A Clinical Study Using MEDI-551 in Adult Participants With Relapsed or Refractory Advanced B-Cell Malignancies

Brief Summary

The purpose of this study is to determine the maximum tolerated dose of this drug (MEDI-551) in participants with advanced B-cell malignancies. Expansion to occur at maximum tolerated dose (MTD), or if not reached, at optimal biologic dose (OBD).

Brief Title

Detailed Description

To determine the MTD or OBD of MEDI-551 in participants with relapsed or refractory advanced B-cell malignancies.

Categories

Cancer

Completion Date

2019-03-21

Completion Date Type

Actual

Conditions

B-cell Malignancies

Cancer

Eligibility Criteria

Inclusion Criteria:

* Histologically confirmed CLL, DLBCL, FL, or MM;
* Karnofsky Performance Status \>= 70;
* Life expectancy of \>= 12 weeks;
* Prior radiation therapy provided exposure does not exceed an area of 25% of marrow space
* Adequate hematological function
* Adequate organ function

Exclusion Criteria:

* Any available standard line of therapy known to be life-prolonging or life-saving;
* No concurrent therapy or therapy within six weeks of first dose of MEDI-551 for treatment of cancer
* Previous therapy directed against CD19
* Vaccination (other than experimental cancer vaccine therapy) within 28 days prior to receiving the first dose of MEDI-551;
* History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured;
* Active infection requiring treatment
* Autologous stem cell transplantation within 4 months prior to study entry;
* Allogeneic stem cell transplantation or any other organ transplant;
* Ongoing \>= Grade 2 toxicities from previous cancer therapies unless specifically allowed in the Inclusion/Exclusion criteria.
* Use of immunosuppressive medication other than steroids within 28 days before the first dose of MEDI-551;
* Use of immunosuppressive medication other than steroids within 28 days before the first dose of MEDI-551 (inhaled and topical corticosteroids are permitted);
* Documented current central nervous system involvement by leukemia or lymphoma;
* Pregnancy or lactation;
* Clinically significant abnormality on ECG.

Inclusion Criteria

Inclusion Criteria:

* Histologically confirmed CLL, DLBCL, FL, or MM;
* Karnofsky Performance Status \>= 70;
* Life expectancy of \>= 12 weeks;
* Prior radiation therapy provided exposure does not exceed an area of 25% of marrow space
* Adequate hematological function
* Adequate organ function

Inclusion/

Gender

All

Gender Based

false

Keywords

Cancer

Healthy Volunteers

No

Last Update Post Date

Wed, 05/13/2020 - 12:00

Last Update Post Date Type

Actual

Last Update Submit Date

Wed, 04/29/2020 - 12:00

Maximum Age

99 Years

Minimum Age

18 Years

NCT Id

NCT00983619

Org Class

Industry

Org Full Name

MedImmune LLC

Org Study Id

MI-CP204

Overall Status

Completed

Phases

Phase 1

Phase 2

Primary Completion Date

Thu, 03/21/2019 - 12:00

Primary Completion Date Type

Actual

Official Title

A Phase 1, Dose-escalation Study of MEDI-551, a Humanized Monoclonal Antibody Directed Against CD19, in Adult Subjects With Relapsed or Refractory Advanced B-Cell Malignancies

Primary Outcomes

Outcome Description

Optimal biologic dose (OBD) was defined as the dose lower than the maximum tolerated dose (MTD), used for dose expansion. The MTD is defined as the highest dose at which less than equal to (\<=) 1 out of 6 participants experience a dose limiting toxicities (DLT) from the time of first administration of MEDI-551 through the first 28-day cycle.

Outcome Measure

Optimal Biologic Dose of MEDI-551 for Part A

Outcome Time Frame

Day 1 to Day 28 of Cycle 1

Outcome Description

Highest protocol-defined dose is dose of MEDI-551 in the absence of exceeding the MTD in participants with relapsed or rituximab-refractory chronic lymphocytic leukemia (defined as those with less than a partial response (PR) or progression within 6 months after completing therapy with rituximab). The MTD is defined as the highest dose at which \<= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.

Outcome Measure

Highest Protocol-defined Dose for Part B

Outcome Time Frame

Day 1 to Day 28 of Cycle 1

Outcome Description

Highest protocol-defined dose is the dose of MEDI-551 in combination with rituximab at the MTD or the highest protocol-defined dose in the absence of exceeding the MTD in participants with aggressive lymphomas. The MTD is defined as the highest dose at which \<= 1 out of 6 participants experience a DLT from the time of first administration of MEDI-551 through the first 28-day cycle.

Outcome Measure

Highest Protocol-defined Dose for Part C

Outcome Time Frame

Day 1 to Day 28 of Cycle 1

Outcome Description

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are 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.

Outcome Measure

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part A, Part B, and Part C

Outcome Time Frame

Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Description

A dose limiting toxicities (DLT) for arm A, B, and C was defined as MEDI-551 (or rituximab for Arm C) treatment-related AE of any toxicity grade that led to an inability to receive a full cycle of MEDI-551 (or rituximab for Arm C) or any Grade 3 or higher toxicity (except Grade 3 fever, transient Grade 3 rigors or chills, Grade 3 tumor lysis syndrome, any Grade 3 or 4 electrolyte alteration, any Grade 3 liver function test elevation,\>= Grade 3 or 4 lymphopenia or leukopenia, \<= Grade 4 neutropenia, \<= Grade 4 thrombocytopenia, \<= Grade 4 anemia, and Grade 3 infusion-related reaction and infusion reaction), during DLT evaluable period.

Outcome Measure

Number of Participants With Dose Limiting Toxicities of MEDI-551 in Part A, Part B, and Part C

Outcome Time Frame

Day 1 to Day 28 of Cycle 1

Outcome Description

Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.

Outcome Measure

Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part A, Part B, and Part C

Outcome Time Frame

Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Description

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure, pulse rate, respiratory rate, and pulse oximetry).

Outcome Measure

Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part A, Part B, and Part C

Outcome Time Frame

Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Description

Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, and QT intervals from the primary lead of the digital 12-lead ECG.

Outcome Measure

Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part A, Part B, and Part C

Outcome Time Frame

Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Description

Complete response (CR) is defined as disappearance of all evidence of disease according to International Working Group criteria (IWG). For nodal masses; fluorodeoxyglucose (FDG)-avid or polyethylene terephthalate (PET) positive prior to therapy; mass of any size permitted if PET negative .Variably FDG-avid or PET negative; regression to normal size on computed tomography (CT). For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry (IHC) was negative.

Outcome Measure

Percentage of Participants With Complete Response for Part B, Part C, and Part D

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Description

The PR is defined as regression of measurable disease and no new sites according to IWG criteria. Nodal masses: \>= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: \>= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.

Outcome Measure

Percentage of Participants With Partial Response for Part B, Part C, and Part D

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Description

Duration of CR is from the first documentation of a CR to the time of progressive disease/relapse according to IWG criteria. The CR is disappearance of all evidence of disease according to IWG criteria. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Kaplan-Meier method was used to evaluate duration of CR.

Outcome Measure

Duration of Complete Response for Part B, Part C, and Part D

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Description

Objective response rate (ORR) is proportion of participants with CR or partial response (PR) as per IWG criteria. CR is disappearance of all evidence of disease. Nodal masses; FDG-avid/PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if unknown by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: \>= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: \>= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.

Outcome Measure

Percentage of Participants With Objective Response Rate for Part B, Part C, and Part D

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Description

Duration of objective response (DOR) is the first documentation of objective response to the first documented progressive disease (PD) or relapse according to IWG criteria. PD is defined as any new lesion or increase by \>=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) \> 1.5 cm in any axis, \>= 50% increase in SPD of more than one node, or \>= 50% increase in longest diameter of a previously identified node \> 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: \> 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate DOR.

Outcome Measure

Duration of Objective Response for Part B, Part C, and Part D

Outcome Time Frame

Cycle 1 Day 1, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Description

Disease control includes CR, PR, or stable disease (SD) for at least 8 weeks according to IWG criteria. The CR is disappearance of all evidence of disease. Nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. Spleen; not palpable, nodules disappeared. Bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. PR is regression of measurable disease and no new sites. Nodal masses: \>= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. Spleen and liver: \>= 50% decrease in SPD of nodules; no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy. SD is failure to attain CR/PR or PD.

Outcome Measure

Percentage of Participants With Disease Control Rate for Part B, Part C, and Part D

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Description

Duration of disease control is defined as the time period from start of MEDI-551 administration to the event of PD/relapse. PD is defined as any new lesion or increase by \>=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) \> 1.5 cm in any axis, \>= 50% increase in SPD of more than one node, or \>= 50% increase in longest diameter of a previously identified node \> 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: \> 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate duration of disease control.

Outcome Measure

Duration of Disease Control for Part B, Part C, and Part D

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Description

Time to response (TTR) is measured from the start of MEDI-551 administration to the first documentation of response (CR or PR) and assessed in participants who have achieved objective response. Kaplan-Meier method was used to evaluate TTR.

Outcome Measure

Time to Response for Part B, Part C, and Part D

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Description

Progression-free survival (PFS) is measured from the start of MEDI-551 treatment until the first documentation of disease progression, relapse or death, whichever occurs first. The PFS was censored on the date of last disease assessment for participants who have no documented PD/relapse or death prior to data cutoff, dropout, or the initiation of alternative anticancer therapy. Kaplan-Meier method was used to evaluate PFS.

Outcome Measure

Progression Free Survival for Part B, Part C, and Part D

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Description

Overall survival (OS) is measured from the start of MEDI-551 treatment until death. For participants who are alive at the end of study or lost to follow-up, OS will be censored on the last date when participants were known to be alive. Kaplan-Meier method was used to evaluate OS.

Outcome Measure

Overall Survival for Part B, Part C, and Part D

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Secondary Ids

Secondary Id

2009-016378-34

Secondary Outcomes

Outcome Description

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are 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.

Outcome Time Frame

Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Measure

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part D

Outcome Description

Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.

Outcome Time Frame

Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Measure

Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part D

Outcome Description

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure, pulse rate, respiratory rate, and pulse oximetry).

Outcome Time Frame

Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Measure

Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part D

Outcome Description

Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, and QT intervals from the primary lead of the digital 12-lead ECG.

Outcome Time Frame

Day 1 through 90-Day Post Last Dose (Approximately 9 years)

Outcome Measure

Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part D

Outcome Description

The CR is defined as disappearance of all evidence of disease according to IWG criteria. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative .Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative.

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure

Percentage of Participants With Complete Response for Part A

Outcome Description

The PR is defined as regression of measurable disease and no new sites according to IWG criteria. Nodal masses: \>= 50% decrease in sum of the product diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. Spleen and liver: \>= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone marrow: irrelevant if positive prior to therapy.

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure

Percentage of Participants With Partial Response for Part A

Outcome Description

Duration of CR is from the first documentation of a CR to the time of progressive disease/relapse according to IWG criteria. The CR is disappearance of all evidence of disease. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. Variably FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. Kaplan-Meier method was used to evaluate duration of CR.

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure

Duration of Complete Response for Part A

Outcome Description

The ORR is defined as proportion of participants with CR or PR according to IWG criteria. CR is disappearance of all evidence of disease. For nodal masses; FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if unknown by morphology, IHC was negative. PR is regression of measurable disease and no new sites. For nodal masses: \>= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) FDG-avid or PET negative; regression on CT. For spleen and liver: \>= 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy.

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure

Percentage of Participants With Objective Response Rate for Part A

Outcome Description

The DOR is the first documentation of objective response to the first documented PD or relapse according to IWG criteria. PD is defined as any new lesion or increase by \>=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) \> 1.5 cm in any axis, \>= 50% increase in SPD of more than one node, or \>= 50% increase in longest diameter of a previously identified node \> 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: \> 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate DOR.

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure

Duration of Objective Response for Part A

Outcome Description

Disease control includes CR, PR, or SD for at least 8 weeks according to IWG criteria. The CR is disappearance of all evidence of disease. For nodal masses; FDG -avid or PET positive prior to therapy; mass of any size permitted if PET negative. FDG-avid or PET negative; regression to normal size on CT. For spleen; not palpable, nodules disappeared. For bone marrow; infiltrate cleared on repeat biopsy; if indeterminate by morphology, IHC was negative. PR is regression of measurable disease and no new sites. For nodal masses: \>= 50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. For spleen and liver: \>= 50% decrease in SPD of nodules; no increase in size of liver or spleen. For bone marrow: irrelevant if positive prior to therapy. SD is failure to attain CR/PR or PD.

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure

Percentage of Participants With Disease Control Rate for Part A

Outcome Description

Duration of disease control is defined as the time period from start of MEDI-551 administration to the event of PD/relapse according to IWG criteria. PD is defined as any new lesion or increase by \>=50% of previously involved sites from nadir. For nodal masses: appearance of a new lesion(s) \> 1.5 cm in any axis, \>= 50% increase in SPD of more than one node, or \>= 50% increase in longest diameter of a previously identified node \> 1 cm in short axis lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. For spleen: \> 50% increase from nadir in the SPD of any previous lesions. For bone marrow: New or recurrent involvement. Kaplan-Meier method was used to evaluate duration of disease control.

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure

Duration of Disease Control for Part A

Outcome Description

The TTR is measured from the start of MEDI-551 administration to the first documentation of response (CR or PR) and assessed in participants who have achieved objective response. Kaplan-Meier method was used to evaluate TTR.

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure

Time to Response for Part A

Outcome Description

The PFS is measured from the start of MEDI-551 treatment until the first documentation of disease progression, relapse or death, whichever occurs first. Kaplan-Meier method was used to evaluate PFS. The PFS was censored on the date of last disease assessment for participants who have no documented PD/relapse or death prior to data cutoff, dropout, or the initiation of alternative anticancer therapy.

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure

Progression Free Survival for Part A

Outcome Description

The OS is measured from the start of MEDI-551 treatment until death. For participants who are alive at the end of study or lost to follow-up, OS will be censored on the last date when participants were known to be alive. Kaplan-Meier method was used to evaluate OS.

Outcome Time Frame

Day 1 of all Cycles, then every 2 months during the first year of treatment and then every 6 months until end of treatment (unacceptable toxicity, disease progression, withdraws consent, whichever occurred first) (approximately 9 years)

Outcome Measure

Overall Survival for Part A

Outcome Description

Trough serum concentration (Ctrough) is defined as lowest concentration reached by a drug before the next dose is administered. The Ctrough concentration of MEDI-551 by treatment cycle is reported.

Outcome Time Frame

For Part A: C1D1 of each cycles; For Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; For Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10;For Part D: C1D1, C1D8, then Day 1 of each cycle until Cycle 10

Outcome Measure

Trough Serum Concentration of MEDI-551 by Treatment Cycle

Outcome Description

Peak serum concentration is concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and before the administration of a second dose.

Outcome Time Frame

For Part A: C1D1 of each cycles; For Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; For Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10;For Part D: C1D1, C1D8, then Day 1 of each cycle until Cycle 10

Outcome Measure

Peak Serum Concentration of MEDI-551 by Treatment Cycle

Outcome Description

Area under the concentration-time curve at steady state (Css, AUC) of MEDI-551 is reported.

Outcome Time Frame

Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24

Outcome Measure

Area Under the Concentration Curve at Steady State (AUCss) of MEDI-551

Outcome Description

Apparent clearance of MEDI-551 is reported.

Outcome Time Frame

Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24

Outcome Measure

Apparent Clearance of MEDI-551

Outcome Description

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Central volume of distribution (Vd1) is defined as hypothetical volume into which a drug initially distributes upon administration and peripheral volume of distribution (Vd2) is defined as the sum of all tissue spaces outside the central compartment.

Outcome Time Frame

Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24

Outcome Measure

Volume of Distribution of MEDI-551

Outcome Description

Terminal half-life is the time required for the plasma concentration of MEDI-551 to fall by 50% during the terminal phase.

Outcome Time Frame

Part A:Cycle(C)1 Day(D)1 (Pre & post dose [PPD] 2,6,24,48 hrs PD); PPD once a week in 4 weeks C till C71; Part B:C1 (D1,D8,D15,D22),PPD of D1 of each C till C28; Part C & D:PPD of C1 (D2,D8), predose D15 and 22, PPD of D1 of each C till C24

Outcome Measure

Terminal Half-life (t1/2) of MEDI-551

Outcome Description

Number of participants with positive Anti-drug antibodies (ADA) titer to MEDI-551 is reported.

Outcome Time Frame

Part A:C1D1; Part B: C1D1; Part C: C1D1; Part D: C1D1; End of treatment (EOT); 90 Days post last dose (approximately 9 years)

Outcome Measure

Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI-551

Outcome Description

B-cell Concentration in serum is reported.

Outcome Time Frame

Part A:C1D1 of each cycles; Part B: C1D1 of each cycle + C1D8, C1D15, and C1D22; Part C: C1D2, C1D8, then Day 1 of each cycle until Cycle 10; Part D: C1D1, C1D8, Day 1 of each cycle until Cycle 10; EOT;90 Days post last dose (approximately 9 years)

Outcome Measure

B-cell Concentration in Serum

Outcome Description

Immunoglobin (Ig) concentration in serum is reported.

Outcome Time Frame

Part A:C1D1 of each cycles; EOT;90 Days post last dose (approximately 9 years)

Outcome Measure

Immunoglobulin (Ig) Concentration in Serum