Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoproliferative Disorders

Lymphoma, B-Cell

Immunoproliferative Disorders

Lymphatic Diseases

Neoplasms by Histologic Type

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Bispecific

Immunoglobulins

Blinatumomab

By study design, two dose regimens were assessed in this study. In Stage 1, Cohort 1, participants received blinatumomab in a dose-escalating manner: 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during cycle 1. In Cohort 2, the next participants enrolled and received a constant dose of 112 µg/day blinatumomab. The dosing regimen with the more favorable benefit-risk profile was then selected for Stage 2, Cohort 3.

Administered by continuous intravenous infusion over 8 weeks in the first cycle and 4 weeks in the second cycle.

- MD

The purpose of this study is to confirm whether the bispecific T-cell engager blinatumomab is effective and safe in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

DLBCL is an aggressive malignant disease which evolves from B-cells and affects mainly the lymphatic tissue. Due to its aggressive nature the disease is characterized by a fast course which is lethal without therapy. Potentially curative therapy options are available even at advanced stages. Standard-first line leads to a high initial response rate (85-90%) and an approximate cure rate of 50% of patients. Patients refractory to or with early relapse after this treatment (10-15%) have a very poor prognosis.

Blinatumomab is a bispecific single-chain antibody derivative against CD19 and CD3, designed to link B-cells and T-cells resulting in T-cell activation and a cytotoxic T-cell response against CD19 expressing cells.

This study consisted of a screening period, treatment period, and a follow-up efficacy and survival period. The core study comprises the treatment period to the 30 days after the last infusion. The first cycle consisted of a continuous intravenous (CIV) infusion over 8 weeks. Participants who achieved a Complete Response (CR) or Partial Response (PR) or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval. After the last treatment cycle, efficacy and survival follow-up visits occurred for up to 24 months from treatment start. Participants who relapsed during the follow-up period may have received an additional 8 weeks of treatment.

Two dose regimens were assessed in this study. Stage 1 comprised 2 dose cohorts. In Cohort 1, the first 6 participants were to receive blinatumomab in a dose-escalating manner: 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. In Cohort 2, the next 6 participants enrolled were to receive a constant dose of 112 µg/day blinatumomab. Before the initiation of stage 2, a pre-planned data monitoring committee (DMC) meeting was held to assess the safety profile of Cohort 1 and Cohort 2. The dosing regimen with the more favorable benefit-risk profile was to be selected for Cohort 3.

Clinical Study With Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

An Open Label, Multicenter, Exploratory Phase 2 Study to Evaluate the Efficacy and Safety of the Bispecific T-Cell Engager (BiTE®) Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Overall response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Overall objective response rate (ORR) is the percentage of participants with a best overall response of complete response (CR) or partial response (PR).

Complete response is defined as the disappearance of all evidence of disease and partial response is defined as regression of measureable disease and no new sites.

Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Complete response is defined as the disappearance of all evidence of disease.

Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Partial response is defined as regression (\<50% decrease in size of masses) of measureable disease and no new sites.

The time from documentation of the first assessment of either partial or complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.

The time from documentation of the first assessment of complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.

The time from documentation of the first assessment of partial response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.

The time from the date of first blinatumomab infusion until the date of diagnosis of progression of lymphoma, the start date of new anti-tumor treatment (excluding any stem cell transplantation) or date of death, whichever is the earliest. Patients alive who did not have progression or new anti-tumor treatment (excluding any stem cell transplantation) were censored at last date of tumor assessment.

The time from the date of first blinatumomab infusion until death as a result of any cause. Patients still alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive. For patients who withdrew their informed consent, only information until the date of withdrawal was analyzed.

Adverse events were evaluated for severity according to the grading scale provided in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

An adverse event or suspected adverse drug reaction was considered "serious" if it resulted in one of the following outcomes:

* Resulted in death;
* Was life-threatening;
* Required inpatient hospitalization or prolongation of existing hospitalization;
* Resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions;
* Was a congenital anomaly or birth defect;
* Was a medically important condition.

The Investigator used medical judgment to determine whether there was a causal relationship (ie, related \[reasonably possible\] or unrelated \[not reasonably possible\]) between an adverse event and blinatumomab.

Blinatumomab serum levels were analyzed using a validated cluster of differentiation (CD)69 activation bioassay with a lower limit of quantification (LLOQ) of 50 pg/mL. Steady-state concentration (Css) was based on actual dose received, rather than based on cohort or time or day.

Leukocyte (white blood cells) counts were analyzed by differential blood count analysis.

Lymphocyte counts were analyzed by differential blood count analysis.

CD19+ B-cell counts were analyzed by flow cytometry.

CD3+ T-cell counts were analyzed by flow cytometry.

CD4+ T-cell counts were analyzed by flow cytometry.

