Clinical trial NCT00983619: A Clinical Study Using MEDI-551 in Adult Participants With Relapsed or Refractory Advanced B-Cell Malignancies
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: B-cell Malignancies
Cancer
Keywords: Cancer
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2009-09-24
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

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.

Primary outcomes:
measure: Optimal Biologic Dose of MEDI-551 for Part A
timeFrame: Day 1 to Day 28 of Cycle 1
measure: Highest Protocol-defined Dose for Part B
timeFrame: Day 1 to Day 28 of Cycle 1
measure: Highest Protocol-defined Dose for Part C
timeFrame: Day 1 to Day 28 of Cycle 1
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
timeFrame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
measure: Number of Participants With Dose Limiting Toxicities of MEDI-551 in Part A, Part B, and Part C
timeFrame: Day 1 to Day 28 of Cycle 1
measure: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part A, Part B, and Part C
timeFrame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part A, Part B, and Part C
timeFrame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
measure: Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part A, Part B, and Part C
timeFrame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
measure: Percentage of Participants With Complete Response for Part B, Part C, and Part D
timeFrame: 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)
measure: Percentage of Participants With Partial Response for Part B, Part C, and Part D
timeFrame: 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)
measure: Duration of Complete Response for Part B, Part C, and Part D
timeFrame: 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)
measure: Percentage of Participants With Objective Response Rate for Part B, Part C, and Part D
timeFrame: 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)
measure: Duration of Objective Response for Part B, Part C, and Part D
timeFrame: 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)
measure: Percentage of Participants With Disease Control Rate for Part B, Part C, and Part D
timeFrame: 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)
measure: Duration of Disease Control for Part B, Part C, and Part D
timeFrame: 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)
measure: Time to Response for Part B, Part C, and Part D
timeFrame: 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)
measure: Progression Free Survival for Part B, Part C, and Part D
timeFrame: 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)
measure: Overall Survival for Part B, Part C, and Part D
timeFrame: 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:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part D
timeFrame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
measure: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part D
timeFrame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part D
timeFrame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
measure: Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part D
timeFrame: Day 1 through 90-Day Post Last Dose (Approximately 9 years)
measure: Percentage of Participants With Complete Response for Part A
timeFrame: 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)
measure: Percentage of Participants With Partial Response for Part A
timeFrame: 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)
measure: Duration of Complete Response for Part A
timeFrame: 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)
measure: Percentage of Participants With Objective Response Rate for Part A
timeFrame: 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)
measure: Duration of Objective Response for Part A
timeFrame: 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)
measure: Percentage of Participants With Disease Control Rate for Part A
timeFrame: 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)
measure: Duration of Disease Control for Part A
timeFrame: 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)
measure: Time to Response for Part A
timeFrame: 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)
measure: Progression Free Survival for Part A
timeFrame: 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)
measure: Overall Survival for Part A
timeFrame: 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)
measure: Trough Serum Concentration of MEDI-551 by Treatment Cycle
timeFrame: 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
measure: Peak Serum Concentration of MEDI-551 by Treatment Cycle
timeFrame: 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
measure: Area Under the Concentration Curve at Steady State (AUCss) of MEDI-551
timeFrame: 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
measure: Apparent Clearance of MEDI-551
timeFrame: 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
measure: Volume of Distribution of MEDI-551
timeFrame: 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
measure: Terminal Half-life (t1/2) of MEDI-551
timeFrame: 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
measure: Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI-551
timeFrame: Part A:C1D1; Part B: C1D1; Part C: C1D1; Part D: C1D1; End of treatment (EOT); 90 Days post last dose (approximately 9 years)
measure: B-cell Concentration in Serum
timeFrame: 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)
measure: Immunoglobulin (Ig) Concentration in Serum
timeFrame: Part A:C1D1 of each cycles; EOT;90 Days post last dose (approximately 9 years)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: La Jolla
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Westwood
country: United States
facility: Research Site
state: Kansas
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: New Brunswick
country: United States
facility: Research Site
state: New Jersey
city: Lake Success
country: United States
facility: Research Site
state: New York
city: Hershey
country: United States
facility: Research Site
state: Pennsylvania
city: Houston
country: United States
facility: Research Site
state: Texas
city: Morgantown
country: United States
facility: Research Site
state: West Virginia
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Gent
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Yvoir
country: Belgium
facility: Research Site
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Cona
country: Italy
facility: Research Site
city: Modena
country: Italy
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Medimmune Inc. Clinical Development
role: STUDY_DIRECTOR
References: