Safety/Efficacy of MEDI-551 in Combination With Immunomod... | NCT02271945

Label	Type	Description	Intervention Names
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Experimental	Participants will receive intravenous (IV) infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.	Drug: MEDI-551 12 mg/kg Drug: MEDI0680 2.5 mg/kg
MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Experimental	Participants will receive IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.	Drug: MEDI-551 12 mg/kg Drug: MEDI0680 10 mg/kg

Name	Type	Description	Arm Group Labels	Other Names
MEDI-551 12 mg/kg	Drug	Participants will receive intravenous (IV) infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Tolerated Dose (MTD) of MEDI-551	The Maximum Tolerated Dose, defined as the highest dose where less than or equal to (<= 1) out of 6 subjects experiences a dose limiting toxicity (DLT) during the DLT evaluation period (Day 1 to Day 28 of Cycle 1) or the highest protocol specified dose not exceeding MTD.	Day 1 to Day 28 of Cycle 1 (28-day cycle)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs)	An Adverse Event (AE) is any unfavourable and unintended signs, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. SAE is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 90 days after the end of treatment (EOT).	From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities	An abnormal laboratory findings that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the end of study drug.	From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities	Vital signs included parameters such as blood pressure, temperature, respiratory rate, and pulse oximetry. An abnormal vital signs and physical findings that was judged by the investigator to be medically significant was reported an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the end of study treatment.

Secondary Outcomes

Measure	Description	Time Frame
Mean Peak and Trough Concentrations of MEDI551	The mean peak and Trough concentration of MEDI551 were observed. Peak is the end of infusion measurement and the Trough is the pre-dose measurement.	End of Infusion (EOI) of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1
Mean Peak and Trough Concentrations of MEDI0680

Eligibility Module

Eligibility Criteria

Key inclusion criteria:

Histologically confirmed aggressive diffuse large B-cell lymphoma (DLBCL), including follicular lymphoma (FL) transforming to DLBCL, transformed indolent lymphoma, mantle cell lymphoma (MCL), or Grade 3B FL for dose-escalation cohorts. Only participants with DLBCL will be enrolled in the dose-expansion cohort.
Willing to provide a fresh tumor sample
Evaluable/measurable disease with measurable disease defined as greater than or equal to (>= 1) lesion less than or equal to (<=) 20 mm in one dimension or ≥ 15 mm in 2 dimensions as measured by conventional or high-resolution (spiral) computed tomography (CT). Disease evaluable by the International Working Group criteria (Cheson et al, 2007). (NOTE: Irradiated lesions will not be evaluable.)
Baseline fludeoxyglucose positron emission tomography (FDG-PET) or FDG-PET/CT scans must show positive lesions compatible with CT-defined anatomical tumor sites.
Relapsed from or refractory to >= 2 prior chemotherapy regimens with >= 1 regimen containing rituximab or failed 1 prior rituximab-containing regimen and unable to tolerate additional multiagent chemotherapy. NOTE: Subjects enrolled in the dose-escalation portion of the study must have exhausted all available standard therapy.
At least 100 days past autologous stem cell transplant (ASCT).
At least 1 year past allogeneic stem-cell transplant (SCT) and off immunosuppression therapy, with no evidence of graft-versus-host disease.
Eastern Cooperative Oncology Group performance status 0-2.
Adequate hematological function
Adequate organ function
Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception for 30 days prior to the first dose of investigational product, and must agree to continue using such precautions for 180 days after the final dose of investigational product.
Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1through 90 days after receipt of the final dose of investigational product.

Key exclusion criteria:

Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for treatment of cancer.
Receipt of any experimental therapy, mAb, cancer vaccine, chemotherapy or small molecule within 28 days prior to Cycle 1 Day 1 or 5 half-lives of that therapy, whichever is shorter.
Previous therapy directed against cluster of differentiation 19 (CD19)
Prior exposure to immunotherapy such as but not limited to other anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), anti-PD 1, or anti-PD-L1 antibodies excluding cancer vaccines.
Vaccination with a live virus within 28 days prior to receiving the first dose of study drug
History of other invasive malignancy within 2 years except for cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has been surgically cured.
Evidence of significant active infection requiring antimicrobial, antifungal, antiparasitic, or antiviral therapy or for which other supportive care is given unless the subject is clinically stable.
Human immunodeficiency virus (HIV) positive serology or acquired immunodeficiency syndrome (AIDS).
Active hepatitis B
Ongoing >= Grade 2 toxicities from previous cancer therapies or any unresolved > Grade 1 immune-related adverse event (irAE) event unless specifically allowed in the inclusion/exclusion criteria.
No immunosuppressive therapy within 14 days of Cycle 1 Day 1 of MEDI0680 (AMP-514) dosing.
Active or prior documented autoimmune or inflammatory disease except vitiligo.
History of primary immunodeficiency.
Major surgical procedures (as defined by the principal investigator) within 28 days of Cycle 1 Day 1 or still recovering from prior surgery.
History of tuberculosis, including those who may have completed prophylactic isoniazid (INH) therapy.
Documented current central nervous system (CNS) involvement, leptomeningeal disease, or spinal cord compression.
Pregnancy or lactation.
Clinically significant abnormality on electrocardiogram (ECG).
Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs from MEDI-551 or MEDI0680 (AMP-514), or compromise the ability of the subject to give written informed consent.

Name	Affiliation	Role
MedImmune LLC	MedImmune LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Birmingham	Alabama	36294-3300	United States
Research Site

ID	Title	Description
FG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
FG001

ID	Title	Description
BG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
BG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
BG002	TOTAL	Total of all reporting groups

Units	Counts
Participants	BG0005 BG0015 BG00210

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

Maximum Tolerated Dose (MTD) of MEDI-551

The Maximum Tolerated Dose, defined as the highest dose where less than or equal to (<= 1) out of 6 subjects experiences a dose limiting toxicity (DLT) during the DLT evaluation period (Day 1 to Day 28 of Cycle 1) or the highest protocol specified dose not exceeding MTD.

Evaluable Population for DLT included all participants in the dose escalation portion who received all protocol assigned doses and completed safety follow-up during the first 28-day period of therapy, or experienced a DLT during the DLT evaluation period.

Posted

Number

mg/kg

Day 1 to Day 28 of Cycle 1 (28-day cycle)

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Units	Counts
Participants	OG0003 OG0014

Title

Denominators

Categories

Title	Measurements
	OG000NAThe study was terminated before the MTD was reached. OG001NAThe study was terminated before the MTD was reached.

Primary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs)

An Adverse Event (AE) is any unfavourable and unintended signs, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. SAE is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 90 days after the end of treatment (EOT).

As-treated Population included all participants who were treated with study drug.

Posted

Count of Participants

Participants

From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Primary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities

An abnormal laboratory findings that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the end of study drug.

As-treated Population included all participants who were treated with study drug.

Posted

Count of Participants

Participants

From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Primary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities

Vital signs included parameters such as blood pressure, temperature, respiratory rate, and pulse oximetry. An abnormal vital signs and physical findings that was judged by the investigator to be medically significant was reported an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the end of study treatment.

As-treated Population included all participants who were treated with study drug.

Posted

Count of Participants

Participants

From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Primary

Number of Participants With Best Overall Response

The best overall response was calculated, based upon the disease assessments recorded during the study visits, and summarized with the number of participants for the following categories: complete response (disappearance of all evidence of disease), partial response (regression of measurable disease and no new sites), stable disease (SD), progessive disease (PD), and non- evaluable (NE).

As-treated Population included all participants who were treated with study drug.

Posted

Count of Participants

Participants

Day 1 to Day 28 of Cycle 13 (28-day cycle)

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Secondary

Mean Peak and Trough Concentrations of MEDI551

The mean peak and Trough concentration of MEDI551 were observed. Peak is the end of infusion measurement and the Trough is the pre-dose measurement.

As-treated Population included all participants who were treated with study drug.

Posted

Mean

Standard Deviation

mcg/mL

End of Infusion (EOI) of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Units	Counts
Participants

Secondary

Mean Peak and Trough Concentrations of MEDI0680

The mean peak and Trough concentration of MEDI0680 were observed. Peak is the end of infusion measurement and the Trough is the pre-dose measurement.

As-treated Population included all participants who were treated with study drug.

Posted

Mean

Standard Deviation

mcg/mL

EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Units	Counts
Participants

Secondary

Terminal Half-Life (t1/2) of MEDI551

Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.

As-treated Population included all participants who were treated with study drug.

Posted

Mean

Full Range

EOI of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Units	Counts
Participants

Secondary

Terminal Half-Life (t1/2) of MEDI0680

Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.

As-treated Population included all participants who were treated with study drug.

Posted

Median

Full Range

EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Units	Counts
Participants

Secondary

Number of Participants With Positive Anti-Drug Antibodies (ADA) for MEDI-551 and MEDI0680

A participant was considered ADA-positive across the study if they had a positive reading (titer of 50 or higher) at any time point during the study.

As-treated Population included all participants who were treated with study drug.

Posted

Number

Participants

30 min prior to infusion of MEDI-551 on Day 1 of Cycles 1, 2, 6, 9, and 12 and up to 90-days after last dose of study drug (up to approximately 2 years)

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Units	Counts

Secondary

Duration of Complete Response

Duration of Complete Response defined as time from start of first documented Complete Response [CR] to the time of disease progression or death, whichever occurs first. Only participants who have achieved complete response assessed by investigator were evaluated.

As-treated Population included all participants who were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.

Posted

From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Secondary

Number of Participants With Disease Control

Disease control includes CR (disappearance of all evidence of disease), PR (regression of measurable disease and no new sites), or SD for at least 8 weeks.

As-treated Population included all participants who were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.

Posted

From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Units	Counts

Secondary

Duration of Disease Control

Duration of disease control is defined as the time period from the start of disease control event to the event of disease progression.

As-treated Population included all participants who were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.

Posted

From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Units	Counts
Participants

Secondary

Progression-free Survival (PFS)

Progression-free survival (PFS) is defined as the time from the start of study drug administration until the first documentation of disease progression or death due to any cause, whichever occurs first.

As-treated Population included all participants who were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.

Posted

From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Units	Counts

Secondary

Overall Survival (OS)

Overall survival defined as the time from the start of study drug administration until death due to any cause.

As-treated Population included all participants who were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.

Posted

From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Units	Counts
Participants

Secondary

Time to Response (TTR)

Time to response (TTR) defined as the time from the start of study drug administration until the first documentation of disease response. Only participants who have achieved objective response (confirmed CR or confirmed PR) assessed by investigator were evaluated for TTR.

As-treated Population included all participants who were treated with study drug. This parameter was not analyzed as study was discontinued before sufficient data could be collected.

Posted

From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)

ID	Title	Description
OG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
OG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypoglobulinaemia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Vision blurred	Eye disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Constipation	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected5 at risk EG0011 events1 affected5 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0003 events2 affected5 at risk EG0010 events0 affected5 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected5 at risk EG0011 events1 affected5 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 events1 affected5 at risk EG0011 events1 affected5 at risk
Chills	General disorders	MedDRA 19.0	Systematic Assessment	EG0002 events1 affected5 at risk EG0011 events1 affected5 at risk
Fatigue	General disorders	MedDRA 19.0	Systematic Assessment	EG0003 events2 affected5 at risk EG0013 events3 affected5 at risk
Oedema peripheral	General disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected5 at risk EG0011 events1 affected5 at risk
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Device related infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Sinusitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0015 events2 affected5 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Blood pressure increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Lymphocyte count decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0014 events2 affected5 at risk
Neutrophil count decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Platelet count decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
White blood cell count decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0012 events2 affected5 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0012 events2 affected5 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Vitamin b12 deficiency	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected5 at risk
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Dizziness	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Headache	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Paraesthesia	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected5 at risk EG0011 events1 affected5 at risk
Sciatica	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Anxiety	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0012 events1 affected5 at risk
Depression	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected5 at risk EG0011 events1 affected5 at risk
Insomnia	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Stress	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Haematuria	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Proteinuria	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Bronchiectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0013 events2 affected5 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected5 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0014 events1 affected5 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0006 events2 affected5 at risk EG0010 events0 affected5 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Flushing	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk

ID	Term
D012008	Recurrence
D008228	Lymphoma, Non-Hodgkin

ID	Term
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.	3	5	2	5	5	5
EG001	MEDI-551 12 mg/kg and MEDI0680 10 mg/kg	Participants received IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.	3	5	1	5	5	5

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk
Blood creatinine increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk
Diffuse large b-cell lymphoma recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk