  • MT103
  • AMG103
  • BLINCYTO™
Experimental: Blinatumomab 5/15 μg
Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.
Biological: Blinatumomab
Continuous intravenous infusion over four weeks per treatment cycle
Other Names:
  • MT103
  • AMG103
  • BLINCYTO™
Experimental: Blinatumomab 5/15/30 μg
Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.
Biological: Blinatumomab
Continuous intravenous infusion over four weeks per treatment cycle
Other Names:
  • MT103
  • AMG103
  • BLINCYTO™

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment
Time Frame: Within the first 2 cycles of treatment, 12 weeks

At the end of each infusion period, a bone marrow aspiration/biopsy was performed to evaluate the efficacy of blinatumomab. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Hematological remissions were defined by the following criteria:

Complete Response/Remission (CR):

  • Less than or equal to 5% blasts in the bone marrow
  • No evidence of circulating blasts or extramedullar disease

  • Full recovery of peripheral blood counts:

    • Platelets > 100,000/μL
    • Hemoglobin ≥ 11 g/dL
    • Absolute neutrophil count (ANC) > 1,500/μL

Complete Remission with only Partial Hematological Recovery (CRh*):

  • Less than or equal to 5% blasts in the bone marrow
  • No evidence of circulating blasts or extramedullar disease

  • Partial recovery of peripheral blood counts:

    • Platelets > 50,000/μL
    • Hemoglobin ≥ 7 g/dL
    • ANC > 500/μL.
Within the first 2 cycles of treatment, 12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With a Best Response of Complete Remission Within 2 Cycles of Treatment
Time Frame: Within the first 2 cycles of treatment, 12 weeks

At the end of each infusion period, a bone marrow aspiration/biopsy was performed to evaluate the efficacy of blinatumomab. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Complete Response/Remission (CR) was defined by the following criteria:

  • Less than or equal to 5% blasts in the bone marrow
  • No evidence of circulating blasts or extramedullar disease

  • Full recovery of peripheral blood counts:

    • Platelets > 100,000/μL
    • Hemoglobin ≥ 11 g/dL
    • Absolute neutrophil count (ANC) > 1,500/μL
Within the first 2 cycles of treatment, 12 weeks
Percentage of Participants With a Best Response of Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment
Time Frame: Within the first 2 cycles of treatment, 12 weeks

At the end of each infusion period, a bone marrow aspiration/biopsy was performed to evaluate the efficacy of blinatumomab. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Complete remission with only partial hematological recovery (CRh*) was defined by the following criteria:

  • Less than or equal to 5% blasts in the bone marrow
  • No evidence of circulating blasts or extramedullar disease

  • Partial recovery of peripheral blood counts:

    • Platelets > 50,000/μL
    • Hemoglobin ≥ 7 g/dL
    • ANC > 500/μL.
Within the first 2 cycles of treatment, 12 weeks
Percentage of Participants With a Best Response of Partial Remission Within 2 Cycles of Treatment
Time Frame: Within the first 2 cycles of treatment, 12 weeks

At the end of each infusion period, a bone marrow aspiration/biopsy was performed to evaluate the efficacy of blinatumomab. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Partial remission was defined by the following criteria:

• Bone marrow blasts ≤ 25%
Within the first 2 cycles of treatment, 12 weeks
Percentage of Participants With a Minimal Residual Disease (MRD) Response During the Core Study
Time Frame: During the core study treatment period (up to 30 weeks).
A minimal residual disease (MRD) response is defined as MRD < 10^-4 blasts/nucleated cells based on polymerase chain reaction (PCR) evaluation of individual rearrangements of immunoglobulin or T cell receptor genes.
During the core study treatment period (up to 30 weeks).
Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) After Treatment With Blinatumomab
Time Frame: Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days
The percentage of participants who underwent immediate allogeneic HSCT (defined as those in remission who undergo HSCT without receiving any other treatments) after having discontinued or completed the core study.
Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days
Time to Hematological Relapse
Time Frame: Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days.

Time to hematological relapse was measured for participants who achieved a CR or CRh* during the core study and was measured from the time the participant first achieved remission until first documented relapse or death due to disease progression. Participants without a documented relapse (hematological or extramedullary) and who did not die were censored at the time of their last bone marrow assessment or their last survival follow-up visit confirming remission. Participants who died without having reported hematological relapse or without showing any clinical sign of disease progression were censored on their day of death.

Hematological Relapse was defined as:

  • Proportion of blasts in bone marrow > 5%
  • Extramedullary relapse.

Time to hematological relapse was analyzed by Kaplan-Meier methods.
Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days.
Relapse-free Survival
Time Frame: Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days.
Relapse-free survival was measured only for participants who achieved a CR or CRh* during the core study and was measured from the time the participant first achieved remission until first documented relapse or death due to any cause. Participants without a documented relapse (hematological or extramedullary) or who did not die were censored at the time of their last bone marrow assessment or their last survival follow-up visit confirming remission. Relapse-free survival was estimated using Kaplan-Meier methods.
Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days.
Overall Survival
Time Frame: Up to the data cut-off date of 15 October 2012; maximum follow up time was 667 days.
Overall survival was measured for all participants from the date of first infusion of blinatumomab until the date of death due to any cause. Participants who did not die were censored on the last documented visit date. Overall survival was estimated using Kaplan-Meier methods.
Up to the data cut-off date of 15 October 2012; maximum follow up time was 667 days.
Number of Participants With Treatment-emergent Adverse Events
Time Frame: From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle; median treatment duration was 55.7 days.

Adverse events were evaluated for severity according to the grading scale provided in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 and according to the following:

Grade I (mild); Grade 2 (moderate); Grade 3 (severe - significantly limits the patient's ability to perform routine activities despite symptomatic therapy; Grade 4 (life-threatening); Grade 5 (death).

The investigator used medical judgment to determine if there was a causal relationship (ie, certain, probable, possible, unlikely, not related) between an adverse event and blinatumomab.

A serious adverse event is any untoward medical occurrence or effect, that at any dose:

resulted in death, was life-threatening, required or prolonged hospitalization, resulted in persistent or significant disability or incapacity, is a congenital anomaly or birth defect or is a medically important condition.
From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle; median treatment duration was 55.7 days.
Steady State Blinatumomab Concentration
Time Frame: Samples were collected at predose and at 48 hours following start of infusion, when dose is escalated and on Days 8, 15, 22, and 29 of the first 2 cycles.

The steady state concentration of blinatumomab was summarized as the observed concentrations collected at least 10 hours after the intravenous infusion was started for cycle 1 and cycle 2, respectively. Actual doses administered were used in the analysis.

Concentrations below the limit of detection (3 pg/mL) were set to zero before data analysis and concentrations below the lower limit of quantitation (50 pg/mL) were excluded from analysis.
Samples were collected at predose and at 48 hours following start of infusion, when dose is escalated and on Days 8, 15, 22, and 29 of the first 2 cycles.
Clearance of Blinatumomab
Time Frame: Samples were collected at predose and at 48 hours following start of infusion, when dose is escalated and on Days 8, 15, 22, and 29 of the first 2 cycles.
Clearance was calculated as R0/Css; where R0 is the infusion rate (μg/m^2/hr) and Css is the steady state concentration.
Samples were collected at predose and at 48 hours following start of infusion, when dose is escalated and on Days 8, 15, 22, and 29 of the first 2 cycles.
Serum Cytokine Peak Levels
Time Frame: Samples were collected prior to treatment start (baseline), and at 2, 6, 24, and 48 hours after drug infusion start, and at these same time points when dose is escalated in each treatment cycle.
The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) is 125 pg/mL and the limit of detection (LOD) is 20 pg/mL.
Samples were collected prior to treatment start (baseline), and at 2, 6, 24, and 48 hours after drug infusion start, and at these same time points when dose is escalated in each treatment cycle.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amgen Research (Munich) GmbH

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Max Topp, MD, University of Wuerzburg

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 23, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 24, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 27, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 6, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MT103-206

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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