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A Phase 2, Multicenter, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Primary Purpose

Chronic Lymphocytic Leukemia (CLL)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Rituximab
Bendamustine
MEDI-551
Sponsored by
MedImmune LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia (CLL) focused on measuring Chronic lymphocytic leukemia; leukemia; B-Cell malignancy; anti-CD19; monoclonal antibody; CLL; Refractory; Relapse; Non-Hodgkin's Lymphoma

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed B-cell Chronic Lymphocytic Leukemia (CLL) according to the National Cancer Institute criteria; Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2; Adequate hematological function

Exclusion Criteria:

  • Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational, or hormonal therapy for treatment of lymphoma within 28 days prior to treatment;
  • Exposure to bendamustine within the 180 days before study enrollment
  • Prior autologous or allogeneic stem cell transplantation (SCT);
  • Clinically significant abnormality on electrocardiogram (ECG) as determined by the treating physician or medical monitor;
  • History of other invasive malignancy within 5 years except for localized/in situ carcinomas;
  • Evidence of active infection, Confirmed current central nervous system involvement by leukemia or lymphoma;

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

Rituximab + Bendamustine

MEDI-551 2 mg/kg + Bendamustine

MEDI-551 4 mg/kg + Bendamustine

Arm Description

Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.

MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.

MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.

Outcomes

Primary Outcome Measures

Objective Response Rate
ORR, defined as the proportion of participants with complete response (CR) or partial response (PR) out of total number of participants. Responses were assessed by using National Cancer Institute - Working Group guidelines on CLL.

Secondary Outcome Measures

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs)
An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug (MEDI-551). A serious adverse event (SAE) was 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; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 90 that were absent before treatment or that worsened relative to pre-treatment state. An AESIs was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator to the sponsor. Treatment emergent AESIs were collected from the time of dosing through Day 90 after the last dose of study drug.Hepatic function abnormality and infusion reactions resulting in discontinuation were considered as AESIs.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as AEs
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.
Number of Participants With Abnormal Vital Signs and Electrocardiogram Reported as AEs
AEs observed in participants with clinically significant ECG abnormalities were assessed.
Complete Response Rate
Complete response was as per IWG was the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
Minimal Residual Disease Negative Complete Response (CR) Rate
The MRD-negative CR rate was defined as the percentage of participants who achieved CR and became MRD-negative as determined by flow cytometry. CR as per International Working Group (IWG) was complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
Time to Response
Time to response was evaluated using the Kaplan-Meier method.
Time to Disease Progression (TTP)
TTP was defined as the time from onset of treatment with study drug until first evidence/diagnosis of progressive disease or - in the absence of any diagnosis of progressive disease - until the participant´s death.
Progression Free Survival (PFS)
PFS was measured from the start of treatment with study drug until the first documentation of disease progression or death due to any cause, whichever occurred first. Kaplan-Meier method was used for evaluation.
Overall Survival (OS)
OS was determined as the time from the start of treatment with study drug until death due to any cause. For participants who were alive at the end of the study or lost to follow-up, OS was censored on the last date when the participant was known be alive. Kaplan-Meier method was used for evaluation.
Number of Participants Who Developed Detectable Anti-drug Antibodies (ADA)
A participant was considered ADA-positive across the study if they had a positive reading at any time point during the study.
Terminal Half Life (t1/2) of MEDI-551
Terminal phase elimination half-life (T1/2) was the time required for half of the drug to be eliminated from the serum.

Full Information

First Posted
September 30, 2011
Last Updated
April 20, 2017
Sponsor
MedImmune LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01466153
Brief Title
A Phase 2, Multicenter, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Official Title
A Phase 2 Open-label Study of MEDI-551 and Bendamustine vs Rituximab and Bendamustine in Adults With Relapsed or Refractory CLL
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
February 7, 2012 (undefined)
Primary Completion Date
January 8, 2016 (Actual)
Study Completion Date
January 8, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The overall purpose of the study was to determine if MEDI-551, when used in combination with salvage chemotherapy (bendamustine) in participants with relapsed or refractory CLL who are not eligible for Autologous Stem Cell Transplant (ASCT), had superior efficacy compared to rituximab in the same population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia (CLL)
Keywords
Chronic lymphocytic leukemia; leukemia; B-Cell malignancy; anti-CD19; monoclonal antibody; CLL; Refractory; Relapse; Non-Hodgkin's Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
183 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rituximab + Bendamustine
Arm Type
Active Comparator
Arm Description
Rituximab was administered by IV infusion as 375 mg/m^2 on Day 2 of Cycle 1 and then 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.
Arm Title
MEDI-551 2 mg/kg + Bendamustine
Arm Type
Experimental
Arm Description
MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
Arm Title
MEDI-551 4 mg/kg + Bendamustine
Arm Type
Experimental
Arm Description
MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan; MabThera
Intervention Description
Rituximab was administered by IV infusion as a dose of 375 mg/m^2 on Day 2 of Cycle 1 and then at 500 mg/m^2 on Day 1 of up to 5 subsequent 28-day cycles
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Intervention Description
Bendamustine was administered by IV infusion as a dose of 70 mg/m^2 on Day 1 and Day 2 of each 5 subsequent 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
MEDI-551
Intervention Description
MEDI-551 was administered at 2 mg/kg or 4 mg/kg by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycles.
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
ORR, defined as the proportion of participants with complete response (CR) or partial response (PR) out of total number of participants. Responses were assessed by using National Cancer Institute - Working Group guidelines on CLL.
Time Frame
From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs)
Description
An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug (MEDI-551). A serious adverse event (SAE) was 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; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 90 that were absent before treatment or that worsened relative to pre-treatment state. An AESIs was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator to the sponsor. Treatment emergent AESIs were collected from the time of dosing through Day 90 after the last dose of study drug.Hepatic function abnormality and infusion reactions resulting in discontinuation were considered as AESIs.
Time Frame
From time of consent to 90 days post last dose
Title
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as AEs
Description
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.
Time Frame
From time of consent to 90 days post last dose
Title
Number of Participants With Abnormal Vital Signs and Electrocardiogram Reported as AEs
Description
AEs observed in participants with clinically significant ECG abnormalities were assessed.
Time Frame
From time of consent to 90 days post last dose
Title
Complete Response Rate
Description
Complete response was as per IWG was the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
Time Frame
From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)
Title
Minimal Residual Disease Negative Complete Response (CR) Rate
Description
The MRD-negative CR rate was defined as the percentage of participants who achieved CR and became MRD-negative as determined by flow cytometry. CR as per International Working Group (IWG) was complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
Time Frame
From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)
Title
Time to Response
Description
Time to response was evaluated using the Kaplan-Meier method.
Time Frame
From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)
Title
Time to Disease Progression (TTP)
Description
TTP was defined as the time from onset of treatment with study drug until first evidence/diagnosis of progressive disease or - in the absence of any diagnosis of progressive disease - until the participant´s death.
Time Frame
From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)
Title
Progression Free Survival (PFS)
Description
PFS was measured from the start of treatment with study drug until the first documentation of disease progression or death due to any cause, whichever occurred first. Kaplan-Meier method was used for evaluation.
Time Frame
From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)
Title
Overall Survival (OS)
Description
OS was determined as the time from the start of treatment with study drug until death due to any cause. For participants who were alive at the end of the study or lost to follow-up, OS was censored on the last date when the participant was known be alive. Kaplan-Meier method was used for evaluation.
Time Frame
From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)
Title
Number of Participants Who Developed Detectable Anti-drug Antibodies (ADA)
Description
A participant was considered ADA-positive across the study if they had a positive reading at any time point during the study.
Time Frame
From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)
Title
Terminal Half Life (t1/2) of MEDI-551
Description
Terminal phase elimination half-life (T1/2) was the time required for half of the drug to be eliminated from the serum.
Time Frame
Pre-infusion and 1 hour post infusion on Days 2 and 8, Days 15 and 22 of cycle 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed B-cell Chronic Lymphocytic Leukemia (CLL) according to the National Cancer Institute criteria; Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2; Adequate hematological function Exclusion Criteria: Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational, or hormonal therapy for treatment of lymphoma within 28 days prior to treatment; Exposure to bendamustine within the 180 days before study enrollment Prior autologous or allogeneic stem cell transplantation (SCT); Clinically significant abnormality on electrocardiogram (ECG) as determined by the treating physician or medical monitor; History of other invasive malignancy within 5 years except for localized/in situ carcinomas; Evidence of active infection, Confirmed current central nervous system involvement by leukemia or lymphoma;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MedImmune
Organizational Affiliation
MedImmune LLC
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
Research Site
City
Burbank
State/Province
California
Country
United States
Facility Name
Research Site
City
La Jolla
State/Province
California
Country
United States
Facility Name
Research Site
City
Palm Springs
State/Province
California
Country
United States
Facility Name
Research Site
City
Skokie
State/Province
Illinois
Country
United States
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City
Shreveport
State/Province
Louisiana
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
Country
United States
Facility Name
Research Site
City
Fargo
State/Province
North Dakota
Country
United States
Facility Name
Research Site
City
Dayton
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Newark
State/Province
Ohio
Country
United States
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City
Watertown
State/Province
South Dakota
Country
United States
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Research Site
City
Lubbock
State/Province
Texas
Country
United States
Facility Name
Research Site
City
Morgantown
State/Province
West Virginia
Country
United States
Facility Name
Research Site
City
Antwerpen
Country
Belgium
Facility Name
Research Site
City
Arlon
Country
Belgium
Facility Name
Research Site
City
Kortrijk
Country
Belgium
Facility Name
Research Site
City
Mons
Country
Belgium
Facility Name
Research Site
City
Wilrijk
Country
Belgium
Facility Name
Research Site
City
Yvoir
Country
Belgium
Facility Name
Research Site
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Research Site
City
Greenfield Park
State/Province
Quebec
Country
Canada
Facility Name
Research Site
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Research Site
City
Amiens
Country
France
Facility Name
Research Site
City
Bayonne
Country
France
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Research Site
City
Bordeaux
Country
France
Facility Name
Research Site
City
Le Mans
Country
France
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Research Site
City
Libourne Cedex
Country
France
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Research Site
City
Marseille
Country
France
Facility Name
Research Site
City
Nimes
Country
France
Facility Name
Research Site
City
Dortmund
Country
Germany
Facility Name
Research Site
City
Essen
Country
Germany
Facility Name
Research Site
City
Freiburg
Country
Germany
Facility Name
Research Site
City
Muenchen
Country
Germany
Facility Name
Research Site
City
Wuerzburg
Country
Germany
Facility Name
Research Site
City
Haifa
Country
Israel
Facility Name
Research Site
City
Ramat Gan
Country
Israel
Facility Name
Research Site
City
Bari
Country
Italy
Facility Name
Research Site
City
Lecce
Country
Italy
Facility Name
Research Site
City
Meldola
Country
Italy
Facility Name
Research Site
City
Milano
Country
Italy
Facility Name
Research Site
City
Modena
Country
Italy
Facility Name
Research Site
City
Napoli
Country
Italy
Facility Name
Research Site
City
Orbassano
Country
Italy
Facility Name
Research Site
City
Palermo
Country
Italy
Facility Name
Research Site
City
Pisa
Country
Italy
Facility Name
Research Site
City
Ravenna
Country
Italy
Facility Name
Research Site
City
Rimini
Country
Italy
Facility Name
Research Site
City
Roma
Country
Italy
Facility Name
Research Site
City
San Giovanni Rotondo
Country
Italy
Facility Name
Research Site
City
Torino
Country
Italy
Facility Name
Research Site
City
Udine
Country
Italy
Facility Name
Research Site
City
Gdynia
Country
Poland
Facility Name
Research Site
City
Warszawa
Country
Poland

12. IPD Sharing Statement

Learn more about this trial

A Phase 2, Multicenter, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

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