A Study Of Blinatumomab For The Treatment Of Relapsed Or... | NCT02811679

NCT02811679

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Amgen	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Blinatumomab	Experimental	Blinatumomab will be administered as a continuous IV infusion through a central venous catheter for a 42 day cycle. Blinatumomab will start with a 7 day infusion at 9mcg/d. If no dose limiting toxicity (table 6.1) after 7 days, the dose will be escalated to 28 mcg/d for 7 additional days. If no dose limiting toxicity (table 6.1) after 14 days, blinatumomab will be infused at a target dose of at 112mcg/d for 28 days. Subjects will be restaged after a 6 week treatment free period by PET CT. All subjects without disease progression will receive an additional 4 week cycle starting at the target dose of 112 mcg/d.	Drug: Blinatumomab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Blinatumomab	Drug	Blinatumomab is a bispecific t cell engaging antibody targeting CD19 and CD3 approved for B cell acute lymphoblastic leukemia	Blinatumomab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Response Rate (ORR)	Count of participants achieving a complete or partial response according to the revised response criteria for malignant lymphoma (2014). A complete response is defined as regression of involved nodes to normal size (1.5 cm or less in their greatest transverse diameter for nodes 1.5 cm or greater before therapy). Involved nodes 1.1 - 1.5 cm in their greatest transverse diameter before treatment must have decreased to less than 1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). For a complete response, the spleen, if enlarged before therapy on a CT scan, must also have regressed in size and must not be palpable. A partial response is defined as 50% or greater decrease in SPD of up to 6 largest dominant masses. There must also be no new sites of disease or increases in the size of the other nodes, liver, or spleen. Splenic/hepatic nodules must regress by at least 50% in SPD.	at completion of treatment (6 months)

Secondary Outcomes

Measure	Description	Time Frame
Progression Free Survival	Progression free survival is defined as the duration of time from start of treatment to time of documentation of disease progression according to the revised response criteria for malignant lymphoma (2014), death, or loss to follow-up. Progressive disease is defined as appearance of a new PET positive lesion greater than 1.5 cm in any axis, 50% or greater increase in the sum of the products of the greatest diameters (SPD) of more than one node, 50% or greater increase in longest diameter of a previously identified node less than 1 cm in short axis. There must also be a 50% increase from nadir in the SPD of any previous lesions.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects must have histologically determined B cell NHL that is relapsed or primary refractory after initial therapy.
- Follicular Lymphoma of any grade
- Marginal zone lymphoma (extranodal, nodal, or splenic). Patients with gastric MALT must have progressed after H. Pylori therapy and radiation. Patients with splenic MZL must have prior splenectomy.
At least 1 prior line of chemoimmunotherapy if primary refractory or relapsed with in one year. Subjects who respond to initial therapy for greater than one year must have had at least 2 prior lines of therapy including one line with chemoimmunotherapy including an anti-CD20 monoclonal antibody
Measurable disease that has not been previously irradiated on PET-CT of at least 1.5cm,
Age ≥18 years.
ECOG performance status ≤2 ( see Appendix A)
Participants must have adequate organ and marrow function as defined below:
- absolute neutrophil count ≥750/mcL
- platelets ≥75,000/mcL
- total bilirubin < 2.0 x upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal or 5 X ULN
- if due to lymphoma infiltration
- creatinine 2.0 X ULN OR
- creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels above 2.0 X ULN .
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Participants who have had chemotherapy within 3 weeks, rituximab or obinutuzumab within 4 weeks, or radioimmunotherapy within 6 weeks prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. Subjects actively progressing within that window who have recovered from toxicities of prior therapy are also eligible.
Autologous stem cell transplantation within 12 weeks prior to study entry
Prior allogeneic transplant
Therapeutic doses of corticosteroids within 14 days prior to study entry, defined as >20mg/day pf prednisone, or equivalent. Topical and/or inhaled steroids are permitted.
Participants who are receiving any other investigational agents.
Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to blinatumomab
Subjects with known HIV infection
Pregnant or lactating subjects.
Chronic infection with hepatitis B or hepatitis C virus
History of or current relevant CNS pathology such as epilepsy, seizure, paresis,aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis
Prior history of another malignancy (except for non-melanoma skin cancer, in situ cervical or breast cancer, or localized prostate cancer) unless disease free for at least one year and felt at low risk of relapse by treating physician.
Uncontrolled intercurrent illness including, but not limited to, ongoing or uncontrolled systemic fungal, bacterial, viral, or other infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Name	Affiliation	Role
Jeffrey Barnes, MD, PhD	Massachusetts General Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Massachusetts general Hospital		Boston	Massachusetts	02114	United States

Arm/Group Information

ID	Title	Description
FG000	Blinatumomab	Blinatumomab will be administered as a continuous IV infusion through a central venous catheter for a 42 day cycle. Blinatumomab will start with a 7 day infusion at 9mcg/d. If no dose limiting toxicity (table 6.1) after 7 days, the dose will be escalated to 28 mcg/d for 7 additional days. If no dose limiting toxicity (table 6.1) after 14 days, blinatumomab will be infused at a target dose of at 112mcg/d for 28 days. Subjects will be restaged after a 6 week treatment free period by PET CT. All subjects without disease progression will receive an additional 4 week cycle starting at the target dose of 112 mcg/d. Blinatumomab: Blinatumomab is a bispecific t cell engaging antibody targeting CD19 and CD3 approved for B cell acute lymphoblastic leukemia

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Blinatumomab	Blinatumomab will be administered as a continuous IV infusion through a central venous catheter for a 42 day cycle. Blinatumomab will start with a 7 day infusion at 9mcg/d. If no dose limiting toxicity (table 6.1) after 7 days, the dose will be escalated to 28 mcg/d for 7 additional days. If no dose limiting toxicity (table 6.1) after 14 days, blinatumomab will be infused at a target dose of at 112mcg/d for 28 days. Subjects will be restaged after a 6 week treatment free period by PET CT. All subjects without disease progression will receive an additional 4 week cycle starting at the target dose of 112 mcg/d. Blinatumomab: Blinatumomab is a bispecific t cell engaging antibody targeting CD19 and CD3 approved for B cell acute lymphoblastic leukemia

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Response Rate (ORR)

Count of participants achieving a complete or partial response according to the revised response criteria for malignant lymphoma (2014).

A complete response is defined as regression of involved nodes to normal size (1.5 cm or less in their greatest transverse diameter for nodes 1.5 cm or greater before therapy). Involved nodes 1.1 - 1.5 cm in their greatest transverse diameter before treatment must have decreased to less than 1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). For a complete response, the spleen, if enlarged before therapy on a CT scan, must also have regressed in size and must not be palpable.

A partial response is defined as 50% or greater decrease in SPD of up to 6 largest dominant masses. There must also be no new sites of disease or increases in the size of the other nodes, liver, or spleen. Splenic/hepatic nodules must regress by at least 50% in SPD.

Posted

Count of Participants

Participants

at completion of treatment (6 months)

ID	Title	Description
OG000

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Blinatumomab	Blinatumomab will be administered as a continuous IV infusion through a central venous catheter for a 42 day cycle. Blinatumomab will start with a 7 day infusion at 9mcg/d. If no dose limiting toxicity (table 6.1) after 7 days, the dose will be escalated to 28 mcg/d for 7 additional days. If no dose limiting toxicity (table 6.1) after 14 days, blinatumomab will be infused at a target dose of at 112mcg/d for 28 days. Subjects will be restaged after a 6 week treatment free period by PET CT. All subjects without disease progression will receive an additional 4 week cycle starting at the target dose of 112 mcg/d. Blinatumomab: Blinatumomab is a bispecific t cell engaging antibody targeting CD19 and CD3 approved for B cell acute lymphoblastic leukemia

ID	Term
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma

ID	Term
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases