Non-Hodgkin's Lymphoma, Relapsed
Conditions
Keywords
Non-Hodgkin's Lymphoma, Cancer immunotherapy, Monoclonal antibody, anti-CD19, anti-CD3, BiTE, Blinatumomab
Brief summary
The purpose of this study is to determine whether a continuous infusion of Blinatumomab (MT103) is safe in the treatment of relapsed Non-Hodgkin's Lymphoma. Furthermore, the study is intended to provide pharmacokinetic and pharmacodynamic data of Blinatumomab as well as to get first indication of tumour activity.
Detailed description
Non-Hodgkin's Lymphoma (NHL) represents the 6th most common cancer. Globally, around 165,000 new cases are diagnosed each year, with approximately 90,000 deaths per year. The vast majority of NHLs are B-cell derived (90%) and express common B-cell antigens such as CD19, CD20 and CD22. NHL can be divided into indolent (low-grade) and aggressive (high-grade) lymphomas. Still almost all patients with advanced stage indolent disease will die from their disease. Therefore, a high medical need exists to develop novel agents that further improve the survival of NHL patients. Blinatumomab (MT103) is a bispecific antibody derivative, anti-CD19 x anti-CD3, designed to link B-cells and T-cells resulting in T-cell activation and a cytotoxic T-cell response against CD19+ cells. Data of prior phase I studies show evidence of biological activity in humans. In vitro and ex-vivo data suggest that a longterm presence of the drug in target tissues may provide antitumour activity. The study investigates the safety and tolerability of different doses of Blinatumomab administration in a continuous infusion regimen. Maximum tolerated dose (MTD) will be defined in a classical 3+3 dose escalation regimen.
Interventions
BIOLOGICALBlinatumomab (MT103)
Doses from 0.5 to 120 µg/m\^2/24hours by continuous intravenous infusion
Sponsors
Amgen Research (Munich) GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with first or later relapse of histologically (World Health Organisation classification) confirmed: * follicular lymphoma (grade I/II) * marginal zone lymphoma * lymphoplasmocytic lymphoma * mantle cell lymphoma * diffuse large B-cell lymphoma * small lymphocytic lymphoma requiring therapy and not eligible for curative treatment 2. Measurable disease (at least one lesion \>= 1.5 cm) documented by computed tomography (CT) scan 3. Age \>= 18 years 4. Eastern Cooperative Oncology Group (ECOG) performance status \<=2 5. Life expectancy of at least 6 months 6. Ability to understand the patient information and informed consent form 7. Signed and dated written informed consent is available 8. B:T cell ratio (Fluorescence-Activated Cell Sorter \[FACS\] analysis results by central lab) available before study entry.
Exclusion criteria
1. Any other NHL not listed in inclusion criterion 1 2. Abnormal laboratory values as defined below: * Peripheral lymphocyte count \> 20 x 10\^9/L * Platelet counts ≤ 75,000/µL * Hemoglobin level ≤ 9 g/dL * Venous pH value out of normal range or oxygen saturation ≤ 90% 3. Known or suspected central nervous system (CNS) involvement by NHL 4. a)History of or current relevant CNS pathology as epilepsy, seizure, paresis,aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis b)Evidence for presence of inflammatory lesions and/or vasculitis on cerebral MRI 5. Autologous stem cell transplantation within 12 weeks prior to study entry 6. Allogeneic stem cell transplantation 7. Cancer chemotherapy within 4 weeks prior to study entry 8. Radiotherapy within 4 weeks prior to study entry 9. Treatment with rituximab within 4 weeks prior to study entry 10. Prior treatment with alemtuzumab 12 weeks prior to study entry 11. Treatment with any investigational agent within 12 weeks prior to study entry 12. Contraindication for any of the concomitant medications 13. Abnormal renal or hepatic function as defined below: * Aspartate aminotransferase (AST; SGOT) and/or alanine aminotransferase (ALT; SGPT) \>= 2 x upper limit of normal (ULN) * total bilirubin \>= 1.5 x ULN * serum creatinine \>= 2 x ULN * creatinine clearance \< 50mL/min 14. Indication of hypercoagulative state as defined below: -antithrombin activity \<LLN 15. Presence of human anti-murine antibodies (HAMA) or known hypersensitivity to immunoglobulins 16. History of malignancy other than B-cell lymphoma within 5 years prior to study entry, with the exception of basal cell carcinoma of the skin or carcinoma in situ of the cervix 17. Active infection / not yet recovered from recent infection; known bacteriemia 18. Any concurrent disease or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator 19. Regular dose of corticosteroids during the four weeks prior to D1 of this study or anticipated need of corticosteroids exceeding prednisone 20 mg/day or equivalent, or any other immunosuppressive therapy within 4 weeks prior to study entry 20. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B or hepatitis C virus 21. Pregnant or nursing women, or women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. Male patients not willing to ensure that during the study and at least three months thereafter no fathering takes place.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From the first infusion of blinatumomab until the safety follow-up visit 2 weeks after end of the treatment period, including the consolidation and relapse periods. The median treatment duration was 33.24 days. | Participants reporting at least one occurence of any adverse event including clinical symptoms, laboratory abnormalities, serious adverse events, and treatment-limiting adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentration of Blinatumomab | Up to 24 hours after the end of infusion. | The steady state serum concentration (Css), summarized as the observed concentrations collected at least 10 hours after the start of continuous intravenous infusion or within the sampling window at the end of infusion. Concentrations below the lower limit of quantitation (100 pg/mL) were excluded from analysis. |
| Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Assessed after 4 and 8 weeks of treatment | Tumor response was defined according to the Cheson criteria and assessed after 4 and 8 weeks of study treatment using computed tomography (CT) scan (neck, thorax and abdomen/pelvic to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Best clinical response is defined as the best response achieved during the course of the study, with response defined as: Complete Response, Complete Response Unconfirmed, Partial Response, Stable Disease, and Progressive Disease. In this analysis minimal response is set to stable disease as intended in the response categories according to the Cheson criteria. An independent external review by a radiologist (computed tomography scans) and a pathologist (biopsies) was performed to confirm response status. If no post-baseline tumor assessment was available, the overall clinical response was set to not available. |
| Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Assessed after 4 and 8 weeks of treatment | Tumor response was defined according to the Cheson criteria and assessed after 4 and 8 weeks of study treatment using computed tomography (CT) scan (neck, thorax and abdomen/pelvic to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Minimal response was treated as a separate response category in this analysis. Best clinical response was defined as the best response achieved during the course of the study, whereby the following order was applied: Complete Response, Complete Response Unconfirmed, Partial Response, Minimal Response, Stable Disease, and Progressive Disease. If no post-baseline tumor assessment was available, the overall clinical response was set to not available. |
Countries
Germany
Participant flow
Recruitment details
Participants were enrolled from 22 June 2004 through 18 July 2011
Pre-assignment details
Participants were enrolled into 20 different cohorts representing different dose levels, modes of administration (ramp, single-step, double-step, flat), or populations. To facilitate the analysis of the study, the different cohorts were grouped into six dose groups based on the dose that was intended to be given to a participant.
Participants by arm
| Arm | Count |
|---|---|
| Blinatumomab ≤ 5 µg/m²/d Participants received blinatumomab ≤ 5 µg/m²/day as continuous intravenous infusion over 4-8 weeks in the first treatment cycle. | 12 |
| Blinatumomab 15 µg/m²/d Participants received blinatumomab 15 µg/m²/day as continuous intravenous infusion over 4-8 weeks in the first treatment cycle. | 13 |
| Blinatumomab 30 µg/m²/d Participants received blinatumomab 30 µg/m²/day as continuous intravenous infusion over 4-8 weeks in the first treatment cycle. | 6 |
| Blinatumomab 60 µg/m²/d Flat Participants received blinatumomab 60 µg/m²/day without a lower dose as continuous intravenous infusion over 4-8 weeks in the first treatment cycle. | 9 |
| Blinatumomab 60 µg/m²/d Step Participants received blinatumomab 60 μg/m²/day as continuous intravenous infusion after initial lower doses of 5 and/or 15 μg/m²/day for a total treatment duration of 4-8 weeks in the first treatment cycle. | 32 |
| Blinatumomab 90 µg/m²/d Participants received blinatumomab 90 µg/m²/day as continuous intravenous infusion over 4-8 weeks in the first treatment cycle. | 4 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 | 1 | 4 | 12 | 3 |
| Overall Study | Disease Progression | 0 | 1 | 1 | 0 | 1 | 0 |
| Overall Study | End of Study | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 0 | 3 | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Blinatumomab ≤ 5 µg/m²/d | Total | Blinatumomab 90 µg/m²/d | Blinatumomab 60 µg/m²/d Step | Blinatumomab 60 µg/m²/d Flat | Blinatumomab 30 µg/m²/d | Blinatumomab 15 µg/m²/d |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.8 years STANDARD_DEVIATION 7.5 | 60.3 years STANDARD_DEVIATION 12.4 | 64.8 years STANDARD_DEVIATION 5.6 | 57.1 years STANDARD_DEVIATION 14.9 | 59.7 years STANDARD_DEVIATION 11.9 | 53.3 years STANDARD_DEVIATION 9.4 | 64.8 years STANDARD_DEVIATION 8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 76 Participants | 4 Participants | 32 Participants | 9 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Female | 2 Participants | 19 Participants | 1 Participants | 11 Participants | 0 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 57 Participants | 3 Participants | 21 Participants | 9 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 12 | 13 / 13 | 6 / 6 | 9 / 9 | 32 / 32 | 4 / 4 | 76 / 76 |
| serious Total, serious adverse events | 8 / 12 | 10 / 13 | 6 / 6 | 9 / 9 | 22 / 32 | 4 / 4 | 59 / 76 |
Outcome results
Primary
Number of Participants With Adverse Events
Participants reporting at least one occurence of any adverse event including clinical symptoms, laboratory abnormalities, serious adverse events, and treatment-limiting adverse events
Time frame: From the first infusion of blinatumomab until the safety follow-up visit 2 weeks after end of the treatment period, including the consolidation and relapse periods. The median treatment duration was 33.24 days.
Population: All participants who received at least one infusion of blinatumomab
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Blinatumomab ≤ 5 µg/m²/d | Number of Participants With Adverse Events | 12 participants |
| Blinatumomab 15 µg/m²/d | Number of Participants With Adverse Events | 13 participants |
| Blinatumomab 30 µg/m²/d | Number of Participants With Adverse Events | 6 participants |
| Blinatumomab 60 µg/m²/d Flat | Number of Participants With Adverse Events | 9 participants |
| Blinatumomab 60 µg/m²/d Step | Number of Participants With Adverse Events | 32 participants |
| Blinatumomab 90 µg/m²/d | Number of Participants With Adverse Events | 4 participants |
Secondary
Objective Tumor Response According to the Cheson Criteria (With Minimal Response)
Tumor response was defined according to the Cheson criteria and assessed after 4 and 8 weeks of study treatment using computed tomography (CT) scan (neck, thorax and abdomen/pelvic to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Minimal response was treated as a separate response category in this analysis. Best clinical response was defined as the best response achieved during the course of the study, whereby the following order was applied: Complete Response, Complete Response Unconfirmed, Partial Response, Minimal Response, Stable Disease, and Progressive Disease. If no post-baseline tumor assessment was available, the overall clinical response was set to not available.
Time frame: Assessed after 4 and 8 weeks of treatment
Population: All participants who received at least one infusion of blinatumomab
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Complete response | 0 participants |
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Stable disease | 5 participants |
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Complete response unconfirmed | 0 participants |
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Not available | 0 participants |
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Partial response | 0 participants |
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Progressive disease | 6 participants |
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Minimal response | 1 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Complete response unconfirmed | 0 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Minimal response | 1 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Partial response | 2 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Stable disease | 6 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Complete response | 1 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Not available | 0 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Progressive disease | 3 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Partial response | 0 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Complete response unconfirmed | 0 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Complete response | 1 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Stable disease | 1 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Progressive disease | 2 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Minimal response | 1 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Not available | 1 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Minimal response | 0 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Complete response | 3 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Complete response unconfirmed | 0 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Partial response | 5 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Stable disease | 0 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Progressive disease | 0 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Not available | 1 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Partial response | 6 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Complete response unconfirmed | 5 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Not available | 2 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Complete response | 5 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Progressive disease | 7 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Minimal response | 2 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Stable disease | 5 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Not available | 1 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Stable disease | 0 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Partial response | 1 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Complete response unconfirmed | 0 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Progressive disease | 0 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Complete response | 1 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (With Minimal Response) | Minimal response | 1 participants |
Secondary
Objective Tumor Response According to the Cheson Criteria (Without Minimal Response)
Tumor response was defined according to the Cheson criteria and assessed after 4 and 8 weeks of study treatment using computed tomography (CT) scan (neck, thorax and abdomen/pelvic to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Best clinical response is defined as the best response achieved during the course of the study, with response defined as: Complete Response, Complete Response Unconfirmed, Partial Response, Stable Disease, and Progressive Disease. In this analysis minimal response is set to stable disease as intended in the response categories according to the Cheson criteria. An independent external review by a radiologist (computed tomography scans) and a pathologist (biopsies) was performed to confirm response status. If no post-baseline tumor assessment was available, the overall clinical response was set to not available.
Time frame: Assessed after 4 and 8 weeks of treatment
Population: All participants who received at least one infusion of blinatumomab
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Complete response unconfirmed | 0 participants |
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Progressive disease | 6 participants |
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Complete response | 0 participants |
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Partial response | 0 participants |
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Not available | 0 participants |
| Blinatumomab ≤ 5 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Stable disease | 6 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Complete response | 1 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Partial response | 2 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Progressive disease | 3 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Not available | 0 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Complete response unconfirmed | 0 participants |
| Blinatumomab 15 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Stable disease | 7 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Complete response unconfirmed | 0 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Not available | 1 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Stable disease | 2 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Partial response | 0 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Progressive disease | 2 participants |
| Blinatumomab 30 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Complete response | 1 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Stable disease | 0 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Complete response unconfirmed | 0 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Partial response | 5 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Complete response | 3 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Progressive disease | 0 participants |
| Blinatumomab 60 µg/m²/d Flat | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Not available | 1 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Stable disease | 7 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Progressive disease | 7 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Partial response | 6 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Complete response | 5 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Not available | 2 participants |
| Blinatumomab 60 µg/m²/d Step | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Complete response unconfirmed | 5 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Complete response | 1 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Stable disease | 1 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Progressive disease | 0 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Partial response | 1 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Not available | 1 participants |
| Blinatumomab 90 µg/m²/d | Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) | Complete response unconfirmed | 0 participants |
Secondary
Serum Concentration of Blinatumomab
The steady state serum concentration (Css), summarized as the observed concentrations collected at least 10 hours after the start of continuous intravenous infusion or within the sampling window at the end of infusion. Concentrations below the lower limit of quantitation (100 pg/mL) were excluded from analysis.
Time frame: Up to 24 hours after the end of infusion.
Population: Participants who received blinatumomab and had available pharmacokinetic data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinatumomab ≤ 5 µg/m²/d | Serum Concentration of Blinatumomab | 210 pg/mL | Standard Deviation 84.9 |
| Blinatumomab 15 µg/m²/d | Serum Concentration of Blinatumomab | 651 pg/mL | Standard Deviation 307 |
| Blinatumomab 30 µg/m²/d | Serum Concentration of Blinatumomab | 1210 pg/mL | Standard Deviation 476 |
| Blinatumomab 60 µg/m²/d Flat | Serum Concentration of Blinatumomab | 2730 pg/mL | Standard Deviation 985 |
| Blinatumomab 60 µg/m²/d Step | Serum Concentration of Blinatumomab | 3490 pg/mL | Standard Deviation 904 |