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

NCT00983619 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: MI-CP2042009-016378-34
• Study Type: interventional
• Target: 136
• Locations: 5 countries
• Sites: 21

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).

Conditions

B-cell Malignancies; Cancer

Keywords

Cancer

Outcome Measures

Primary Outcomes (18)

• Optimal Biologic Dose of MEDI-551 for Part A

  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.

  Day 1 to Day 28 of Cycle 1

• Highest Protocol-defined Dose for Part B

  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.

  Day 1 to Day 28 of Cycle 1

• Highest Protocol-defined Dose for Part C

  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.

  Day 1 to Day 28 of Cycle 1

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

  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.

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

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

  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.

  Day 1 to Day 28 of Cycle 1

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

  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.

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

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

  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).

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

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

  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.

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

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

  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.

  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)

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

  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.

  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)

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

  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.

  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)

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

  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.

  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)

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

  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.

  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)

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

  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.

  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)

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

  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.

  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)

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

  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.

  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)

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

  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.

  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)

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

  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.

  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 Outcomes (23)

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

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

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

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

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

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

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

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

• Percentage of Participants With Complete Response for Part A

  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)

Study Arms (12)

Part A-MEDI-551 0.5 mg/kg

EXPERIMENTAL

Participants will receive intravenous (IV) infusion of MEDI 551 0.5 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Drug: MEDI-551

Part A-MEDI-551 1 mg/kg

EXPERIMENTAL

Participants will receive IV infusion of MEDI 551 1 mg/kg once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Drug: MEDI-551

Part A-MEDI-551 2 mg/kg

EXPERIMENTAL

Participants will receive IV infusion of MEDI 551 2 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Drug: MEDI-551

Part A-MEDI-551 4 mg/kg

EXPERIMENTAL

Participants will receive IV infusion of MEDI 551 4 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Drug: MEDI-551

Part A-MEDI-551 8 mg/kg

EXPERIMENTAL

Participants will receive IV infusion of MEDI 551 8 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Drug: MEDI-551

Part A-MEDI-551 12 mg/kg

EXPERIMENTAL

Participants will receive IV infusion of MEDI 551 12 mg/kg on Days 1 and 8 of Cycle 1 (loading doses) and then once every 28 days at the start of each subsequent cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Drug: MEDI-551

Part B-MEDI-551 6 mg/kg

EXPERIMENTAL

Participants will receive IV infusion of MEDI- 551 6 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Drug: MEDI-551

Part B-MEDI-551 12 mg/kg

EXPERIMENTAL

Participants will receive IV infusion of MEDI- 551 12 mg/kg weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and thereafter from Cycle 2 on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Drug: MEDI-551

Part B-MEDI-551 24 mg/kg

EXPERIMENTAL

Participants will receive IV infusion of MEDI- 551 24 mg/kg weekly for 4 weeks during Cycle 1 (over 2 days on Day 1 and Day 2, and on Days 8, 15, and 22) and thereafter from Cycle 2, on Day 1 of each 28-day cycle until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Drug: MEDI-551

Part C-MEDI-551 8 mg/kg + rituximab

EXPERIMENTAL

Participants will receive IV infusion of MEDI- 551 8 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m\^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg will be administered on Day 1 of each 28-day cycle. The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent.

Drug: MEDI-551; Drug: Rituximab

Part C-MEDI-551 12 mg/kg + rituximab

EXPERIMENTAL

Participants will receive IV infusion of MEDI- 551 12 mg/kg on Days 2 and 8 during Cycle 1 and on Day 1 during Cycle 2 (28-day cycle) in combination with rituximab 375 mg/m\^2 on Days 1, 8, 15, and 22. From Cycle 3 onwards, only MEDI- 551 8 mg/kg will be administered on Day 1 of each 28-day cycle. The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent.

Drug: MEDI-551; Drug: Rituximab

Part D-MEDI-551 12 mg/kg

EXPERIMENTAL

Participants will receive IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and thereafter Day 1 of 28- day cycles from Cycle 2 onwards. Treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches CR or withdraws consent.

Drug: MEDI-551

Interventions

MEDI-551 DRUG

MEDI-551 will be administered intravenously (IV) once every week in 4-week cycles until complete response, disease progression, toxicity, or another reason for treatment discontinuation will be observed.

Part A-MEDI-551 0.5 mg/kg; Part A-MEDI-551 1 mg/kg; Part A-MEDI-551 12 mg/kg; Part A-MEDI-551 2 mg/kg; Part A-MEDI-551 4 mg/kg; Part A-MEDI-551 8 mg/kg; Part B-MEDI-551 12 mg/kg; Part B-MEDI-551 24 mg/kg; Part B-MEDI-551 6 mg/kg; Part C-MEDI-551 12 mg/kg + rituximab; Part C-MEDI-551 8 mg/kg + rituximab; Part D-MEDI-551 12 mg/kg

Rituximab DRUG

Rituximab will be administered IV on Days 1, 8, 15, and 22 (28- day cycle). The treatment will be continued until the participants experiences unacceptable toxicity, disease progression, reaches complete response or withdraws consent.

Part C-MEDI-551 12 mg/kg + rituximab; Part C-MEDI-551 8 mg/kg + rituximab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (21)

Research Site

Birmingham, Alabama, 35249, United States

Location

Research Site

La Jolla, California, 92093, United States

Location

Research Site

Washington D.C., District of Columbia, 20007, United States

Location

Research Site

Tampa, Florida, 33612, United States

Location

Research Site

Chicago, Illinois, 60612, United States

Location

Research Site

Westwood, Kansas, 66205, United States

Location

Research Site

Rochester, Minnesota, 55905, United States

Location

Research Site

New Brunswick, New Jersey, 08903, United States

Location

Research Site

Lake Success, New York, 11042, United States

Location

Research Site

Hershey, Pennsylvania, 17033, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Morgantown, West Virginia, 26506, United States

Location

Research Site

Milwaukee, Wisconsin, 53226, United States

Location

Research Site

Ghent, 9000, Belgium

Location

Research Site

Leuven, 3000, Belgium

Location

Research Site

Yvoir, 5530, Belgium

Location

Research Site

Montreal, Quebec, H3T 1E2, Canada

Location

Research Site

Cona, 44124, Italy

Location

Research Site

Modena, 41124, Italy

Location

Research Site

Madrid, 28033, Spain

Location

Research Site

Madrid, 28050, Spain

Location

Related Links

• Click here and search for drug information provided by the FDA.
• Click here to find results for studies related to marketed products.
• Statistical Analysis Plan (SAP)
• MI-CP204 redacted CSP

MeSH Terms

Conditions

Neoplasms

Interventions

inebilizumab; Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Shahram Rahimian
• Organization: MedImmune, LLC

information.center@astrazeneca.com

800-236-9933

Study Officials

• Medimmune Inc. Clinical Development

  MedImmune LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2009
• First Posted: September 24, 2009
• Study Start: April 16, 2010
• Primary Completion: March 21, 2019
• Study Completion: March 21, 2019
• Last Updated: May 13, 2020
• Results First Posted: May 13, 2020

Record last verified: 2020-04

Locations

ES (2); US (13); IT (2); BE (3); CA (1)