CD8+ T-cell counts were analyzed by flow cytometry.

CD19+ B-cells and CD3+ T-cell counts were analyzed by flow cytometry.

CD4+ T-cells and CD8+ T-cell counts were analyzed by flow cytometry.

CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.

Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.

Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.

CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.

Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry.

Amgen Research (Munich) GmbH

Adverse Events were not pre-specified to be monitored/assessed after 10 July 2014.

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Participants received blinatumomab administered CIV 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. Participants who achieved a CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

Cohort 1: Blinatumomab 9/28/112 µg/d

Participants received blinatumomab administered CIV at a constant dose of 112 µg/day for 8 weeks of treatment during Cycle 1. Participants who achieved CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

Cohort 2: Blinatumomab 112 µg/d

Participants received blinatumomab administered CIV 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. Participants who achieved CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

Cohort 3: Blinatumomab 9/28/112 µg/d

Cohort 1+3: Blinatumomab 9/28/112µg/d

All participants who received blinatumomab by continuous intravenous infusion during the core study.

Blinatumomab Overall

Participants received blinatumomab administered via a continuous intravenous infusion (CIV) 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. Participants who achieved a complete response (CR) or partial response (PR), or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

Participants received blinatumomab administered CIV at a constant dose of 112 µg/day for 8 weeks of treatment during Cycle 1. Participants who achieved a CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

Total

Age, Continuous

Gender

White

Race/Ethnicity, Customized

Relapsed

Refractory

Relapsed/refractory Status to Last Prior Treatment

None

≥ 1

Number of Previous Autologous Hematopoietic Stem Cell Transplants (HSCT)

Study Director

Cohort 1: Blinatumomab 9/28/112 μg/d

Participants received blinatumomab CIV at a constant dose of 112 µg/day for 8 weeks of treatment during Cycle 1. Participants who achieved a CR or PR, or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval.

Cohort 2: Blinatumomab 112 μg/d

Cohort 3: Blinatumomab 9/28/112 μg/d

Efficacy Set includes all participants who completed at least 7 days of infusion on the highest intended dose level.

Overall Objective Response Rate During Treatment Cycle 1

Percentage of Participants With a Best Overall Response of Complete Response

Percentage of Participants With a Best Overall Response of Partial Response

Efficacy set with an overall objective response of CR or PR during the first treatment cycle

Duration of Objective Response

Efficacy set with a best overall response of CR during the first treatment cycle

Duration of Complete Response

Efficacy set with a best overall response of PR during the first treatment cycle

Duration of Partial Response

Progression-free Survival (PFS)

Overall Survival (OS)

Any adverse event (AE)

AE of Grade ≥ 3

AE of Grade ≥ 4

Serious adverse event (SAE)

Fatal adverse events

Led to discontinuation of study drug

Led to interruption of study drug

Related adverse events

Related AE Grade ≥ 3

Related AE Grade ≥ 4

Serious related adverse events

Related AE led to discontinuation of study drug

Related AE led to interruption of study drug

Number of Participants With Adverse Events

Participants received blinatumomab administered via a continuous intravenous infusion (CIV) 9 µg/day.

Blinatumomab 9 μg/d

Participants received blinatumomab CIV 28 µg/day.

Blinatumomab 28 μg/d

Participants received blinatumomab administered CIV 112 µg/day.

Blinatumomab 112 μg/d

Pharmacokinetic (PK) data set (all participants who received any infusion of blinatumomab and had at least one PK sample collected).

Blinatumomab Steady State Serum Concentration

Screening (N = 25)

Day 1 Prior (N = 24)

Day 8 (N = 21)

Day 15 (N = 16)

Day 29 (N = 11)

Day 43 (N = 8)

End of Infusion (N = 9)

End of Core Study (N = 6)

3-Month Follow-up (N = 5)

6-Month Follow-up (N = 6)

9-Month Follow-up (N = 4)

12-Month Follow-up (N = 4)

15-Month Follow-up (N = 3)

18-Month Follow-up (N = 3)

21-Month Follow-up (N = 21)

24-Month Follow-up (N = 3)

Enrolled participants with available data at each time point. All participants are included in pre-infusion and follow-up data points, only those participants in Cohorts 1 and 3 who had the same treatment schedule of 9/28/112 µg/day step dosing are included in the infusion time points (day 8 through end of infusion).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Clinical Study With Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)	NCT01741792	Diffuse Large B...	Blinatumomab	18 Years -	Amgen Research (Munich) GmbH
Clinical Study With Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)	NCT01741792	Diffuse Large B...	Blinatumomab	18 Years -	Amgen Research (Munich) GmbH

Spots Global Cancer Trial Database for adult dlbcl

Every month we try and update this database with for adult dlbcl cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for adult dlbcl

Every month we try and update this database with for adult dlbcl cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for adult dlbcl cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.