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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01466153
First received: September 30, 2011
Last updated: April 20, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Chronic Lymphocytic Leukemia (CLL) Drug: Rituximab Drug: Bendamustine Drug: MEDI-551 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 2 Open-label Study of MEDI-551 and Bendamustine vs Rituximab and Bendamustine in Adults With Relapsed or Refractory CLL

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Objective Response Rate [ 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) ]
    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) [ Time Frame: From time of consent to 90 days post last dose ]
    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 [ Time Frame: From time of consent to 90 days post last dose ]
    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 [ Time Frame: From time of consent to 90 days post last dose ]
    AEs observed in participants with clinically significant ECG abnormalities were assessed.

  • Complete Response Rate [ 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) ]
    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 [ 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) ]
    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 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) ]
    Time to response was evaluated using the Kaplan-Meier method.

  • Time to Disease Progression (TTP) [ 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) ]
    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) [ 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) ]
    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) [ 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) ]
    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) [ 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) ]
    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 [ Time Frame: Pre-infusion and 1 hour post infusion on Days 2 and 8, Days 15 and 22 of cycle 1 ]
    Terminal phase elimination half-life (T1/2) was the time required for half of the drug to be eliminated from the serum.


Enrollment: 183
Study Start Date: February 7, 2012
Study Completion Date: January 8, 2016
Primary Completion Date: January 8, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rituximab + Bendamustine
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.
Drug: Rituximab
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
Other Name: Rituxan; MabThera
Drug: Bendamustine
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.
Experimental: MEDI-551 2 mg/kg + Bendamustine
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.
Drug: Bendamustine
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.
Drug: MEDI-551
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.
Experimental: MEDI-551 4 mg/kg + Bendamustine
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.
Drug: Bendamustine
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.
Drug: MEDI-551
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.

  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01466153

  Show 54 Study Locations
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: MedImmune MedImmune LLC
  More Information

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01466153     History of Changes
Other Study ID Numbers: CD-ON-MEDI-551-1019
Study First Received: September 30, 2011
Results First Received: April 20, 2017
Last Updated: April 20, 2017

Keywords provided by MedImmune LLC:
Chronic lymphocytic leukemia; leukemia; B-Cell malignancy; anti-CD19; monoclonal antibody; CLL; Refractory; Relapse; Non-Hodgkin's Lymphoma

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2017